osimertinib and Drug-Related-Side-Effects-and-Adverse-Reactions

In the AURA3 trial, individuals received osimertinib 80 mg once daily or chemotherapy for advanced non-small cell lung cancer. Here, we explore patient-reported symptoms possibly related to treatment.. AURA3 was an open-label, randomized phase III trial involving 419 patients. As part of the trial's exploratory objectives, individuals were asked to complete the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) electronically, first weekly for 18 weeks and then every 3 weeks for up to 57 weeks, subject to the availability of validated local-language versions (English, German, Japanese and Spanish versions were available).. In total, 161 patients (38%; 102 receiving osimertinib, 59 receiving chemotherapy) provided data for PRO-CTCAE analyses (mean age: 64 years; 63% women). Diarrhea was reported more commonly with osimertinib than with chemotherapy, and was mostly graded as occurring rarely or occasionally. Decreased appetite was reported less commonly with osimertinib than with chemotherapy. The proportion of patients reporting nausea changed little from baseline with osimertinib and increased with chemotherapy. Few patients reported vomiting. Both nausea and vomiting were generally graded as mild in severity. Fatigue was reported less commonly with osimertinib than with chemotherapy, and was mostly graded as mild or moderate. Of patients reporting fatigue, the proportion grading it as interfering at least 'somewhat' with their usual or daily activities was lower with osimertinib than with chemotherapy.. Symptoms were generally mild and not frequent, with some differences in symptom patterns between the two treatment groups. The results support and complement the AURA3 trial data and give insight into patients' experience with treatment.

Topics: Acrylamides; Aged; Aniline Compounds; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Drug-Related Side Effects and Adverse Reactions; Fatigue; Female; Humans; Lung Neoplasms; Male; Middle Aged; Nausea; Neoplasm Staging; Patient Reported Outcome Measures; Piperazines; Vomiting

On November 13, 2015, the FDA granted accelerated approval to osimertinib (TAGRISSO; AstraZeneca), a breakthrough therapy-designated drug for the treatment of patients with metastatic EGFR T790M mutation-positive non-small cell lung cancer, as detected by an FDA-approved test, with progression on or after EGFR tyrosine kinase inhibitor therapy. Approval was based on durable tumor response rates in two single-arm, multicenter trials: the dose extension cohort of a first-in-human trial (FIH; AURA extension;

Topics: Acrylamides; Adult; Aged; Aged, 80 and over; Aniline Compounds; Carcinoma, Non-Small-Cell Lung; Dose-Response Relationship, Drug; Drug Approval; Drug-Related Side Effects and Adverse Reactions; ErbB Receptors; Female; Humans; Male; Middle Aged; Mutation; Neoplasm Metastasis; Piperazines; Protein Kinase Inhibitors

Topics: Acrylamides; Aniline Compounds; Drug-Related Side Effects and Adverse Reactions; Humans; Indoles; Pigmentation Disorders; Purpura; Pyrimidines

Osimertinib was a third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), which approved by the US Food and Drug Administration (FDA) in 2015 for treatment of non-small cell lung cancer (NSCLC). Our study was to explore the adverse events (AEs) caused by osimertinib through data mining of the US FDA Adverse Event Reporting System (FAERS), and provide reference for clinical safety. Data of osimertinib were collected from the FAERS database covering the period from first quarter of 2016 to the fourth quarter of 2021. Disproportionality analyses was employed to quantify the associated AE signals of osimertinib and detect the risk signals from the data in the FAERS database. Reporting odds ratio (ROR) was used to detect the risk signals from the data in the FAERS database. The definition relied on system organ class (SOCs) and preferred terms (PTs) by the Medical Dictionary for Regulatory Activities (MedDRA). Totally, 9,704,33 reports were collected from the FAERS database, 10,804 reports of osimertinib were identified as the 'primary suspected (PS)' AEs. Osimertinib induced AEs occurred in 27 organ systems. 68 significant disproportionality PTs satisfying with the four algorithms were retained at the same time. Unexpected significant AEs such as scrotal volvulus, hepatic function abnormal, venous thromboembolisms might also occur. The median onset time of osimertinib-associated AEs was 58 days (interquartile range [IQR] 14-212 days), and the majority of the AEs occurred within the first 30 days after osimertinib initiation. Our study found significant new AEs signals of osimertinib and might provide support for clinical monitoring and risk identification of osimertinib.

