fluorouracil and Carcinoma, Squamous Cell of Head and Neck

fluorouracil has been researched along with Carcinoma, Squamous Cell of Head and Neck in 174 studies

Fluorouracil: A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.
5-fluorouracil : A nucleobase analogue that is uracil in which the hydrogen at position 5 is replaced by fluorine. It is an antineoplastic agent which acts as an antimetabolite - following conversion to the active deoxynucleotide, it inhibits DNA synthesis (by blocking the conversion of deoxyuridylic acid to thymidylic acid by the cellular enzyme thymidylate synthetase) and so slows tumour growth.

Research

Studies (174)

Authors

Clinical Trials (34)

Trial Overview

Trial Outcomes

Number of Participants Experiencing an Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants that experienced at least one AE was reported for each treatment arm. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

Number of Participants Who Discontinued Study Drug Due to an AE

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants that discontinued study drug due to an AE was reported for each treatment arm. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

Pembro Combo vs Control: Change From Baseline to Week 15 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score

"The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question How would you rate your overall health during the past week? (Item 29) and the Quality of Life (QoL) question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 15 in the GHS/QoL combined score was compared between all participants of the pembro combo arm and the control arm as a pre-specified secondary analysis. As specified by the protocol, change from baseline to Week 15 in the GHS/QoL combined score was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record." (NCT02358031)
Timeframe: Baseline, Week 15

Pembro Combo vs Control: Objective Response Rate (ORR) Per RECIST 1.1 by BICR in All Participants

ORR was defined as the percentage of participants in the analysis population who have a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR for all participants in the pembro combo arm and control arm. Per protocol, ORR was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

Pembro Combo vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1

ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR for all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro combo arm and control arm. Per protocol, ORR was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

Pembro Combo vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20

ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR for all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro combo arm and control arm. Per protocol, ORR was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

Pembro Combo vs Control: OS in Participants With PD-L1 CPS ≥1

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥1. Per protocol, OS was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

Pembro Combo vs Control: OS in Participants With PD-L1 CPS ≥20

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥20. Per protocol, OS was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

Pembro Combo vs Control: Overall Survival (OS) in All Participants

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro combo arm and control arm. Per protocol, OS was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among All Participants

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here out of all participants in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record." (NCT02358031)
Timeframe: Month 12

Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record." (NCT02358031)
Timeframe: Month 12

Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record." (NCT02358031)
Timeframe: Month 12

Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among All Participants

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here out of all participants in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record." (NCT02358031)
Timeframe: Month 6

Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record." (NCT02358031)
Timeframe: Month 6

Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record." (NCT02358031)
Timeframe: Month 6

Pembro Combo vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by IHC as Combined Positive Score ≥20 (hereafter referred to as CPS ≥20). Per protocol, PFS was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record." (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

Pembro Combo vs Control: PFS Per RECIST 1.1 by BICR in Participants With Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by immunohistochemistry (IHC) as Combined Positive Score ≥1 (hereafter referred to as CPS ≥1). Per protocol, PFS was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record." (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

Pembro Combo vs Control: Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in All Participants

"PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the Intent-To-Treat (ITT) population. PFS is reported here for all participants in the pembro combo arm and control arm. Per protocol, PFS was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record." (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

Pembro Combo vs Control: Time to Deterioration (TTD) in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score (Kaplan-Meier Method)

"EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to the GHS question How would you rate your overall health during the past week? (Item 29) and the QoL question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. TTD in GHS/QoL defined as the time from baseline to the first onset of a ≥10 point decrease from baseline in GHS/QoL combined score, with confirmation. Per protocol, TTD in GHS/QoL combined score was compared between all participants of pembro combo arm and control arm as a pre-specified secondary analysis. Also per protocol, TTD in GHS/QoL combined score was compared separately between all participants of pembro mono arm and control arm and is presented later in the record." (NCT02358031)
Timeframe: Baseline up to approximately 12 months

Pembro Combo vs Control: TTD in the EORTC QLQ- H&N35 Swallowing Score (Kaplan-Meier Method)

