Immune-Checkpoint Inhibitors for Malignant Pleural Mesothelioma: A French, Multicenter, Retrospective Real-World Study.

Backgrounds: Malignant pleural mesothelioma (MPM) is a cancer with poor prognosis. Second-line and onward therapy has many options, including immune-checkpoint inhibitors with demonstrated efficacy: 10−25% objective response rate (ORR) and 40−70% disease-control rate (DCR) in clinical trials on selected patients. This study evaluated real-life 2L+ nivolumab efficacy in MPM patients and looked for factors predictive of response. Methods: This retrospective study included (September 2017−July 2021) all MPM patients managed in 11 French centers. Results: The 109 enrolled patients' characteristics were: median age: 69 years; 67.9% men; 82.6% epithelioid subtype. Strictly, second-line nivolumab was given to 51.4%. Median PFS and OS were 3.8 (3.2−5.9) and 12.8 (9.2−16.4) months. ORR was 17/109 (15.6%); 34/109 patients had a stabilized disease (DCR 46.8%). Univariable analysis identified several parameters as significantly (p < 0.05) prognostic of OS [HR (95% CI)]: biphasic subtype: 3.3 (1.52−7.0), intermediate Lung Immune Prognostic Index score: 0.46 (0.22−0.99), progression on the line preceding nivolumab: 2.1 (1.11−3.9) and age > 70 years: 2.5 (1.5−4.0). Multivariable analyses retained only biphasic subtype: 3.57 (1.08−11.8) and albumin < 25 g/L: 10.28 (1.5−70.7) as significant and independent predictors. Conclusions: Second-line and onward nivolumab is effective against MPM in real life but with less effectiveness in >70 years. Ancillary studies are needed to identify the predictive factors.

Non-Small Cell Lung Cancer Patients Harboring HER2 Mutations: Clinical Characteristics and Management in a Real-Life Setting. Cohort HER2 EXPLORE GFPC 02-14.

BACKGROUND: Mutation 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. METHODS: This 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). RESULTS: Thirty 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. CONCLUSION: The rarity of HER2-mutated NSCLCs requires specific studies.

Real-Life Efficacy of Osimertinib in Pretreated Octogenarian Patients with T790M-Mutated Advanced Non-small Cell Lung Cancer.

BACKGROUND: The resistance mutation T790M is reported in 50-60% of patients pretreated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Osimertinib has been approved in these patients, but data in octogenarians remain rare. OBJECTIVE: The objective of this retrospective analysis was to evaluate in real life the efficacy of osimertinib in a population of octogenarian patients. METHODS: This retrospective multicentric study included pretreated octogenarian patients with EGFR T790M-mutated advanced non-small cell lung cancer (NSCLC) in the setting of the French early access program for osimertinib. The primary endpoints were progression-free survival (PFS) and overall survival (OS) from osimertinib initiation. RESULTS: In total, 43 patients were included (mean age 84.6 years; women 90.7%: adenocarcinoma 100%; never smokers 90.5%; at osimertinib initiation: performance status ≥ 2, 42.4%; stage 4, 93.0%; brain metastases 16.3%). Patients received a median of two lines of treatment before osimertinib initiation, and all received first- or second-generation EGFR TKIs before osimertinib (first line in 79.1%). Osimertinib was used as a second-line treatment in 41.9% of cases and third line or more in 58.1%. Median PFS was 17.5 (95% confidence interval [CI] 12.2-19.0) months for the entire population: 20.6 (95% CI 18.8-not reached) months in patients with brain metastases and 16.7 (95% CI 10.4-18.9) months in patients without (p = 0.1). There was no significant difference for osimertinib treatment as second or third line or more (17.1 vs. 18.6 months, respectively). OS was 22.8 (95% CI 15.7-not reached) months from osimertinib initiation. CONCLUSION: The efficacy of osimertinib as second-line treatment or more in octogenarian pretreated patients with EGFR T790M-mutated advanced NSCLC in a real-life setting was similar to that in randomized controlled trials.

Prediagnosis weight loss, a stronger factor than BMI, to predict survival in patients with lung cancer.

OBJECTIVES: Recent studies have demonstrated that elevated BMI is associated with improved survival in patients with lung cancer. According to the authors, this "obesity paradox" could be a true benefit or a spurious relationship. In this context, data from the French KBP-2010-CPHG cohort (7,051 patients followed up for primary lung cancer diagnosed in 2010 in the respiratory medicine departments of 104 nonacademic hospitals) were analyzed. METHODS: Patients were stratified according to BMI at diagnosis using the definition of the French-Speaking Society of Clinical Nutrition and Metabolism (Société Francophone de Nutrition Clinique et Métabolisme). Survival was analyzed using log-rank and a univariate Cox model. Prognostic factors were identified using a multivariate Cox model with backward elimination procedure, and with or without inclusion of prediagnosis weight loss in the model. RESULTS: Patients were followed for a median 20.2 months. At diagnosis, respectively 12%, 28%, 45%, and 15% of the 6,595 patients with BMI data were obese, overweight, normal-weight, and underweight; 35%, 43%, 57%, and 75% reported prediagnosis weight loss (i.e., weight loss within the 3 months prior to diagnosis). One-year survival (% [95% CI]) was 53% [50%-57%], 50%, [48%-52%], 43%, [42%-45%], and 32% [29%-35%] in obese, overweight, normal-weight, and underweight patients, respectively (p < 0.001). It was particularly low in underweight patients with prediagnosis weight loss: 27% [24-30%]. BMI did not remain an independent prognostic factor associated with survival when prediagnosis weight loss was introduced in the Cox model. Risk of death was increased by 17%, 23%, and 46% in patients with <5 kg, 5-10 kg, or ≥10 kg prediagnosis weight loss, respectively (p < 0.001). CONCLUSION: BMI is an easy but crude assessment tool. Other variables should be used to improve management of patients, and understanding of how prediagnosis body size and nutritional status are associated with cancer survival.