BACKGROUND:Most patients with lung cancer have comorbidities at the time of diagnosis. Treatments prescribed for cancer-related symptoms are thus added to drugs for chronic diseases. The impact of comedication on immunotherapy efficacy has been studied in retrospective series, but the results are often biased by the lack of information on the independent prognostic impact of comedication weighted for comorbidities and disease aggressiveness. METHODS:The IFCT-1502 CLINIVO study is a nationwide retrospective cohort of patients with advanced non-small cell lung cancer who received nivolumab in second or later lines of treatment as part of the French Expanded Access Program. We retrieved comedication prescriptions from 90 days before to 30 days after the first nivolumab administration via the French national healthcare database. We report the results of a comprehensive post hoc analysis investigating the impact of comedication on treatment response considering well-known negative prognostic factors. RESULTS:We selected 753 patients whose medical and comedication records were available. According to the multivariate analysis, morphine and corticosteroids > 20 mg per day were associated with poor overall survival regardless of disease aggressiveness. Conversely, metformin was associated with better overall survival. Morphine and corticosteroids were also found to be associated with shorter real-world progression-free survival according to multivariate analysis, as were poor prognostic factors such as liver metastasis and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score ≥ 2. CONCLUSION:Our study confirmed the negative impact of morphine and high-dose corticosteroids on immunotherapy efficacy regardless of poor prognostic factors related to disease aggressiveness. On the other hand, our findings suggested a positive impact of metformin on immunotherapy outcomes.

Supplementary materials - substudy 1 statistical report

Background Capmatinib has previously shown activity in treatment-naive and previously treated patients with non- small-cell lung cancer (NSCLC) and a MET exon 14-skipping mutation (METex14). MET ex14). Here, we report the final outcomes from the phase 2 GEOMETRY mono-1 study with an aim to provide further evidence for the activity of capmatinib. Methods In this non-randomised, multi-cohort, open-label, phase 2 trial conducted in 152 centres and hospitals in 25 countries, with patients treated in 95 centres in 20 countries, eligible patients (aged >= 18 years) with MET-dysregulated, EGFR wild-type, and ALK rearrangement-negative advanced NSCLC (stage IIIB/IV) and an Eastern Cooperative Oncology Group performance status of 0 or 1 were assigned to cohorts (1a, 1b, 2, 3, 4, 5a, 5b, 6 and 7) based on their MET status (METex14 MET ex14 or MET amplification) and previous therapy lines. Patients received capmatinib (400 mg orally twice daily) in 21-day treatment cycles. The primary endpoint was overall response rate by blinded independent central review per Response Evaluation Criteria in Solid Tumours version 1.1 and was performed on the full analysis set (all patients who received at least one dose of capmatinib). Previous reports of this study had published interim or primary data for cohorts 1-7. Here, we report the final clinical outcomes from all MET ex14 cohorts (4, 5b, 6, and 7) and safety from all study cohorts (1-7). The trial is registered with ClinicalTrials.gov, NCT02414139, and has been completed. Findings Of 373 treated patients enrolled from June 11, 2015, to March 12, 2020, 160 (97 [61%] female) patients had MET ex14 NSCLC and were enrolled in four cohorts: 60 treatment-naive (cohorts 5b and 7) and 100 previously treated (cohorts 4 and 6). The overall median study follow-up was 464 months (IQR 418-654) for the treatment-na & iuml;ve patients and 669 months (567-739) for previously treated patients, respectively. Overall responses were recorded in 41 (68%; 95% CI 550-797) of 60 treatment-naive patients and 44 (44%; 95% CI 341-543) of 100 previously treated patients. In all 373 treated patients, the most common treatment-related adverse events were peripheral oedema (n=174; 47%), nausea (n=130; 35%), increased blood creatinine (n=78; 21%), and vomiting (n=74; 20%). Grade 3-4 serious adverse events occurred in 164 (44%) patients, dyspnoea being the most common (18 patients [5%]). Treatment-related deaths occurred in four (1%) patients (one each of cardiac arrest, hepatitis, organising pneumonia, and pneumonitis). No new safety signals were reported. Interpretation These long-term results support MET ex14 as a targetable oncogenic driver in NSCLC and add to the evidence supporting capmatinib as a targeted treatment option for treatment-naive and previously treated patients with MET ex14 NSCLC.

