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Background: Capmatinib is a selective MET inhibitor with demonstrated efficacy in a phase II study of non-small cell lung cancer (NSCLC) patients harboring METex14 mutations. However, the real-world outcomes of capmatinib are largely unknown. From June 2019, the French Early Access Program (EAP) provided capmatinib to METex14 NSCLC patients who were ineligible for or for whom first-line standard therapies had failed., Methods: IFCT-2104 CAPMATU was a multicenter study that included all METex14 NSCLC patients who received capmatinib as part of the EAP until August 2021. The primary endpoints were time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS) and objective response rate (ORR)., Results: A total of 146 patients were included. The median age was 74.9 years, 56.6 % were never-smokers, and 32.4 % had brain metastases. The median TTF, median PFS and median OS from capmatinib initiation were 5.1 months (95 % CI 4.2-6.0), 4.8 months (95 % CI 4.0-6.0) and 10.4 months (95 % CI 8.3-13.2), respectively. Evaluation of the best response to capmatinib was available for 134 patients and resulted in an ORR of 55.3 % (95 % CI 46.8 %-63.6 %). The median PFS was 7.7 months for treatment-naïve patients and 6.0 and 4.1 months for patients who had received one or 2 + prior lines of treatment, respectively. For patients with brain metastases, the median PFS was 3.0 months. Capmatinib had a known and manageable safety profile, with grade 3 to 4 adverse events, mostly peripheral edema (8.2 %), occurring in 17.8 % of patients., Conclusion: In this large real-world study of METex14 NSCLC patients, the efficacy of capmatinib was confirmed, with a manageable safety profile, even in patients with brain metastases and in those who received several lines of treatment. This study reinforces the key role of capmatinib for these patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M. Ferreira: Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, BMS. A. Swalduz: Financial Interests, Personal, Other, honoraria: AstraZeneca, Janssen, Roche, Amgen, BMS; Financial Interests, Personal, Advisory Role: AstraZeneca, Janssen, Roche, Amgen, BMS, Pfizer, Lilly. P. du Rusquec: Financial Interests, Personal, Other, Travel, Accommodations: Roche, Pfizer, Sandoz, Daiichi Sankyo, Merck, Novartis, Lilly, Amgen, Eisai, BMS, Takeda, AstraZeneca, Janssen, Sanofi. Advisory Role: Sanofi, Takeda. A.C. Toffart: Financial Interests, Personal, Advisory Role: AstraZeneca, MSD, BMS, Roche, Amgen, Takeda, Jannsen. J. Raimbourg: Financial Interests, Personal, Other, Travel, Accommodations, Expenses: BMS. V. Gounant: Financial Interests, Personal, Advisory Role: BMS, AstraZeneca, Takeda; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Sanofi, Pfizer. S. Couraud: Financial Interests, Personal, Other, honoraria: Amgen, AstraZeneca, BMS, MSD, Roche, Sanofi, Fabentech, Boehringer Ingelheim, Takeda; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, BMS, MSD, Roche, Sanofi, Chugai, Novartis, Pfizer, Sysmex, Cellgene, Takeda, Janssen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, Roche, Takeda. M. Wislez: Financial Interests, Personal, Advisory Role: AstraZeneca, MSD, Amgen, BMS, Roche; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, MSD, Amgen, BMS, Roche; Financial Interests, Institutional, Funding, research funding: AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, MSD, Amgen, BMS, Roche. C. Descarpentries reports personal fees and nonfinancial support from AstraZeneca, personal fees and nonfinancial support from Novartis Pharma SAS, nonfinancial support from Roche SAS, nonfinancial support from Boehringer Ingelheim france, nonfinancial support from Pfizer, outside the submitted work; G. Herbreteau reports personal fees and nonfinancial support from Pierre Fabre Oncology. V. Westeel: Financial Interests, Personal, Other, Honoraria: AstraZeneca, BMS, Amgen, Roche; Financial Interests, Personal, Advisory Role: MSD, Takeda; Financial Interests, Personal, Speaker’s Bureau: BMS, AstraZeneca, Roche, MSD, Pfizer, Amgen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: BMS, AstraZeneca, Sanofi. A. B. Cortot: Financial Interests, Personal, Other, Consulting fees: Roche Novartis; Financial Interests, Personal, Other, Honoraria: Novartis Pfizer Takeda Roche; Financial Interests, Personal, Advisory Board: Roche Novartis Pfizer Takeda. All other authors have declared no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Pembrolizumab 400 mg every six weeks (Q6W) and nivolumab 480 mg every four weeks (Q4W) are used since 2020 and the coronavirus disease 2019 (COVID-19) pandemic. This recommendation relied on pharmacokinetic and pharmacodynamic models. The objective of the IDEE (Immunothérapie Double dose Etendue: Experience bretonne) study is to determine the safety and efficacy of this treatment regimen in real life conditions., Methods: We conducted an observational, retrospective, multicentric study including 117 patients with advanced non-small cell lung cancer (NSCLC) who received pembrolizumab Q6W or nivolumab Q4W between March 2020 and March 2021., Results: The median age was 67 years, 68% were men with predominantly lung adenocarcinoma. The median time to double-dose regimen failure (TDDF) was 9.2 months. The survival rate at 12 months was 79%. TDDF