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Simple Summary: Immune-checkpoint inhibitors have only been studied in clinical trials for second-line and now first-line malignant pleural mesothelioma. Sometimes, results found in clinical trials do not translate to real-life settings. We aim to study second-line and onward nivolumab in malignant pleural mesothelioma to verify its effectiveness in France. We enrolled 109 patients from 11 centers in France. Our study proves in multivariate analysis that nivolumab has an efficacy against MPM. An intermediate LIPI score seems predictive of good response, but less in those < 70 years and for the first time in biphasic subtype. Ancillary studies are needed to more deeply explore these findings. 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. [ABSTRACT FROM AUTHOR]

Highlights • Efficacy of osimertinib in real-world setting and in clinical trials was comparable. • Osimertinib was efficient in patients with brain metastasis. • Osimertinib was efficient in second or more lines in T790 M EGFR-mutated patients. • EGFR exon 19 deletion had a better susceptibility to osimertinib. Abstract Objectives The efficacy of osimertinib in pretreated patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR T790 M resistance mutation was demonstrated in clinical trials. However, data on efficacy of osimertinib in real world remain rare. Materials and methods This retrospective multicentric study analyzed T790M-positive advanced NSCLC patients enrolled in French early access program for osimertinib. Patients were pretreated with first- or second-generation EGFR tyrosine-kinase inhibitor and for a majority with chemotherapy. Primary endpoints were progression-free survival (PFS) and overall survival (OS) from osimertinib initiation. Results 205 patients (mean age, 69.5 years; female, 68.8%; adenocarcinoma, 97.5%, never-smokers, 71.5%) were analyzed. Osimertinib was used in second and third line in 18.0% and 82.0% of patients, respectively. Median PFS was 12.4 (95% CI, 10.1–15.1) months. In patients with and without cerebral metastasis, PFS was 9.7 (7.7–13.5) and 15.1 (12.0–17.1) months (p = 0.21), respectively. PFS in second and third line or more was 12.6 (6.7–17.5) and 12.4 (9.7–15.3) months, respectively. Median PFS in patients with EGFR exon 19 deletion and exon 21 mutation was 13.5 (10.1–16.0) and 9.7 (7.4–13.2) months, respectively (p = 0.049). Median OS since osimertinib initiation was 20.5 (16.9–24.3) months: 23.1 (18.6–27.8) and 18.0 (12.2–22.2) months in patients without and with cerebral metastasis (p = 0.11); 17.5 (11.6–27.8) and 21.7 (17.3–24.3) months as second or third line of treatment or more (p = 0.46), respectively. Median OS in patients with EGFR exon 19 deletion and exon 21 mutation was 23.1 (18.6–25.7) and 15.3 (11.6–21.7) months, respectively (p = 0.03). Osimertinib dosage was modified in 8.0% of patients and definitively discontinued for adverse events in 5.9%. Fifty patients benefited from rebiopsy (persistence of T790 M mutation, 44.7%; C797S mutation, 21.1%; cMET amplification, 8.0%). Conclusion In pretreated patients with T790M-mutated advanced NSCLC, the efficacy of osimertinib appears similar in real-world setting to that of clinical trials. [ABSTRACT FROM AUTHOR]

Objective: To provide a nationwide description of postoperative outcomes and analysis of prognostic factors following adrenalectomy for metastases., Background: Adrenal glands are a common site of metastases in many malignancies. Diagnosis of adrenal metastases is on the rise, leading to an increasing number of patient candidates for surgery without consensual management., Methods: We conducted a population-based study between January 2012 and December 2022 using the French National Health Data System (SNDS) and the Eurocrine registry (NCT03410394). The first database exhaustively covers all procedures carried out in France, while the second provides more clinical information on procedures and tumor characteristics, based on the experience of 11 specialized centers., Results: From the SNDS, we extracted 2515 patients who underwent adrenalectomy for secondary malignancy and 307 from the Eurocrine database. The most common primary malignancies were lung cancer (n=1203, 47.8%) and renal cancer (n=555, 22.1%). One-year survival was 84.3% (n=2120). Thirty-day mortality and morbidity rates were, respectively, 1.3% (n=32) and 29.9% (n=753, including planned intensive care unit - stays). Radiotherapy within the year before adrenalectomy was significantly associated with higher 30-day major complication rates ( P =0.039). In the Eurocrine database, the proportion of laparoscopic procedures reached 85.3% without impairing resection completeness (R0: 92.9%). Factors associated with poor overall survival were the presence of extra-adrenal metastases (hazard ratio =0.64; P =0.031) and incomplete resection (≥R1; hazard ratio=0.41; P =0.015)., Conclusions: The number of patients who can receive local treatment for adrenal metastases is rising, and adrenalectomy is more often minimally invasive and has a low morbidity rate. Subsequent research should evaluate which patients would benefit from adrenal surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The management of stage III non-small-cell lung cancer (NSCLC) remains heterogeneous and complex, even after the approval of immune checkpoint inhibitors post-chemoradiotherapy (CRT). This observational study from France evaluated real-world practices in managing stage III NSCLC., Methods: Between 2020 and 2022, we conducted a physician practice survey in 41 medical centers across France, and retrospectively analyzed aggregated information from 417 consecutive charts of patients with stage III NSCLC. We collected information on diagnostic and staging procedures, biomarker