osimertinib and Pneumonia

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the primary treatment in treating with EGFR mutant nonsmall cell lung cancer (NSCLC). This systematic review and meta-analysis aimed to evaluate the efficacy and safety of the third-generation EGFR-TKI, osimertinib, and summarize the risk factors associating with outcome after osimertinib treatment.. The Ovid Medline, Embase, Cochrane Library, and Pubmed were systematically searched due to December 10, 2019. All the studies that mentioned the overall survival (OS), progression-free survival (PFS), treatment response, and adverse events (AEs) of osimertinib were involved in our study. Hazard ratio (HR) with 95% confidence intervals was used for comparing OS and PFS.. A total of 47 studies were included in the systematic review, of which 14 studies were used to compare the efficacy between osimertinib and other EGFR-TKI or chemotherapy. Patients treating with osimertinib favors a higher OS and PFS in all the patients (HR = 0.56 and 0.38, P < .001, respectively), and in subgroup analysis, compared with other treatments. Median 55% T790 mutant NSCLC patients might experience partial response, and 25% of patients remained as stable disease. The incidence of severe AE ranged from 0% to 5%, and the most common severe AE was pneumonia (3%). Patients with the T858R mutation may have a better OS than Del 19 mutation (HR = 0.55, P = .037), while patients who have a smoking history may have a higher risk of progression than never-smoker patients (HR = 1.47, P = .028).. Osimertinib has an impressive antitumor activity compared with prior EGFR-TKI and chemotherapy with an acceptable response and tolerable AEs. EGFR mutation type and smoking status were the risk factors for mortality and progression in NSCLC patients.

Topics: Acrylamides; Aniline Compounds; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cigarette Smoking; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Pneumonia; Progression-Free Survival; Survival Rate

Although osimertinib is a standard first-line treatment for patients with advanced-stage non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations, the incidence rate of pneumonitis associated with osimertinib is high. However, there are few reports about the safety and efficacy of osimertinib rechallenge after the development of pneumonitis.. We conducted a retrospective multicentre cohort study of consecutive patients who developed pneumonitis associated with osimertinib as a first-line and received osimertinib rechallenge. The primary outcome was the incidence rate of any grade pneumonitis after osimertinib rechallenge. The secondary outcome was treatment efficacy in patients after osimertinib rechallenge.. In total, 33 patients who received osimertinib rechallenge were included. Of them, 26 patients had grade 1, 6 patients had grade 2, and 1 patient had grade 3 initial pneumonitis. The median follow-up period after the osimertinib rechallenge was 16.9 months (interquartile range, 11.1-21.3 months). After the start of osimertinib rechallenge, five patients (15%) experienced mild relapsed pneumonitis. Three of the five patients had similar imaging patterns for initial and relapsed pneumonitis. No significant differences in characteristics were observed between patients with and without relapsed pneumonitis. The median progression-free survival after osimertinib rechallenge was not achieved (95% confidence interval: 10.3 months - not reached).. Osimertinib rechallenge was feasible and effective for patients who developed initial pneumonitis associated with first-line osimertinib therapy. Osimertinib might be considered a treatment option even after the development of mild initial pneumonitis.

Topics: Aniline Compounds; Carcinoma, Non-Small-Cell Lung; Cohort Studies; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Pneumonia; Protein Kinase Inhibitors; Retrospective Studies

Osimertinib has demonstrated impressive efficacy as a first-line treatment for patients with advanced epidermal growth factor receptor (EGFR) mutation-positive (m+) lung cancer. Drug-related pneumonitis (DRP) is a potentially lethal complication of osimertinib treatment, but reliable real-world data currently are lacking.. What is the prevalence of osimertinib-induced DRP in first-line settings? What are the characteristics, clinical impact, and risk factors of osimertinib-induced DRP?. We conducted a retrospective multicenter cohort study of patients who received osimertinib as a first-line treatment for advanced EGFR m+ non-small cell lung cancer (NSCLC) between August 2018 and December 2019. All chest CT scans and clinical information during osimertinib exposure were collected until June 2020. The primary end point was DRP incidence identified through central review.. A total of 452 patients from 18 institutions were evaluated. Eighty patients (18%) had a diagnosis of DRP (all grades), and 21 patients (4.6%) had a diagnosis of grade 3 or more DRP. Among the patients with DRP, 46% were identified as having transient asymptomatic pulmonary opacity (TAPO). Regarding the CT scan patterns, organizing pneumonia, simple pulmonary eosinophilia, hypersensitivity pneumonia, diffuse alveolar damage, and nonspecific interstitial pneumonia were found in 30, 21, 18, 9, and two patients (38%, 26%, 23%, 11%, and 3%), respectively. In multivariate analysis, smoking history was identified as an independent risk factor for DRP (hazard ratio, 1.72; 95% CI, 1.01-2.89; P = .046). In the 3-month landmark analysis, DRP was associated with poor treatment efficacy; however, the presence of TAPO did not affect treatment efficacy negatively.. For osimertinib treatment in first-line settings, the frequency of DRP was considerably elevated to 18 %, and half of these patients exhibited TAPO features.

Topics: Carcinoma, Non-Small-Cell Lung; Cohort Studies; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Pneumonia; Protein Kinase Inhibitors

Osimertinib-induced pneumonitis usually manifests as ground glass opacities (GGO) on chest computed tomography (CT) scans. Here, we encountered a case involving a 42-year-old woman who had nodule-type pneumonitis mimicking lung abscess or tumor recurrence caused by osimertinib. When a nodular pattern is seen on the chest CT scan of a patient receiving osimertinib treatment, drug-induced pneumonitis should be considered as a differential diagnosis. To the best of our knowledge, this is the first case of osimertinib-induced pneumonitis that manifested as a nodule-type pneumonitis mimicking lung abscess or tumor recurrence on chest CT scan.