was not influenced by sex, line of treatment, pathologic subtypes or anti-programmed cell death protein 1 (PD-1) antibody. There was no correlation between TDDF and duration of prior exposition to immunotherapy before switching. Sixty-eight patients experienced double-dose treatment failure, 28% because of toxicity including five definitive discontinuations. Five grade ≥3 immune-adverse events were reported included two cases of pneumonitis, all responding to corticosteroid therapy., Conclusions: Our multicentric cohort supports the feasibility of pembrolizumab Q6W and nivolumab Q4W for patients with advanced NSCLC. There is no warning signal regarding safety neither efficacy in our real-life data., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-141/coif). H.L. receives honoraria, participation on Advisory Board and support for meeting travel from Roche, MSD, Bristol Myers Squibb, Astrazeneca, Sanofi. G.D.C. reports participation on a Data Safety Monitoring Board or Advisory Board for MSD, BMS, Roche, Astrazeneca, Takeda and Sanofi and support for attending meetings by Pfizer. C.R. reports consulting fees from Astrazeneca, MSD, Takeda and BMS. The other authors have no conflicts of interest to declare., (2024 Translational Lung Cancer Research. All rights reserved.)

Background: Management of stage-III-N2 non-small-cell lung cancer (NSCLC) based on a multimodal strategy (surgery or radiotherapycombined with systemic drugs) remains controversial. Patients are treated with a curative intent, and available data suggestprolonged survival after complete resection. However, no consensual definition of "tumor resectability" exists. This study aimed to analyze the concordanceamong French tumor board meeting (TBM)-emittedtherapeutic decisions forstage-III-N2 NSCLC., Methods: Six patients with stage-III-N2 NSCLC discussed at Saint-Etienne University Hospital'sthoracic TBMs were selected, anonymouslyreported, and submitted to the participating TBMs. The primary goal of this multicenter, prospective, observational study was to assess the consistency of TBMpanel decisions for each case. The secondary endpointwas identifying the demographic or technical factors that potentiallyaffected decision-making., Results: Twenty-seven TBMs from university hospitals, a cancer center, general hospitals, and a private hospitalparticipated in this study. None of their decisions for the six cases were unanimous.The decisions were homogenous for three cases (78%, 85%, and 88% TBMs opted for medical treatment, respectively),andmore ambivalent for the other three (medical versus surgical strategies were favored by 44%/56%, 46%/54%, and 58%/42% TBMs, respectively). Interestingly, decisions regarding chemoradiationand perioperative chemotherapyinthe medical and surgical strategies, respectively, were also discordant. Hospital type, specialist participation in TBMs, and activity volumes were not significantly associated with therapeutic decisions., Conclusion: The results of this study highlight substantial disparities amongFrench TBMs regarding therapeutic management of stage-III-N2 NSCLC. The decisions were not associated with local conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Few epidemiological data are available on surgically treated Caucasian patients with non-small-cell lung cancers (NSCLCs) harboring epidermal growth factor receptor ( EGFR ) mutations. The main objective of this study was to describe, in the real-world setting, these patients' incidence, clinical, and tumoral characteristics., Methods: The participating centers included all consecutive localized non-squamous NSCLC patients undergoing surgery between January 2018 and December 2019 in France. EGFR status was determined retrospectively when not available before surgery., Results: The study includes 1391 no squamous NSCLC patients from 16 centers; EGFR status was determined before surgery in 692 (49.7%) of the cases and conducted as part of the study for 699 (50.3%); 171 (12.3%) were EGFR mutated; median age: 70 (range: 36-88) years; female: 59.6%; never smokers: 75.7%; non-squamous histology 97.7%, programmed death ligand-1 expression 0%/1-49%/⩾50 in 60.5%/25.7%/13.8%, respectively. Surgery was predominantly lobectomy (81%) or segmentectomy (14.9%), with systematic lymph node dissection in 95.9%. Resection completeness was R0 for 97%. Post-surgery staging was as follows: IA: 52%, IB: 16%, IIA: 4%, IIB: 10%, IIIA: 16%, and IIIB: 0.05%; EGFR mutation exon was Del19/exon 21 ( L858R )/20/18 in 37.4%/36.8%/14%, and 6.4% of cases, respectively; 31 (18%) patients received adjuvant treatment (chemotherapy: 93%, EGFR tyrosine kinase inhibitor: 0%, radiotherapy: 20%). After a median follow-up of 31 (95% confidence interval: 29.6-33.1) months, 45 (26%) patients relapsed: 11/45 (24%) locally and 34 (76%) with metastatic progression. Median disease-free survival (DFS) and overall survival were not reached and 3-year DFS was 60%., Conclusion: This real-world analysis provides the incidence and outcomes of resected EGFR -mutated NSCLCs in a European patient cohort., Competing Interests: J-BA: In the last 5 years, J-BA has received honoraria for attending scientific meetings, speaking, organizing research, or consulting, from Boehringer Ingelheim, Hoffman-Roche, Takeda, BMS, MSD, Astra Zeneca, Amgen, and Pfizer., (© The Author(s), 2024.)