EORTC QLQ-H&N35 is a 35-item questionnaire developed to assess QoL of head and neck cancer participants and consists of 7 multi-item scales that assess pain, swallowing, senses, speech, social eating, social contact and sexuality. Participant responses to the Swallowing scale (Items 35-38) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. TTD in EORTC QLQ-H&N35 Swallowing Score defined as the time from baseline to the first onset of a ≥10 point decrease from baseline, with confirmation. Per protocol, TTD in EORTC QLQ-H&N35 Swallowing Score was compared between all participants of pembro combo arm and control arm as a pre-specified secondary analysis. Also per protocol, TTD in EORTC QLQ-H&N35 Swallowing Score was compared separately between all participants of pembro mono arm and control arm and is presented later in the record. (NCT02358031)
Timeframe: Baseline up to approximately 12 months

Pembro Combo vs Control: TTD in the EORTC QLQ- Head and Neck Module 35 (H&N35) Pain Score (Kaplan-Meier Method)

EORTC QLQ-H&N35 is a 35-item questionnaire developed to assess QoL of head and neck cancer participants and consists of 7 multi-item scales that assess pain, swallowing, senses, speech, social eating, social contact and sexuality. Participant responses to the Pain scale (Items 31-34) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. TTD in EORTC QLQ-H&N35 Pain Score defined as the time from baseline to the first onset of a ≥10 point decrease from baseline, with confirmation. Per protocol, TTD in EORTC QLQ-H&N35 Pain Score was compared between all participants of pembro combo arm and control arm as a pre-specified secondary analysis. Also per protocol, TTD in EORTC QLQ-H&N35 Pain Score was compared separately between all participants of pembro mono arm and control arm and is presented later in the record. (NCT02358031)
Timeframe: Baseline up to approximately 12 months

Pembro Mono vs Control: Change From Baseline to Week 15 in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score

"The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the GHS question How would you rate your overall health during the past week? (Item 29) and the QoL question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 15 in the GHS/QoL combined score was compared between all participants of the pembro mono arm and the control arm as a pre-specified secondary analysis. As specified by the protocol, change from baseline to Week 15 in the GHS/QoL combined score was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record." (NCT02358031)
Timeframe: Baseline, Week 15

Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in All Participants

ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR for all participants in the pembro mono arm and control arm. Per protocol, ORR was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1

ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR for all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro mono arm and control arm. Per protocol, ORR was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20

ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR for all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro mono arm and control arm. Per protocol, ORR was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

Pembro Mono vs Control: OS in All Participants

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro mono arm and control arm. Per protocol, OS was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

Pembro Mono vs Control: OS in Participants With PD-L1 CPS ≥1

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥1. Per protocol, OS was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

Pembro Mono vs Control: OS in Participants With PD-L1 CPS ≥20

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥20. Per protocol, OS was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among All Participants

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here out of all participants in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record." (NCT02358031)
Timeframe: Month 12

Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record." (NCT02358031)
Timeframe: Month 12

Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record." (NCT02358031)
Timeframe: Month 12

Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among All Participants

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here out of all participants in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record." (NCT02358031)
Timeframe: Month 6

Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record." (NCT02358031)
Timeframe: Month 6

Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record." (NCT02358031)
Timeframe: Month 6

Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in All Participants

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for all participants in the pembro mono arm and control arm. Per protocol, PFS was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record." (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥1. Per protocol, PFS was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record." (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥20. Per protocol, PFS was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record." (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

Pembro Mono vs Control: TTD in the EORTC QLQ- H&N35 Pain Score

EORTC QLQ-H&N35 is a 35-item questionnaire developed to assess QoL of head and neck cancer participants and consists of 7 multi-item scales that assess pain, swallowing, senses, speech, social eating, social contact and sexuality. Participant responses to the Pain scale (Items 31-34) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. TTD in EORTC QLQ-H&N35 Pain Score defined as the time from baseline to the first onset of a ≥10 point decrease from baseline, with confirmation. Per protocol, TTD in EORTC QLQ-H&N35 Pain Score was compared between all participants of pembro mono arm and control arm as a pre-specified secondary analysis. Also per protocol, TTD in EORTC QLQ-H&N35 Pain Score was compared separately between all participants of pembro combo arm and control arm and is presented earlier in the record. (NCT02358031)
Timeframe: Baseline up to approximately 12 months