testing, surgical and non-surgical treatments, and follow-up., Results: According to the physician survey, diagnostic workup of stage III NSCLC primarily relied on positron emission tomography/computed tomography and brain magnetic resonance imaging, performed for the majority of patients in 100 % and 78 % of centers, respectively. Of 417 patient charts, 414 were evaluable with 53 % of patients having stage IIIA disease, 37 % IIIB, and 10 % IIIC. The most common node involvement was N2 (59 %). Programmed death-ligand 1 testing was conducted for 98 % of patients. Invasive staging (mediastinoscopy or endobronchial ultrasound) was performed in 41 % of patients, of whom 83 % had N2 or N3 nodal involvement. Surgical resection was offered to 120 patients (29 %), with 85 % achieving R0 resection. In 292 charts of patients with unresectable stage III NSCLC, 190 patients (65 %) were offered CRT followed by consolidation immunotherapy. Within these patients, concurrent CRT was more frequently employed (52 %) than sequential CRT (13 %)., Conclusions: Diagnostic procedures and treatment modalities in French medical centers generally align with clinical guidelines for stage III NSCLC, except for invasive staging that was less commonly performed than expected., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jean-Bernard Auliac reports financial support was provided by AstraZeneca. Jean-Bernard Auliac reports a relationship with AstraZeneca that includes: consulting or advisory, paid expert testimony, speaking and lecture fees, and travel reimbursement. Jean-Bernard Auliac reports a relationship with Takeda Pharmaceutical Company Limited that includes: consulting or advisory and paid expert testimony. Jean-Bernard Auliac reports a relationship with Bristol Myers Squibb Co that includes: consulting or advisory, paid expert testimony, and travel reimbursement. Jean-Bernard Auliac reports a relationship with Janssen Pharmaceuticals Inc that includes: consulting or advisory, paid expert testimony, and speaking and lecture fees. Jean-Bernard Auliac reports a relationship with Amgen Inc that includes: consulting or advisory, paid expert testimony, and speaking and lecture fees. Jean-Bernard Auliac reports a relationship with MSD France SAS that includes: speaking and lecture fees and travel reimbursement. Jean-Bernard Auliac reports a relationship with Sanofi that includes: paid expert testimony, speaking and lecture fees, and travel reimbursement. Jean-Bernard Auliac reports a relationship with Boehringer Ingelheim GmbH that includes: travel reimbursement. Laurent Greillier reports a relationship with Bristol Myers Squibb Co that includes: funding grants and speaking and lecture fees. Laurent Greillier reports a relationship with MSD France SAS that includes: funding grants, speaking and lecture fees, and travel reimbursement. Laurent Greillier reports a relationship with Takeda Pharmaceutical Company Limited that includes: funding grants, speaking and lecture fees, and travel reimbursement. Laurent Greillier reports a relationship with Pfizer that includes: funding grants, speaking and lecture fees, and travel reimbursement. Laurent Greillier reports a relationship with Roche that includes: funding grants and speaking and lecture fees. Laurent Greillier reports a relationship with Amgen Inc that includes: funding grants and speaking and lecture fees. Laurent Greillier reports a relationship with Sanofi that includes: funding grants and speaking and lecture fees. Laurent Greillier reports a relationship with Janssen Pharmaceuticals Inc that includes: funding grants and speaking and lecture fees. Laurent Greillier reports a relationship with Eli Lilly and Company that includes: funding grants and speaking and lecture fees. Laurent Greillier reports a relationship with Novartis that includes: funding grants and speaking and lecture fees. Laurent Greillier reports a relationship with AstraZeneca that includes: travel reimbursement. Etienne Martin reports a relationship with AstraZeneca that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Etienne Martin reports a relationship with Varian Medical Systems Inc that includes: speaking and lecture fees. Etienne Martin reports a relationship with Sanofi that includes: speaking and lecture fees. Etienne Martin reports a relationship with Ipsen that includes: speaking and lecture fees and travel reimbursement. Etienne Martin reports a relationship with MSD France SAS that includes: speaking and lecture fees. Etienne Martin reports a relationship with Janssen Pharmaceuticals Inc that includes: consulting or advisory and travel reimbursement. Sabine Ano reports a relationship with AstraZeneca that includes: employment. Marc Lefrancois reports a relationship with CMI Group that includes: employment and equity or stocks. Marc Lefrancois reports a relationship with AstraZeneca that includes: consulting or advisory. Alexis Cortot reports a relationship with Roche that includes: funding grants and paid expert testimony. Alexis Cortot reports a relationship with Novartis that includes: consulting or advisory, paid expert testimony, speaking and lecture fees, and travel reimbursement. Alexis Cortot reports a relationship with Sanofi that includes: speaking and lecture fees. Alexis Cortot reports a relationship with Pfizer that includes: paid expert testimony and speaking and lecture fees. Alexis Cortot reports a relationship with Takeda Pharmaceutical Company Limited that includes: paid expert testimony, speaking and lecture fees, and travel reimbursement. Alexis Cortot reports a relationship with Janssen Pharmaceuticals Inc that includes: paid expert testimony. If there are other authors, they 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 SPLF and Elsevier Masson SAS. All rights reserved.)

