Introduction: Immune-checkpoint inhibitor (ICI) efficacy in patients with NSCLC harboring molecular alterations remains poorly elucidated. This study was undertaken to determine ICI efficacy against BRAF-, HER2-, MET-, and RET-NSCLC in a real-world setting.Methods: In this retrospective, multicenter study in ICItreated BRAF-, HER2-, MET-or RET-NSCLCs, we analyzed clinical characteristics and outcomes: ICI-treatment duration, progression-free survival (PFS), objective response rate, duration of response, and overall survival (OS).Results: There were 107 patients with NSCLC (mean age, 65.5 y) included from 21 centers: 37% were neversmokers, 54% were men, and 93% had adenocarcinoma. Among them, 44 had BRAF mutation (V600: 26), 23 had HER2 mutation, 30 had MET mutation, and nine had RET translocation. Programmed cell death ligand 1 (PD-L1) status was known for 70 patients and was greater than or equal to 1% in 34 patients. Before ICI, patients had received a median of one treatment line. Median duration of response, PFS, and OS were 15.4 (95% confidence interval [CI]: 12.6-not reached [NR]) months, 4.7 (95% CI: 2.3-7.4) months, and 16.2 (95% CI: 12.0-24.0) months, respectively, for the entire cohort. The response rates for BRAF-V600, BRAF-non-V600, HER2, MET, and RET-altered NSCLC were 26%, 35%, 27%, 36%, and 38%, respectively. For patients who were PD-L1 negative and those who were PD-L1 positive, PFS was 3.0 (95% CI: 1.2-NR) and 4.3 (95% CI: 2.1-8.5) months, respectively, and OS was 11.7 (95% CI: 4.1-NR) and 35.8 (95% CI: 9.0-35.2) months, respectively. Toxicities were reported in 28 patients (26%), including 11 patients (10%) with a grade greater than or equal to three. Conclusions:In this real-world setting, ICI efficacy against patients with BRAF-, HER2-, MET-, or RET-NSCLC seemed close to that observed in unselected patients with NSCLC. Large prospective studies on these subsets of patients are needed.

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Background and Aims:The impact of diagnosis and treatment delays for non-small cell lung cancer management is poorly understood, even if the literature on the subject is currently increasing in importance. We have few indicators that can serve as reference for quality assurance actions. The objective of this review was to review the literature on the subject. Methods: A literature search, using the words 'human lung cancer delay' and 'human lung cancer waiting time' , was undertaken in Medline database. Results: Several studies analyzed these delays mostly in a monocentric setting. There is an important variability in the definition of these delays, in the collection methods and in the results obtained. However, it seems distinctly clear that long delays are frequently observed in less symptomatic patients and, therefore, are accompanied by better prognosis.

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NCT02293733.

ObjectiveTo assess efficacy and tolerance of EGFR tyrosine-kinase inhibitors (TKIs) for advanced EGFR-mutated non-small cell lung cancer (NSCLC) in octogenarians.Patients and methodsPatients aged 80 years or older with EGFR-mutated NSCLC treated by EGFR TKI between January 2011 and March 2015 whatever the line of treatment were retrospectively selected.Results20 centers retrospectively included 114 patients (women, 77.2%; Caucasians, 98.3%; mean age, 83.9 years). A performance status of 0–1 or 2–3 at diagnosis was reported for 71.6% and 28.4% of patients, respectively. Overall, 95.6% of patients had adenocarcinomas and histological stage at diagnosis was stage IV for 79.8% of patients. EGFR mutations were identified mainly on exon 19 (46.5%) and exon 21 (40.4%). A geriatric assessment was performed in 35.1% of patients. TKI treatment was administered to 97.3% of patients as first or second line of treatment. Overall response rate and disease control rate were 63.3% (69/109) and 78.9% (86/109), respectively. Median progression-free survival was 11.9 months (95% confidence interval [CI], 8.6–14.7) and median overall survival was 20.9 months (95% CI, 14.3–27.1). After progression, 36/95 (37.9%) patients received a new line of chemotherapy. Main toxicities were cutaneous for 66.7% of patients (grade 3–4, 10%), diarrhea for 56.0% (grade 3–4, 15%; grade 5, 2%) and others for 25.7% (grade 3–4, 41%).ConclusionsOctogenarians with EGFR-mutated NSCLC treated by EGFR TKI had clinical outcomes and toxicity profile comparable to younger patients. Geriatric assessment appeared to be underused in this population.

Background Mutations in BRAF are rare oncogene mutations, found in 2% of non-small-cell lung cancers (nsclcs). Little information is available about the management of patients with BRAF-mutated nsclc, except for those included in clinical trials. We undertook the present study to assess the clinical characteristics, management, and outcomes of those patients in a real-life setting.MethodsThis retrospective multicentre observational study included all patients with BRAF-mutated nsclc diagnosed between January 2012 and December 2014.ResultsPatients (n = 59) from 24 centres were included: 57.6% men; mean age: 64.5 ± 14.5 years; 82% with a performance status of 0–1 at diagnosis; smoking status: 40.3% current, 32.6% former; 93% with adenocarcinoma histology; 75% stage iv; 78% with V600E mutations; 2 with EGFR and 2 with ALK co-mutations. Of the stage iv patients, 79% received first-line therapy (14.2% anti-BRAF), and 48% received second-line treatment (23.8% anti-BRAF). Response rate and progression-free survival were, respectively, 51.7% and 8.7 months [95% confidence interval (ci): 6.4 months to 15.2 months] for first-line therapy and 35.3% and 4.1 months (95% ci: 2 months to 10.9 months) for second-line treatments. The 2-year overall survival was 58.5% (95% ci: 45.8% to 74.8%). Outcomes in patients with stage iv nsclc harbouring BRAF V600E mutations (n = 32) did not differ significantly from those of patients with other BRAF mutations.ConclusionsIn this real-world analysis, most nsclc patients with a BRAF mutation were men and current or former smokers. Survival appears to be better in these BRAF-mutated patients than in nsclc patients without an oncogenic driver.

BackgroundMutation of human receptor tyrosine kinase epidermal growth factor receptor-2 (HER2) is a rare event, found in approximately 1% non-small cell lung cancers (NSCLC). The objective was to investigate the clinical characteristics and management of HER2-mutated NSCLCs in a real-life setting.MethodsThis multicenter study described NSCLCs harboring HER2 mutations diagnosed between January 2012 and December 2014, according their clinical characteristics, management, and outcomes: response rate (RR), progression-free survival (PFS), and overall survival (OS).ResultsThirty patients were included: 66.7% women; median age 65.2 ± 12 years; never or former smokers 73.3%. Of the stage IV patients (n = 23), 86% received first-line platin doublet chemotherapy: RR 61.5% and PFS 6.7 (95% CI 5.9–9.5) months; 52.1% received a second-line therapy: RR 18.2% and PFS 4.9 (95% CI 2.5–11.9) months. Median OS of stage IV was 10.7 months and 2-year OS was 27.2% (95% CI 11.7–63.2). All patients with stage I–III NSCLCs were alive at 2 years.ConclusionThe rarity of HER2-mutated NSCLCs requires specific studies.