Pembro Mono vs Control: TTD in the EORTC QLQ- H&N35 Swallowing Score

EORTC QLQ-H&N35 is a 35-item questionnaire developed to assess QoL of head and neck cancer participants and consists of 7 multi-item scales that assess pain, swallowing, senses, speech, social eating, social contact and sexuality. Participant responses to the Swallowing scale (Items 35-38) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. TTD in EORTC QLQ-H&N35 Swallowing Score defined as the time from baseline to the first onset of a ≥10 point decrease from baseline, with confirmation. Per protocol, TTD in EORTC QLQ-H&N35 Swallowing Score was compared between all participants of pembro mono arm and control arm as a pre-specified secondary analysis. Also per protocol, TTD in EORTC QLQ-H&N35 Swallowing Score was compared separately between all participants of pembro combo arm and control arm and is presented earlier in the record. (NCT02358031)
Timeframe: Baseline up to approximately 12 months

Pembro Mono vs Control: TTD in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score

"EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to the GHS question How would you rate your overall health during the past week? (Item 29) and the QoL question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. TTD in GHS/QoL defined as the time from baseline to the first onset of a ≥10 point decrease from baseline in GHS/QoL combined score, with confirmation. Per protocol, TTD in GHS/QoL combined score was compared between all participants of pembro mono arm and control arm as a pre-specified secondary analysis. Also per protocol, TTD in GHS/QoL combined score was compared separately between all participants of pembro combo arm and control arm and is presented earlier in the record." (NCT02358031)
Timeframe: Baseline up to approximately 12 months

Best Overall Response Rate (ORR)

The Best ORR was based on imaging and classified according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria. The BOR rate was defined as the number of participants whose BOR was either complete response (CR) or partial response (PR), relative to the number of participants belonging to the trial set of interest. CR was defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. (NCT02383966)
Timeframe: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)

Disease Control Rate (DCR)

The DCR was based on imaging and classified according to RECIST Version 1.1 criteria. The DCR was defined as the number of participants whose Best Overall Response is either CR, PR or stable disease (SD), divided by the number of participants belonging to the trial set of interest multiplied by 100. CR was defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on trial. (NCT02383966)
Timeframe: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)

Duration of Response (DOR)

DOR was determined for participants whose BOR was either CR or PR. It was defined as the time from the first assessment of CR or PR until the event defining PFS time. PFS time was defined as the time in months from the date of randomization until first observation of PD (based on imaging as assessed by IRC), or death due to any cause when death occurs within 60 days after the last tumor assessment or randomization (whichever is later). CR was defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. (NCT02383966)
Timeframe: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)

Overall Survival (OS) Time

The OS time was defined as the time from randomization to the date of death. If a participant was alive at the time of analysis, survival time was censored at the last date when the participant was known to be alive. If this date was after data cut-off, participants were censored at the date of data cut-off. OS was measured using Kaplan-Meier (KM) estimates. (NCT02383966)
Timeframe: Time from date of randomization up to data cutoff (assessed up to 904 days)

Progression-free Survival (PFS) Time, as Assessed by an Independent Review Committee (IRC)

PFS time was defined as the time in months from the date of randomization until first observation of PD (based on imaging as assessed by IRC), or death due to any cause when death occurs within 60 days after the last tumor assessment or randomization (whichever is later). PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on trial; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 millimeter. PFS was measured using Kaplan-Meier (KM) estimates. (NCT02383966)
Timeframe: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)

Progression-free Survival (PFS) Time, as Assessed by the Investigator

PFS time was defined as the time in months from the date of randomization until first observation of PD (radiologically confirmed by Investigator), or death due to any cause when death occurs within 60 days after the last tumor assessment or randomization (whichever is later). PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on trial; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 millimeter. PFS was measured using Kaplan-Meier (KM) estimates. (NCT02383966)
Timeframe: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Treatment Emergent Adverse Events Leading to Death and AEs Leading to Discontinuation

An Adverse event (AE) was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state up to 30 days after last administration. TEAEs included both Serious TEAEs and non-serious TEAEs. (NCT02383966)
Timeframe: Time from date of randomization up to data cutoff (assessed up to 904 days)

Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)

"The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question How would you rate your overall health during the past week? (Item 29) and the Quality of Life (QoL) question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was reported by treatment arm as a pre-specified secondary analysis for all participants who were PD-L1 CPS ≥10." (NCT03189719)
Timeframe: Baseline, Week 18

Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score in Participants With ESCC

"The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question How would you rate your overall health during the past week? (Item 29) and the Quality of Life (QoL) question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was reported by treatment arm as a pre-specified secondary analysis for all participants who had ESCC." (NCT03189719)
Timeframe: Baseline, Week 18

Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)

"The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question How would you rate your overall health during the past week? (Item 29) and the Quality of Life (QoL) question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was reported by treatment arm as a pre-specified secondary analysis for all participants who had ESCC and who were PD-L1 CPS ≥10." (NCT03189719)
Timeframe: Baseline, Week 18

Change From Baseline To Week 18 in the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) Combined Score in All Participants

"The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question How would you rate your overall health during the past week? (Item 29) and the Quality of Life (QoL) question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was reported by treatment arm as a pre-specified secondary analysis for all participants." (NCT03189719)
Timeframe: Baseline, Week 18

DOR Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by the investigator, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death due to any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, DOR is reported here for all participants of the ITT population (all randomized) who had CR or PR, and were PD-L1 CPS ≥10. (NCT03189719)
Timeframe: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)

DOR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by the investigator, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death due to any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, DOR is reported here for all participants of the ITT population (all randomized) who had CR or PR, and who had ESCC. (NCT03189719)
Timeframe: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)

DOR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by the investigator, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death due to any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, DOR is reported here for all participants of the ITT population (all randomized) who had CR or PR, and who had ESCC and were PD-L1 CPS ≥10. (NCT03189719)
Timeframe: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)

Duration of Response (DOR) Per RECIST 1.1 As Assessed By Investigator in All Participants

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by the investigator, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death due to any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, DOR is reported here for all participants of the ITT population (all randomized) who had CR or PR. (NCT03189719)
Timeframe: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)

Number of Participants Discontinuing Study Treatment Due to an AE

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants that discontinued any study drug due to an AE was reported for each treatment arm. (NCT03189719)
Timeframe: Up to approximately 27 months

Number of Participants With an Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants that experienced at least one AE was reported for each treatment arm. (NCT03189719)
Timeframe: Up to approximately 28 months

Objective Response Rate (ORR) Per RECIST 1.1 As Assessed By Investigator in All Participants

ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by the investigator. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for all participants of the ITT population (all randomized). (NCT03189719)
Timeframe: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)

ORR Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)

ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by the investigator. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for all participants of the ITT population (all randomized) who were PD-L1 CPS ≥10. (NCT03189719)
Timeframe: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)

ORR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC

ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by the investigator. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for all participants of the ITT population (all randomized) who had ESCC. (NCT03189719)
Timeframe: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)

ORR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)

ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by the investigator. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for all participants of the ITT population (all randomized) who had ESCC and who were PD-L1 CPS ≥10. (NCT03189719)
Timeframe: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)

OS in All Participants

Overall survival was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS is reported here for all participants of the ITT population (all randomized). (NCT03189719)
Timeframe: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)

OS in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)

Overall survival was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS is reported here for all participants of the ITT population (all randomized) who were PD-L1 CPS ≥10. (NCT03189719)
Timeframe: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)

OS in Participants With ESCC

Overall survival was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS is reported here for all participants of the ITT population (all randomized) who had ESCC. (NCT03189719)
Timeframe: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)

Overall Survival (OS) in Participants With Esophageal Squamous Cell Carcinoma (ESCC) Whose Tumors Are Programmed Cell Death-Ligand 1 (PD-L1) Biomarker-Positive (Combined Positive Score [CPS] ≥10)

Overall survival was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS is reported here for all participants of the Intent-To-Treat (ITT) population (all randomized) who had ESCC and who were PD-L1 CPS ≥10. (NCT03189719)
Timeframe: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)

PFS Per RECIST 1.1 As Assessed By Investigator in All Participants

PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 as assessed by the investigator, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, PFS is reported here for all participants of the ITT population (all randomized) who were PD-L1 CPS ≥10. (NCT03189719)
Timeframe: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)

PFS Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)

PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 as assessed by the investigator, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, PFS is reported here for all participants of the ITT population (all randomized) who were PD-L1 CPS ≥10. (NCT03189719)
Timeframe: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)

Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) As Assessed By Investigator in Participants With ESCC

PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 as assessed by the investigator, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, PFS is reported here for all participants of the ITT population (all randomized) who had ESCC. (NCT03189719)
Timeframe: Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)

Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)