Background: Osimertinib, a third-generation tyrosine kinase inhibitor, is a new therapeutic option in epidermal growth factor receptor (EGFR)-mutated non-pretreated advanced non-small-cell lung cancer (NSCLC). The tumor escape mechanisms after first-line treatment with osimertinib are partially known; most of the data being obtained by analysis of circulating tumor DNA (ctDNA) from the FLAURA phase III trial., Study Design: The MELROSE study, a French multicentric, open label, phase II trial (ClinicalTrials.govNCT03865511) plans to enroll 150 patients with treatment-naive advanced EGFR-mutated (L858R or exon 19 deletion) NSCLC, age ≥ 18 years, with an Eastern Cooperative Oncology Group performance status 0 or 1. All patients will receive osimertinib at the dose of 80 mg/d. Tumor assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria will be performed every 3 months, with brain and thoracoabdominal computed tomographic scan. The continuation of osimertinib is at the discretion of the referring physician, particularly if clinical benefit is observed. The primary objective is the genetic tumor profile, both on tissue biopsy and ctDNA analyses, at the time of disease progression. Other endpoints include kinetic studies of ctDNA, biological progression-free survival (bPFS) (time from first study dose to first biological event on ctDNA), median PFS according to RECIST criteria 1.1 (called radiological [r] PFS), and median clinical (c) PFS (time from the first study dose to off-osimertinib). This study started in April 2019, and 18 centers in France are participants., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Lung cancer (LC) screening (LCS) with annual low-dose computed tomography scans has been seen to reduce the specific and overall mortality in selected populations. However, participation is key to successful screening programs. The EDIFICE (etude sur le dépistage des cancers et ses facteurs de compliance [survey on cancer screening and compliance factors]) nationwide observational surveys are used to assess behavior related to cancer screening programs in France., Materials and Methods: Using comprehensive multivariate stepwise logistic regression analyses of data from current and former cigarette smokers, we sought to identify the explanatory factors associated with the intention to participate in an LCS program., Results: Of the 1463 respondents with no personal history of cancer, 263 (36.4%) of the current cigarette smokers and 170 (26.3%) of the former cigarette smokers stated their willingness to participate in an LCS program. The explanatory factors differed between current cigarette smokers (already screened for LC: odds ratio [OR], 2.81; < 30 pack-years: OR, 2.69; intention to quit smoking: OR, 1.96; no social vulnerability: OR, 2.15) and former cigarette smokers (comorbidities: OR, 0.31). The usual eligibility criteria were not significantly explanatory., Conclusion: Our findings highlight the discrepancy that exists between target populations and individuals who actually intend to participate in a screening program for LC, with subsequent potential effects on the participation rates and, thus, on the efficacy of screening., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The COPD "frequent exacerbator" phenotype is usually defined by at least two treated exacerbations per year and is associated with a huge impact on patient health. However, existence of this phenotype and corresponding thresholds still need to be formally confirmed by statistical methods analyzing exacerbation profiles with no specific a priori hypothesis. The aim of this study was to confirm the existence of the frequent exacerbator phenotype with an innovative unbiased statistical analysis of prospectively recorded exacerbations., Methods: Data from patients with COPD from the French cohort in Exacerbations of COPD Patients (EXACO) were analyzed using the KmL method designed to cluster longitudinal data and receiver operating characteristic (ROC) curve analysis to determine the best threshold to allocate patients to identified clusters. Univariate and multivariate analyses were performed to study characteristics associated with different clusters., Results: Two clusters of patients were identified based on exacerbation frequency over time, with 2.89 exacerbations per year on average in the first cluster (n = 348) and 0.71 on average in the second cluster (n = 116). The best threshold to distinguish these clusters was two moderate to severe exacerbations per year. Frequent exacerbators had more airflow limitation, symptoms, and health-related quality of life impairment. A simple clinical score was derived to help identify patients at risk of exacerbations., Conclusions: These analyses confirmed the existence and clinical relevance of a frequent exacerbator subgroup of patients with COPD and the currently used threshold to define this phenotype., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

The patient information and obtaining their consent before any therapeutic constitute a basis for medicine exercise. However, there are situations where the physician may be in default. In that case, concepts of benefit/risk balance, of clear and appropriate information, and of legal liability for medico-surgical staff takes all their magnitude. That was the case in our observation, with a 69 years old patient with history of smoking, presenting a suspicious lung opacity which will require, following an agreement by multidisciplinary meeting, an exploration by thoracotomy despite an acceptable but altered respiratory function, as a result of a post-smoking broncho-emphysema. The non-malignant character of the suspected lesion raise questions about the risks involved, the benefit/risk balance, and the legal risk scopes of the medicosurgical staff as defined in the Cancer programme framework.