Rechallenge de l'immunothérapie dans les cancers bronchiques non à petites cellules de stade IV

International audienceImmune checkpoint inhibitors are the milestine of the first-line treatment of advanced non-small cell lung cancer (NSCLC) without oncogenic addiction. Despite a prolonged efficacy in a subset of patients, the majority of them will experience tumor progression with ICIs (primary or late progression). Because of a limited efficacy of treatments used in second line or more, it is logical to rause the potential interest of a rechallenge of ICIs. Despite a current limited knowledge of resistance mechanisms to ICIs, several restrospective studies have suggested the benefit of the rechallenge especially for pateints with good performance status, prolonged first course of ICIs, an initial interruption of ICIs due to immune toxicity (rather than tumor progression), and/or pateints who received a chemotherapy between the 2 courses of ICIs. Updated results from phase III trials with pembrolizumab in first line have also shown that, in case of rechallenge for patients with secondary progression after 2 years of pembrolizumab, the majority of them took benefit from this strategy. ICIs rechallenge after immune toxicity is feasible but should be discussed in dedicated multi-disciplinary board for each patient, according to the type of the first immune event and its severity

Infections virales chroniques (hépatites, VIH) et impact sur le choix thérapeutique

International audienceHepatitis B (HBV) and C (HCV) viral infections, and human immunodeficiency virus (HIV) infection are still largely under-screened in routine before the beginning of systemic treatment in lung cancer patients. These infections can however have several therapeutic implications, with notably the risk of viral reactivation and hepatitis flare (HBV, HCV), and the necessity of a specific anti(retro)viral treatment in many patients. Data from literature are scarce, but suggest an equivalent efficacy and toxicity profile of chemotherapy and immune checkpoint inhibitors compared to global population. A systematic screening of HBV, HCV and HIV infections is needed in all patients before any systemic treatment. Recommendations have been published for chronic HBV and HCV infections management in cancer patients. The cases of HIV patients with lung cancer should be discussed in the national board ONCOVIH. Inclusions in dedicated clinical trials are encouraged. 1877-1203Les infections à virus de l’hépatite B (VHB), hépatite C (VHC) et de l’immunodéficience acquise humaine (VIH) restent largement sous-dépistées en pratique avant traitement systémique d’un cancer bronchique. Les implications thérapeutiques sont nombreuses, avec notamment le risque de réactivation virale et d’hépatite aiguë (VHB, VHC), et la nécessité dans un certain nombre de cas d’instaurer un traitement spécifique anti(rétro) viral en début de prise en charge. Les données de la littérature sont parcellaires, mais semblent indiquer une efficacité et une tolérance de la chimiothérapie et des inhibiteurs de point de contrôle immunitaire comparable à la population générale. Il est actuellement recommandé de dépister systématiquement ces infections avant l’instauration de tout traitement anti-tumoral. Des recommandations existent pour la prise en charge des infections virales chroniques VHB et VHC sous traitement anti-cancéreux. Les dossiers des patients avec une infection VIH et un cancer bronchique devraient être discutées au sein de la RCP nationale ONCOVIH. Les inclusions dans des essais thérapeutiques dédiés doivent être encouragées

Acute generalized exanthematous pustulosis caused by gemcitabine after nivolumab in metastatic lung adenocarcinoma followed by a dramatic tumor response: A case report

International audienceHerein, we report a case of a 73-year-old female patient diagnosed with cT4N0M1a lung adenocarcinoma with KRAS G12C mutation, PDL1 < 1% and treated in fourth-line setting with gemcitabine after progression under nivolumab. After one infusion of gemcitabine, the patient presented with an acute worsening of general condition (performance status 4) with extensive skin lesions and fever, leading to hospitalization and diagnosis of acute generalized exanthematous pustulosis. Initial blood work revealed multiple organ failures with an important inflammatory syndrome. Patient state improved after intravenous hydration and local and systemic corticosteroids. The decision was made to stop systemic cancer treatment. Two months follow-up showed a remarkable response on all cancer localizations. Although immunotherapy is transforming cancer care, predicting response to immunotherapy remains challenging and resistant mechanisms remain mostly unknown. This case underlines that important immune-stimulation can lead to tumor response in a patient previously refractory to all antitumor treatments