"The EORTC QLQ-OES18 is a disease-specific questionnaire developed and validated to address measurements specific to esophageal cancer and contains 18 items assessing symptoms of dysphagia, pain, reflux symptoms, eating restrictions, anxiety, dry mouth, taste, body image, and hair loss. For the purposes of this study, the Dysphagia subscale (three items), Pain subscale (three items), and Reflux subscale (two items) were evaluated. All subscale items were scored using a four-point Likert scale with the following response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Raw scores for the subscales were standardized into a range of 0 to 100 by linear transformation, with higher symptom scores representing a higher (worse) level of symptoms. Change from baseline to Week 18 in the Dysphagia, Pain, and Reflux subscales was reported for participants who were PD-L1 CPS≥10 in each treatment arm. Negative changes from baseline indicate a decrease in symptom severity." (NCT03189719)
Timeframe: Baseline, Week 18

Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC

"The EORTC QLQ-OES18 is a disease-specific questionnaire developed and validated to address measurements specific to esophageal cancer and contains 18 items assessing symptoms of dysphagia, pain, reflux symptoms, eating restrictions, anxiety, dry mouth, taste, body image, and hair loss. For the purposes of this study, the Dysphagia subscale (three items), Pain subscale (three items), and Reflux subscale (two items) were evaluated. All subscale items were scored using a four-point Likert scale with the following response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Raw scores for the subscales were standardized into a range of 0 to 100 by linear transformation, with higher symptom scores representing a higher (worse) level of symptoms. Change from baseline to Week 18 in the Dysphagia, Pain, and Reflux subscales was reported for participants with ESCC in each treatment arm. Negative changes from baseline indicate a decrease in symptom severity." (NCT03189719)
Timeframe: Baseline, Week 18

Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)

"The EORTC QLQ-OES18 is a disease-specific questionnaire developed and validated to address measurements specific to esophageal cancer and contains 18 items assessing symptoms of dysphagia, pain, reflux symptoms, eating restrictions, anxiety, dry mouth, taste, body image, and hair loss. For the purposes of this study, the Dysphagia subscale (three items), Pain subscale (three items), and Reflux subscale (two items) were evaluated. All subscale items were scored using a four-point Likert scale with the following response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Raw scores for the subscales were standardized into a range of 0 to 100 by linear transformation, with higher symptom scores representing a higher (worse) level of symptoms. Change from baseline to Week 18 in the Dysphagia, Pain, and Reflux subscales was reported for participants with ESCC who were PD-L1 CPS≥10 in each treatment arm. Negative changes from baseline indicate a decrease in symptom severity." (NCT03189719)
Timeframe: Baseline, Week 18

Change From Baseline in the EORTC Quality Of Life Questionnaire Oesophageal Module (QLQ-OES18) Subscale Scores in All Participants

"The EORTC QLQ-OES18 is a disease-specific questionnaire developed and validated to address measurements specific to esophageal cancer and contains 18 items assessing symptoms of dysphagia, pain, reflux symptoms, eating restrictions, anxiety, dry mouth, taste, body image, and hair loss. For the purposes of this study, the Dysphagia subscale (three items), Pain subscale (three items), and Reflux subscale (two items) were evaluated. All subscale items were scored using a four-point Likert scale with the following response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Raw scores for the subscales were standardized into a range of 0 to 100 by linear transformation, with higher symptom scores represent a higher (worse) level of symptoms. Per protocol, change from baseline to Week 18 in the Dysphagia, Pain, and Reflux subscales was reported for all participants in each treatment arm. Negative changes from baseline indicate a decrease in symptom severity." (NCT03189719)
Timeframe: Baseline, Week 18

Number of Patients Who Had Response by RECIST Criteria (Response Evaluation Criteria in Solid Tumors)

Complete remission (complete disappearance of disease), partial remission [more than 30% decrease in tumor measurement by RECIST (Response evaluation criteria in solid tumors)]. (NCT00400205)
Timeframe: every 3 months

Tumor Change by Baseline Acetylated Tubulin Expression Score

"Percent change in TNM stage of tumors after three cycles of study treatment was assessed to see if baseline acetylated tubulin (AT) expression predicts treatment success. Decreasing tumor stage change (a negative number) indicates that the tumor is responding to treatment while an increase means that the severity of the tumor is not decreasing. Immunohistochemistry (IHC) analysis of AT expression was performed in formalin-fixed, paraffin-embedded, pre-treatment tissues. The staining was scored based upon intensity according to the following criteria: 0=no staining, 1+=weak tumor staining, 2+=moderate tumor staining, 3+=moderate to high tumor staining, and 4+=high tumor staining.~Data presented are adopted from Saba, NF, et. al. Acetylated Tubulin (AT) as a Prognostic Marker in Squamous Cell Carcinoma of the Head and Neck. Head and Neck Pathology (2014) 8:66-72." (NCT00400205)
Timeframe: Baseline, After 3 cycles of study treatment