Objectives: Few data are available on the impact of KRAS mutation in patients with advanced non-squamous non-small cell lung cancer (aNSCLC) treated with immunotherapy. This analysis assessed the impact of KRAS mutation on the efficiency of first-line pembrolizumab immunotherapy in aNSCLC patients with PD-L1 ≥ 50 %., Methods: This was a secondary analysis of the ESCKEYP study, a retrospective, national, multicenter study which included consecutively all metastatic NSCLC patients who initiated first-line treatment with pembrolizumab monotherapy from May 2017 (date of pembrolizumab availability in this indication in France) to November 22, 2019 (pembrolizumab-chemotherapy combination approval). Progression-free survival (PFS) and overall survival (OS) were calculated from the start of pembrolizumab treatment by the Kaplan-Meier method. Tumor response and PFS were assessed locally., Results: Among the 681 non-squamous aNSCLC PD-L1 ≥ 50 % patients treated with pembrolizumab in the first line, 227 (33.0 %) had a KRAS mutation (KRAS G12C, 12.5 %; KRAS non-G12C, 20.5 %). Except among non-smokers (KRAS G12C, 0 %; KRAS non-G12C, 2.9 %; no KRAS mutation, 9.2 %), patients presented no differences in terms of sex, age, number and sites of metastatic disease at diagnosis, use of corticosteroids, use of antibiotics, and for biological factors between wild-type KRAS, KRAS G12C and non-KRAS G12C groups. Median (95 % CI) PFS in months were 7.0 (3.7-14) for KRAS G12C, 4.8 (3.4-6.7) for KRAS non-G12C and 8.5 (7.3-10.6) for wild-type KRAS genotypes (p = 0.23). Median OS were 18.4 (12.6-NR), 20.6 (11.4-NR) and 27.1 (18.7-34.2) months, respectively (p = 0.57)., Conclusion: No difference in efficacy was observed in non-squamous aNSCLC patients treated with first-line pembrolizumab immunotherapy whether they presented a KRAS G12C, non KRAS G12C or wild-type KRAS genotype., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Programmed death receptor 1 (PD1) checkpoint inhibitors are known for immune mediated toxicities such as colitis, endocrinopathies and pneumonitis. However, other rare adverse effects are reported in the literature. Nivolumab is an anti-PD1 immunotherapy used in the second line of non-small cell lung cancer (NSCLC). We report two cases of rare toxicities occurring under nivolumab in patients without a history of dysimmunity. A 79-year-old patient with a large-cell carcinoma showed a muscle weakness after the second course, revealing myositis with a CPK grade IV elevation as well as symptoms of myasthenia. The diagnosis of myositis was confirmed by a muscle biopsy. An 82-year-old patient followed for bronchial adenocarcinoma with EGFR mutation, presented with nivolumab shoulder and hip pain with extreme fatigue. After further investigations, the diagnosis of systemic erythematosus lupus was retained. Investigations led to the diagnosis of systemic lupus erythematosus. For both patients treatment was interrupted and systemic corticosteroid therapy was initiated permitting resolution of symptoms. The occurrence of symptoms of dysimmunity should attract the attention of the clinician, leading to discontinuation of anti-PD1 therapy and corticosteroid therapy. Retreatment after symptoms resolution must be collegially discussed if no alternative therapeutic is available., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Erlotinib maintenance treatment improves progression-free survival compared with observation after first-line chemotherapy in unselected advanced non-small cell lung cancer (NSCLC). Very few cardiac adverse effects have been observed in phase III studies on tyrosine kinase inhibitors (TKI). We report the case of a 71-year-old woman with metastatic NSCLC treated with cisplatin/pemetrexed and then erlotinib maintenance therapy. After 26 months of TKI therapy, she developed dilated cardiomyopathy. Despite symptomatic treatment, left ventricular ejection fraction decreased to 25%. Ischemic heart disease was excluded by coronary angiography and cardiac magnetic resonance imaging, and no other cause was found. Erlotinib was stopped, and cardiac resynchronization therapy by pacemaker was initiated. This case report highlights the possible cardiotoxic effects of long-term erlotinib and suggests the need for close clinical and echocardiographic follow-up of patients receiving long-term TKI therapy., (© 2016 S. Karger AG, Basel.)