Topics: Adult; Female; Humans; Lung Abscess; Neoplasm Recurrence, Local; Pneumonia; Tomography, X-Ray Computed

Topics: Acrylamides; Aniline Compounds; Humans; Lung Neoplasms; Mutation; Pneumonia; Protein Kinase Inhibitors

Osimertinib is the standard therapy for epidermal-growth-factor-receptor (EGFR)-mutant lung cancers. We herein report a case of osimertinib-induced interstitial lung disease (OsiILD) with an organizing pneumonia (OP) pattern and provide a literature-based review. Six months after osimertinib administration, a 75-year-old woman with right pleural carcinomatosis developed ILD with an OP pattern. After salvage chemotherapy, osimertinib with corticosteroid was successfully re-administered. A literature review suggested that 1) OsiILD with an OP pattern was rare but should be recognized, and 2) re-administration of osimertinib in OsiILD was successful in select patients. A criterion that determines whether a patient would benefit from re-administration is warranted.

Topics: Acrylamides; Adenocarcinoma; Aged; Aniline Compounds; Antineoplastic Agents; ErbB Receptors; Female; Humans; Lung Diseases, Interstitial; Lung Neoplasms; Pneumonia; Protein Kinase Inhibitors; Salvage Therapy

Epithelial growth factor receptor (EGFR) directed tyrosine kinase inhibitor (TKI) treatment is the standard approach in patients with advanced, EGFR-mutated non-small cell lung cancer (NSCLC). Although benefit/risk ratio is favorable for these TKI and side effects are manageable in the vast majority of patients, severe and even life-threatening side effects have been reported. TKI-induced interstitial lung disease (ILD) has been reported for single cases in modest severity, predominantly in EGFR-TKI pretreated patients. Here, we report a case of successful stabilization of a life-threatening ILD in a de novo T790M mutated NSCLC during first-line treatment with osimertinib. As osimertinib will be used more often in many EGFR-positive NSCLC patients in the future, this potentially life-threatening side effect should receive special attention, especially in first-line treatment.

Topics: Acrylamides; Aged; Aniline Compounds; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Pneumonia; Protein Kinase Inhibitors; Treatment Outcome

Drug-induced pneumonitis is rare, and can result in death. Here, we present a report of a patient with adenocarcinoma harboring EGFR exon 19 deletion mutation treated with osimertinib as first-line treatment. After six days of treatment, extremely early onset severe pneumonitis was diagnosed. Discontinuation of osimertinib as well as administration of corticosteroid, and retreatment with osimertinib were successful. This case report highlights that extremely early onset severe pneumonitis can occur after osimertinib administration, and retreatment of osimertinib may be a useful treatment option after resolution of pneumonitis.

Topics: Acrylamides; Adenocarcinoma of Lung; Aniline Compounds; Female; Humans; Lung Neoplasms; Middle Aged; Pneumonia

Concurrent programmed death-ligand-1 (PD-(L)1) plus osimertinib is associated with severe immune related adverse events (irAE) in epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). Now that PD-(L)1 inhibitors are routinely used as adjuvant and first-line treatments, sequential PD-(L)1 inhibition followed by osimertinib use may become more frequent and have unforeseen serious toxicity.. We identified patients with EGFR-mutant NSCLC who were treated with PD-(L)1 blockade and EGFR- tyrosine kinase inhibitors (TKIs), irrespective of drug or sequence of administration (total n = 126). Patient records were reviewed to identify severe (NCI-CTCAE v5.0 grades 3-4) toxicity.. Fifteen percent [6 of 41, 95% confidence interval (CI) 7% to 29%] of all patients treated with sequential PD-(L)1 blockade followed later by osimertinib developed a severe irAE. Severe irAEs were most common among those who began osimertinib within 3 months of prior PD-(L)1 blockade (5 of 21, 24%, 95% CI 10% to 45%), as compared with >3-12 months (1 of 8, 13%, 95% CI 0% to 50%), >12 months (0 of 12, 0%, 95% CI 0% to 28%). By contrast, no severe irAEs were identified among patients treated with osimertinib followed by PD-(L)1 (0 of 29, 95% CI 0% to 14%) or PD-(L)1 followed by other EGFR-TKIs (afatinib or erlotinib, 0 of 27, 95% CI 0% to 15%). IrAEs occurred at a median onset of 20 days after osimertinib (range 14-167 days). All patients with irAEs required steroids and most required hospitalization.. PD-(L)1 blockade followed by osimertinib is associated with severe irAE and is most frequent among patients who recently received PD-(L)1 blockade. No irAEs were observed when osimertinib preceded PD-(L)1 blockade or when PD-(L)1 was followed by other EGFR-TKIs. This association appears to be specific to osimertinib, as no severe irAEs occurred with administration of other EGFR-TKIs.

Topics: Acrylamides; Adult; Aged; Aged, 80 and over; Aniline Compounds; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; ErbB Receptors; Female; Humans; Lung Neoplasms; Male; Middle Aged; Nivolumab; Pneumonia; Protein Kinase Inhibitors; Retrospective Studies; Young Adult

Topics: Acrylamides; Aged; Aged, 80 and over; Aniline Compounds; Brain Neoplasms; Carcinoma, Adenosquamous; Disease Progression; ErbB Receptors; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Mutation; Piperazines; Pneumonia; Protein Kinase Inhibitors; Steroids