Réanimation et cancer du poumon

L admission des patients atteints de cancer du poumon en réanimation fait toujours débat. Le mauvais pronostic de ces patients est souvent mis en avant.Tous les patients consécutifs atteints de cancer du poumon et séjournant plus de 24h en réanimation entre janvier 2003 et décembre 2010 ont été inclus dans une étude rétrospective. 104 patients ont été inclus avec un SAPS 2 médian de 54,5 ; 52% étaient métastatiques à l admission en réanimation. 55 (53%) patients ont été intubés et ventilés de manière invasive. Les taux de mortalité en réanimation, à l hôpital, à 1 an et 3 ans sont respectivement de 31,7%, 48%, 83,7%, 98%. Les facteurs de mauvais pronostic mis en évidence sont le score SAPS 2 >= 42 (OR 2,65 IC 95% (1,10-6,36), p=0,03), la ventilation mécanique (OR 4,88 IC 95% (1,86- 12,76), p=0,012), l utilisation des vasopresseurs (OR 6,26 IC95% (2,52- 15,57), p<0,001) et la nécessité d une suppléance d organe (ventilation non-invasive, ventilation mécanique invasive, vasopresseurs, dialyse) (OR 5,5 IC95% (1,12- 27,2), p=0,0002). 75% des patients sortis vivants de l hôpital après l hospitalisation en réanimation auront un traitement spécifique du cancer du poumon.Le pronostic du patient atteint de cancer du poumon hospitalisé en réanimation dépend de la gravité de la pathologie qui l amène en réanimation et non de sa maladie sous-jacente.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Histomolecular Resistance Mechanisms to First-Line Osimertinib in EGFR-Mutated Advanced Non-Small Cell Lung Cancer: A Multicentric Retrospective French Study

International audienceBackground: Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) used in first line for the treatment of advanced EGFR-mutated non-small cell lung cancer (NSCLC). Objective: The identification of related histomolecular resistance mechanisms to first-line osimertinib is a critical step to define the optimal treatment strategy beyond progression. Patients and Methods: All consecutive patients treated in the first line with osimertinib for advanced EGFR-mutated NSCLC at 10 hospitals in the Greater Paris area between April 2015 and January 2021 were included. Histomolecular data from plasma and tissue samples taken at progression under osimertinib were collected, and all samples were analyzed using DNA next-generation sequencing. Data on objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and time to treatment discontinuation (TTD) were also collected. Results: Overall, 104 patients were included. Most patients had adenocarcinoma (n = 102, 98%) with an exon 19 EGFR deletion (n = 54, 52%). Forty-two patients (50%) had central nervous system (CNS) metastasis at the time of osimertinib initiation. ORR was 76%, median PFS and OS were 12.6 months and 52 months, respectively, and TTD was 33 months. At the time of analysis, 44 patients (42%) had tumor progression, and among these patients, 27 (61%) contributive samples were available. The most frequent molecular alterations at progression were mesenchymal epithelial transition factor (MET) amplification (15%; n = 4) and EGFR C797S mutation (11%; n = 3). Histological transformation was found in one patient (4%). RNA next-generation sequencing was performed in eight patients and showed a CCDC6-RET fusion in one patient (12%). Conclusions: We confirmed the efficacy of osimertinib in patients with advanced EGFR mutation-positive NSCLC. At progression, the most frequent histomolecular alterations were MET amplification and EGFR C797S mutation

Efficacité et tolérance du brigatinib chez des patients pris en charge pour un cancer bronchopulmonaire non à petite cellules avec translocation ALK en France. Etude BRIGALK.

National audienceBrigatinib is a next-generation ALK inhibitor initially developed in ALK-positive NSCLC pretreated with crizotinib

Brigatinib for Pretreated, ALK-Positive, Advanced Non-Small-Cell Lung Cancers: Long-Term Follow-Up and Focus on Post-Brigatinib Lorlatinib Efficacy in the Multicenter, Real-World BrigALK2 Study

Brigatinib is a next-generation ALK inhibitor (ALKi) that shows efficacy in ALK inhibitor na&iuml;ve and post-crizotinib ALK+ advanced NSCLCs (aNSCLCs). The efficacy of brigatinib was retrospectively assessed in patients with aNSCLCs included in the brigatinib French Early-Access Program (1 August 2016&ndash;21 January 2019). The primary endpoint was investigator-assessed progression-free survival (invPFS) and the primary analysis was updated in 2021 with a longer follow-up, focused on post-brigatinib lorlatinib efficacy. Sixty-six centers included 183 patients: median age 60 &plusmn; 12.7 years; 78.3% never/former smokers; median of 3 &plusmn; 1 previous lines and 2 &plusmn; 0.5 ALKis; 37.1% ECOG PS 2 and 55.6% &gt;3 metastatic sites. The median follow-up from brigatinib initiation was 40.4 months (95% CI 38.4&ndash;42.4). InvPFS was 7.4 months (95% CI 5.9&ndash;9.6), median duration of treatment (mDOT) was 7.3 months (95% CI 5.8&ndash;9.4) and median overall survival (mOS) was 20.3 months (95% CI 15.6&ndash;27.6). The median DOT and OS from brigatinib initiation tend to decrease with the number of ALK inhibitors used in previous lines of therapy. Based on the data collected, 92 (50.3%) patients received &ge;1 agent(s) post-brigatinib and 68 (73.9%) of them received lorlatinib, with 51 (75%) immediately receiving it post-brigatinib, 12 (17.6%) receiving it after one and 5 (7.4%) after &ge;2 subsequent treatments. The median follow-up was 29.9 (95% CI 25.7&ndash;33.1) months. Lorlatinib mDOT was 5.3 (95% CI 3.6&ndash;7.6) months with a median OS from lorlatinib initiation of 14.1 (95% CI 10.3&ndash;19.2) months. The results of the brigALK2 study confirm the efficacy of brigatinib in a population of heavily pretreated ALK+ aNSCLC patients and provide new data on the activity of lorlatinib after brigatinib