La classification TNM en pratique

International audienceTherapeutic algorithm for lung cancer is depending on histology, patient's functional status and disease extent. The international TNM classification, accepted by both UICC and AJCC, is routinely used for non-small cell lung cancer management and is recommended for small cell lung cancer even though for the latter, the Veterans’ Administration classification is preferred for therapeutic decision. The aim of this article is to review the 8th TNM classification, its practical impact and the IASLC Staging Committee proposals regarding some specific clinical situations

Algorithme thérapeutique des cancers bronchiques à petites cellules de stade localisé

International audienceThis article describes the treatment strategies of localized small cell lung cancer. The modalities of pre-therapeutic evaluation, thoracic radiotherapy and prophylactic brain radiotherapy are presented. We discuss also the place of immune checkpoint inhibitor, surgery and thoracic stereotactic radiotherapy. 1877-120

La classification TNM en pratique

Therapeutic algorithm for lung cancer is depending on histology, patient's functional status and disease extent. The international TNM classification, accepted by both UICC and AJCC, is routinely used for non-small cell lung cancer management and is recommended for small cell lung cancer even though for the latter, the Veterans’ Administration classification is preferred for therapeutic decision. The aim of this article is to review the 8th TNM classification, its practical impact and the IASLC Staging Committee proposals regarding some specific clinical situations.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Les CBNPC de stades avancés hors addiction oncogénique: les traitements systémiques de deuxième ligne

International audienceThe emergence of immunotherapy as the cornerstone of first line therapy in advanced stage non-small cell lung cancer, without oncogenic driver, has led to change the treatment algorithm of second line, which was previously and mainly based on anti-PD(L)-1 given as a single agent. Second-line treatment is currently based on chemotherapy, with a platinum-based doublet for patients treated in first line by pembrolizumab alone, and standard second-line chemotherapy options for patients treated by chemotherapy-immunotherapy combinations, i.e. docétaxel regardless of histology or pemetrexed for non-squamous cell carcinoma when not used in first line. Addition of an antiangiogenic agent to docétaxel only achieved a modest improvement of overall survival but neither nintedanib, nor docétaxel is available in France. The future of second line treatment would require a better knowledge and understanding of resistance mechanisms to anti-PD(L)-1, and randomized phase III clinical trials, in order to optimize therapeutic options, including or not a rechallenge to an immunotherapy, targeting to restore anti-tumour immune response

Les difficultés de la classification TNM en pratique

info:eu-repo/semantics/publishe

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

Sequential ctDNA whole-exome sequencing in advanced lung adenocarcinoma with initial durable tumor response on immune checkpoint inhibitor and late progression

International audienceBACKGROUND: Despite prolonged tumor response to immune checkpoint inhibitors (ICIs) for a subset of patients with advanced non-small cell lung cancer (NSCLC), a secondary resistance will occur for a majority of these patients. The understanding of late progression mechanisms with ICIs is important to improve future treatment strategies. METHODS: We performed whole-exome sequencing (WES) on circulating tumor DNA and compared molecular profiles between the beginning of ICI treatment and tumor progression in patients with advanced NSCLC treated with ICIs and who had initial and prolonged tumor response with secondary progression, after at least 6 months of treatment. RESULTS: We identified eight patients who experienced initial and durable tumor response, and secondary tumor progression after 6 months of treatment, with available paired blood samples (diagnosis and progression). All had lung adenocarcinoma, three had programmed-death ligand-1 expression ≥50% in immunohistochemistry and all presented low blood tumor mutational burden (bTMB). Seven patients received nivolumab in second-line or more, and one received pembrolizumab as first-line treatment. WES at progression showed clonal selection with molecular alterations of Wnt pathway-related genes, increase of copy number aberrations in cancer-related genes and loss of tumor-suppressor genes (such as PTEN) or of genes associated with immune response (such as B2M). No difference in term of bTMB was observed at progression. CONCLUSIONS: This is the first study describing putative molecular mechanisms associated with late progression under ICI in lung cancer. Studies on treatment strategies adapted to these mechanisms are needed