Best Overall Response (BOR) Rate

The BOR rate is defined as the percentage of the participants having achieved confirmed complete response (CR) or partial response (PR) as the best overall response according to radiological assessments (based on RECIST Version 1.0). (NCT00705016)
Timeframe: Evaluations will be performed every 6 weeks until progression reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011)

Disease Control Rate

The disease control rate is defined as the percentage of participants having achieved confirmed CR, PR or stable disease (SD) as best overall response according to radiological assessments (based on RECIST Version 1.0). (NCT00705016)
Timeframe: Evaluations will be performed every 6 weeks until progression reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011)

Duration of Response

Duration of response is defined as the time from the first assessment of CR or PR until the date of the first occurrence of progressive disease (PD), or until the date of death. (NCT00705016)
Timeframe: Time from first assessment of CR or PR until PD, death or last tumor assessment, reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011)

Overall Survival (OS) Time

The OS time is defined as the time from randomization to death. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whichever is earlier. (NCT00705016)
Timeframe: Time from randomization to death, reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011)

Progression-free Survival (PFS) Time: Investigator Read

The PFS is defined as the duration from randomization until radiological progression (based on response evaluation criteria in solid tumors [RECIST] Version 1.0) or death due to any cause. Only deaths within 84 days of last tumor assessment are considered. Participants without event are censored on the date of last tumor assessment. Investigator read is the assessment of all imaging by the treating physician at the local trial site. (NCT00705016)
Timeframe: Time from randomization to disease progression, death or last tumor assessment, reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011)

Safety - Number of Participants Experiencing Any Adverse Event

Please refer to Adverse Events section for details of individual serious adverse events and other adverse events (NCT00705016)
Timeframe: Time from first assessment of CR or PR until PD, death or last tumor assessment, reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011)

Time to Treatment Failure (TTF)

TTF is defined as the time from randomization to date of the first occurrence of; progression, discontinuation of treatment due to progression or adverse event, start of new anticancer therapy, withdrawal of consent, or death (within 84 days of last tumor assessment). Participants without event are censored on the date of last tumor assessment. (NCT00705016)
Timeframe: Time from randomization to disease progression, death or last tumor assessment, reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011)

Area Under the Concentration Curve (AUC) of Cetuximab at Steady State

A total of 4 samples were collected during combination therapy, from the first dose of 250 mg/m^2 cetuximab in Cycle 1 (Day 1) through the final dose in Cycle 3 (Week 3) and used to report AUC of cetuximab at steady state during Part 2 of the study. As specified in the protocol, PK samples were not collected during Part 1 of the study, Safety Lead-In, or during Part 2 monotherapy. (NCT01081041)
Timeframe: Part 2: Weekly from Cycle 1, Day 1 through Cycle 3, Week 3: 0 h (immediately postdose), 24 h, 96 h, and 168 h postdose

Cmax of Cetuximab at Steady State

A total of 4 samples were collected at various times during combination therapy, from the third dose of 250 mg/m^2 cetuximab in Cycle 1 (Week 3) through the final dose in Cycle 3 (Week 3) and used to report Cmax of cetuximab at steady state during Part 2 of the study. As specified in the protocol, PK samples were not collected during Part 1 of the study, Safety Lead-In, or during Part 2 monotherapy. (NCT01081041)
Timeframe: Part 2: Weekly from Cycle 1, Week 3 through Cycle 3, Week 3: 0 h (immediately postdose), 24 h, 96 h, and 168 h postdose

Maximum Serum Concentration (Cmax) of Cetuximab Following 400 mg/m² Cetuximab Dosing

The Cmax of cetuximab following 400 mg/m² cetuximab dosing during Part 2 of the study is reported. As specified in the protocol, pharmacokinetics (PK) samples were not collected during Part 1 of the study, Safety Lead-In or during Part 2 monotherapy. (NCT01081041)
Timeframe: Part 2: Cycle 1, Day 1: 0 hours [(h); immediately postdose], 1 h, 2 h, and 24 h postdose