Brigatinib for Pretreated, ALK-Positive, Advanced Non-Small-Cell Lung Cancers: Long-Term Follow-Up and Focus on Post-Brigatinib Lorlatinib Efficacy in the Multicenter, Real-World BrigALK2 Study

International audienceBrigatinib is a next-generation ALK inhibitor (ALKi) that shows efficacy in ALK inhibitor naïve and post-crizotinib ALK+ advanced NSCLCs (aNSCLCs). The efficacy of brigatinib was retrospectively assessed in patients with aNSCLCs included in the brigatinib French Early-Access Program (1 August 2016–21 January 2019). The primary endpoint was investigator-assessed progression-free survival (invPFS) and the primary analysis was updated in 2021 with a longer follow-up, focused on post-brigatinib lorlatinib efficacy. Sixty-six centers included 183 patients: median age 60 ± 12.7 years; 78.3% never/former smokers; median of 3 ± 1 previous lines and 2 ± 0.5 ALKis; 37.1% ECOG PS 2 and 55.6% >3 metastatic sites. The median follow-up from brigatinib initiation was 40.4 months (95% CI 38.4–42.4). InvPFS was 7.4 months (95% CI 5.9–9.6), median duration of treatment (mDOT) was 7.3 months (95% CI 5.8–9.4) and median overall survival (mOS) was 20.3 months (95% CI 15.6–27.6). The median DOT and OS from brigatinib initiation tend to decrease with the number of ALK inhibitors used in previous lines of therapy. Based on the data collected, 92 (50.3%) patients received ≥1 agent(s) post-brigatinib and 68 (73.9%) of them received lorlatinib, with 51 (75%) immediately receiving it post-brigatinib, 12 (17.6%) receiving it after one and 5 (7.4%) after ≥2 subsequent treatments. The median follow-up was 29.9 (95% CI 25.7–33.1) months. Lorlatinib mDOT was 5.3 (95% CI 3.6–7.6) months with a median OS from lorlatinib initiation of 14.1 (95% CI 10.3–19.2) months. The results of the brigALK2 study confirm the efficacy of brigatinib in a population of heavily pretreated ALK+ aNSCLC patients and provide new data on the activity of lorlatinib after brigatinib

Safety and Patient-Reported outcomes of atezolizumab plus chemotherapy with or without bevacizumab in stage IIIB/IV non-squamous non-small cell lung cancer with EGFR mutation, ALK rearrangement or ROS1 fusion progressing after targeted therapies (GFPC 06-2018 study)

International audienceBackground: In an open-label multicenter non-randomized non-comparative phase II study in patients with stage IIIB/IV non-squamous non -small cell lung cancer (NSCLC), oncogenic addiction (EGFR mutation or ALK/ROS1 fusion), with disease progression after tyrosine-kinase inhibitor and no prior chemotherapy (NCT04042558), atezolizumab, carboplatin, pemetrexed with or without bevacizumab showed some promising result. Beyond the clinical evaluation, we assessed safety and patient-reported outcomes (PROs) to provide additional information on the relative impact of adding atezolizumab to chemotherapy with and without bevacizumab in this population. Materials: Patients received platinum-pemetrexed-atezolizumab-bevacizumab (PPAB cohort) or, if not eligible, platinum-pemetrexed-atezolizumab (PPA cohort). The incidence, nature, and severity of adverse events (AEs) were assessed. PROs were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-Core 30 and EORTC QLQ-Lung Cancer 13). Result: Overall, 68 (PPAB) and 72 (PPA) patients were evaluable for safety. Grade 3 -4 AEs occurred in 83.8% (PPAB) and 63.9% (PPA). Grade 3 -4 atezolizumab-related AEs occurred in 29.4% and 19.4%, respectively. Grade 3 -4 bevacizumab-related AEs occurred in 36.8% (PPAB). Most frequent grade 3 -4 AEs were neutropenia (19.1% in PPAB; 23.6% in PPA) and asthenia (16.2% in PPAB; 9.7% in PPA). In PPAB, we observed a global stability in global health security (GHS) score, fatigue and dyspnea with a constant tendency of improvement, and a significant improvement in cough. In PPA, we observed a significant improvement in GHS score with a significant improvement in fatigue, dyspnea and cough. At week 54, we observed an improvement from baseline in GHS score for 49.2% of patients. In both cohorts, patients reported on average no clinically significant worsening in their overall health or physical functioning scores. Conclusion: PPAB and PPA combinations seem tolerable and manageable in patients with stage IIIB/IV nonsquamous NSCLC with oncogenic addiction (EGFR mutation or ALK/ROS1 fusion) after targeted therapies

Additional file 1 of ICU admission for solid cancer patients treated with immune checkpoint inhibitors

Additional file 1: Table S1. World Health Organization-Uppsala Monitoring Centre (WHO-UMC) causality categories. Table S2. Diagnosis at ICU admission according to proposed IrAE causality at ICU discharge (n = 110 patients)

Aide à la décision de transfert ou non transfert en réanimation d’un patient atteint de cancer

Référentiel inter régional en soins oncologiques de support, AFSOS et Réseau Espace Santé - Cancer Rhône-Alpes (RRCRA), 201