Topics: Adverse Drug Reaction Reporting Systems; Carcinoma, Non-Small-Cell Lung; Drug-Related Side Effects and Adverse Reactions; ErbB Receptors; Humans; Lung Neoplasms; Pharmacovigilance; United States; United States Food and Drug Administration

Topics: Acrylamides; Adolescent; Adult; Aged, 80 and over; Aniline Compounds; Antineoplastic Agents; Drug-Related Side Effects and Adverse Reactions; Female; Glucocorticoids; Humans; Immune Checkpoint Inhibitors; Ipilimumab; Male; Middle Aged; Neoplasms; Nivolumab; Retrospective Studies; Uveitis, Anterior; Vemurafenib

We sought to describe corneal epithelial changes after using epidermal (EGFR) or fibroblast growth factor receptor (FGFR) inhibitors as chemotherapy and to clarify incidence and prognosis.. Retrospective chart review.. Among 6871 patients and 17 EGFR or FGFR inhibitors, 1161 patients (16.9%) referred for ophthalmologic examination. In total, 1145 patients had disease-related or unrelated ocular complications. Among 16 patients with treatment-related ocular complications, three patients had treatment-related radiation retinopathy and one patient showed treatment-related corneal ulcer. Finally the authors identified that, in 12 patients, three EGFR inhibitors and two FGFR inhibitors caused corneal epithelial lesions. Vandetanib, Osimertinib, and ABT-414 caused vortex keratopathy in nine patients, while ASP-5878 and FPA-144 caused epithelial changes resembling corneal dysmaturation in three patients. The mean interval until symptoms appeared was 246 days with vandetanib, 196 days with osimertinib, 30 days with ABT-414, 55 days with ASP-5878, and 70 days with FPA-144. The mean of the lowest logarithm of minimal angle of resolution visual acuity results of the right and left eyes after chemotherapy were 0.338 and 0.413. The incidence rates of epithelial changes were 15.79% with vandetanib, 0.5% with osimertinib, 100% with ABT-414, 50.0% with ASP-5878, and 18.2% with FPA-144. After excluding deceased patients and those who were lost to follow-up or still undergoing treatment, we confirmed the reversibility of corneal lesions after the discontinuation of each agent. Seven patients showed full recovery of their vision and corneal epithelium, while three achieved a partial level of recovery. Although patients diagnosed with glioblastoma used prophylactic topical steroids before and during ABT-414 therapy, all developed vortex keratopathy.. EGFR and FGFR inhibitors are chemotherapy agents that could make corneal epithelial changes. Contrary to the low probability of ocular complication with old EGFR drugs, recently introduced EGFR and FGFR agents showed a high incidence of ocular complication with severe vision distortion. Doctors should forewarn patients planning chemotherapy with these agents that decreased visual acuity could develop due to corneal epithelial changes and also reassure them that the condition could be improved after the end of treatment without the use of steroid eye drops.. This study was approved by the institutional review board (IRB) of Samsung Medical Center (IRB no. 2019-04-027) and was conducted according to the principles expressed in the Declaration of Helsinki.

Topics: Acrylamides; Adult; Aniline Compounds; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Corneal Diseases; Drug-Related Side Effects and Adverse Reactions; Epithelium, Corneal; ErbB Receptors; Female; Humans; Immunoconjugates; Male; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Quinazolines; Receptors, Fibroblast Growth Factor; Retrospective Studies; Therapies, Investigational; Vision Disorders; Visual Acuity

Adverse event reports submitted to the US Food and Drug Administration (FDA) were analyzed to map the safety profile of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). We conducted a disproportionality analysis of the adverse events (AEs) of EGFR-TKIs (gefitinib, erlotinib, afatinib, osimertinib) by data mining using the FDA adverse event reporting system (AERS) database, and by calculating the reporting odds ratios (ROR) with 95% confidence intervals. The FDA AERS database contained 27,123 EGFR-TKI-associated AERs within the reporting period from January 1, 2004 to March 31, 2018. Thirty-three preferred terms (PTs) were selected for analysis, and significant RORs were most commonly observed in the skin, nail, gastrointestinal tract, hepatic, eyes, and lungs. Unexpected adverse drug reactions were found in the "intestinal obstruction" and "hypokalaemia" in gefitinib and erlotinib, "hyponatraemia" in gefitinib, erlotinib and afatinib, "alopecia"in erlotinib, "hair growth abnormal" in afatinib, but not in "nausea" and "vomiting" listed on drug labels. The results of this study are consistent with clinical observation, suggesting the usefulness of pharmacovigilance research should be corroborated with the real-world FAERS data.

Topics: Acrylamides; Adverse Drug Reaction Reporting Systems; Afatinib; Aniline Compounds; Data Mining; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; ErbB Receptors; Erlotinib Hydrochloride; Gefitinib; Humans; Pharmacovigilance; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Safety; United States; United States Food and Drug Administration

Topics: Acrylamides; Aniline Compounds; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Line; Cell Line, Tumor; Cell Proliferation; Drug Design; Drug Resistance, Neoplasm; Drug-Related Side Effects and Adverse Reactions; ErbB Receptors; Humans; Inhibitory Concentration 50; Lung Neoplasms; Mutation; Structure-Activity Relationship

Topics: Acrylamides; Aniline Compounds; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Drug-Related Side Effects and Adverse Reactions; ErbB Receptors; Exanthema; Female; Humans; Lung Neoplasms; Middle Aged; Mutation; Stevens-Johnson Syndrome; Tears; Ulcer