Number of Participants Who Had TEAEs; Data Analysis Cut-Off: January 23, 2013

January 23, 2013 is the date when the first participant in the BI-manufactured cetuximab treatment arm switched to US commercial cetuximab due to changes in the manufacturing process for the BI-manufactured cetuximab necessitating the need to switch participants to US commercial cetuximab. Each participant who switched treatments received at least 2 cycles of BI-manufactured cetuximab before switching. All other components of their treatment regimen remained unchanged. The number of participants who had TEAEs during combination therapy is reported. Using January 23 cut-off, data is un-confounded by lack of BI-manufactured cetuximab. TEAEs were defined as serious and other non-serious adverse events (AEs) that occurred or worsened after study treatment (regardless of causality). TEAE information for Safety Lead-in group available in Reported Adverse Event module which is summary of serious and other non-serious AEs regardless of causality. (NCT01081041)
Timeframe: Part 2: Baseline to end of combination therapy or date first participant switched to US commercial cetuximab (up to 18 weeks)

Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs); Data Analysis Cut-Off: September 27, 2013

September 27, 2013 is the date when data was last collected for the primary endpoint. Prior to this date, the manufacturing process for the BI-manufactured cetuximab was changed necessitating the need to switch participants to US commercial cetuximab. All other components of their treatment regimen remained unchanged and participants stayed in their original reporting group. Therefore, the number of participants in the BI-manufactured cetuximab treatment arm who had TEAEs includes TEAEs while participants received BI-manufactured and US-commercial cetuximab. Using September 27 cut-off, the analysis of TEAEs is confounded by the switch from BI-manufactured to US commercial cetuximab. TEAEs were defined as serious and other non-serious AEs that occurred or worsened after study treatment (regardless of causality). TEAE information for Safety Lead-In group available in Reported Adverse Events module which is summary of serious and other non-serious AEs regardless of causality. (NCT01081041)
Timeframe: Part 2: Baseline to end of combination therapy (up to 18 weeks)

Number of Participants With Anti-Cetuximab Antibodies

(NCT01081041)
Timeframe: Day 1, Week 1 of Cycles 3 and 5 (postbaseline samples were collected prior to infusion).

Overall Survival (OS)

OS was defined as duration from the date of randomization to the date of death from any cause. For each participant not known to have died as of the 23 October 2014 data cutoff date for the analysis, OS was censored at the date last known to be alive. In addition, any participants on Arm B who was switched from BI-manufactured cetuximab to ImClone-manufactured cetuximab was censored at the time of the switch. (NCT01081041)
Timeframe: Parts 1 and 2: Randomization to Date of Death from any Cause (Up to 36.3 Months)

Percentage of Participants Having a Best Response of CR, PR, or Stable Disease (SD) - Disease Control Rate (DCR)

Response was defined using RECIST, v1.0 criteria. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. Progressive Disease (PD) was defined as having at least a 20% increase in the sum of the longest diameter of target lesions. Stable Disease (SD) was defined as small changes that did not meet the above criteria. (NCT01081041)
Timeframe: Parts 1 and 2: Randomization to Progression of Disease (Up to 32.7 Months)

Percentage of Participants Having a Confirmed Best Response of Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])

Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version [v]1.0) criteria. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. Percentage of participants with a confirmed CR or PR=(number of participants whose best overall response was CR or PR)/(number of participants treated)*100. (NCT01081041)
Timeframe: Parts 1 and 2: Randomization to Progression of Disease (Up to 32.7 Months)

Progression-Free Survival (PFS)

PFS was defined as duration from the date of randomization to the first date of objective progressive disease (PD) or death from any cause. For each participant who was not known to have died or to have had objective PD as of the 23 October 2014 data cutoff date for the analysis, PFS was censored at the date of the participant's last complete tumor assessment prior to that cutoff date. In addition, any participant in Arm B who was switched from BI-manufactured cetuximab to ImClone-manufactured cetuximab was censored at the time of the switch. (NCT01081041)
Timeframe: Parts 1 and 2: Randomization to Progression of Disease or Death from any Cause (Up to 32.7 Months)

Reviews

15 reviews available for fluorouracil and Carcinoma, Squamous Cell of Head and Neck

Trials

49 trials available for fluorouracil and Carcinoma, Squamous Cell of Head and Neck