Introduction Oral folic acid supplementation is essential for patients treated with pemetrexed, to prevent the risk of severe hematologic toxicity. In case of intestinal absorption disorder, no recommendations exist for intravenous folic acid supplementation. Case report We describe a 74-year-old patient with multimetastatic non-small-cell lung adenocarcinoma, receiving first-line chemotherapy with carboplatin AUC5, pemetrexed 500 mg/m 2 and pembrolizumab 200 mg intravenously every 3 weeks. The patient presented neglected celiac disease, resulting in malabsorption syndrome with iron and folic acid deficiency. The question was how to administer folic acid supplementation during the pemetrexed-based chemotherapy. Management and outcomes Intravenous injection of 200 mg levoleucovorin on day 1 of cycle 1 of pemetrexed-based chemotherapy was administered and well tolerated. During the second cycle, the levoleucovorin perfusion was not renewed by omission. The patient was hospitalized for 7 days because of febrile aplasia. Piperacillin–tazobactam was started, and then switched to amoxicillin–clavulanate plus ciprofloxacin. After this episode of post-chemotherapy febrile aplasia, it was decided to systematically supplement the patient with intravenous levoleucovorin, with blood folate concentration monitoring at each cycle. At 16 months after start of treatment, the patient was in complete remission, indicating that the immune-chemotherapy was effective, with no further febrile neutropenia. Discussion/conclusion This case report highlights intravenous levoleucovorin supplementation as an alternative to oral folic acid if needed during pemetrexed–antifolate-based chemotherapy.

Supplementary Table S1: Best response rates for primary tumors and metastases in 67 patients (ITT population) treated with bevacizumab plus paclitaxel and carboplatin

Supplemental Figure S1. Sample inclusion flow chart. Supplemental Figure S2. Boxplot of circulating free DNA concentration in plasma (in ng/microl) regarding M stage (up), and number of metastatic sites (down) in all samples (n=106). Y axis is in logarithmic scale. Supplemental Table S1. Processes used in the different participating labs for tumor DNA extraction, storage, shipment, and biomarker analysis. Supplemental Table S2. Primers used for amplicon sequencing by IonTorrent next-generation sequencing Supplemental Table S3. Multiplex reaction conditions. Supplemental Table S4. NGS mutation screening results in the 68 paired samples Supplemental Table S5. IonTorrent NGS test results in cfDNA, for each individual amplicon and overall, taking tDNA as a reference and restricted to stage IV samples (n=50). Supplemental Table S6. NGS test results in tDNA and cfDNA for all amplicons concomitantly using the ITVC strategy (5A), or the in-house strategy (5B); and corresponding calculated sensitivity for all matched samples analyzed by NGS (n=68)

Introduction: The objective of this study was to assess the cost-effectiveness of atezolizumab versus best supportive care (BSC) as adjuvant treatment following resection and platinum-based chemotherapy for patients with stage II-IIIA non-small cell lung cancer (NSCLC) whose tumours have a programmed death-ligand 1 (PD-L1) expression & GE; 50% of tumour cells and excluding those with ALK/EGFR mutations, from a French collective perspective. Material and Methods: A five state Markov model over a 20-year time horizon was considered, including diseasefree survival (DFS1) from IMpower010 trial, three progression states (locoregional recurrence, first and secondline metastatic recurrence) and death. Utilities, quality-adjusted life year (QALY) decrements associated to adverse events, costs, resource use, and transition probabilities were considered in the model. These inputs were sourced from IMpower010 trial, literature, and clinical experts' opinion. Model uncertainty was assessed through deterministic, probabilistic sensitivity analyses and scenario analyses. Results: Atezolizumab was associated with a QALY gain of 1.662, mainly driven by additional time spent in the DFS state, and a life-year gain of 2.112 years. The incremental cost-effectiveness ratio (ICER) for atezolizumab versus BSC was euro21,348/QALY gained. The sensitivity analyses highlighted that uncertainty within the model had limited impact on results. Changing the DFS survival curves to other plausible distributions produced ICERs below euro20,000/QALY. Introducing an increasing proportion of cured patients (91.5%) from year two to year five reduced the ICER to euro13,083/QALY, while including a loss of efficacy at year two in the atezolizumab treatment arm increased the ICER to euro33,755/QALY. Discussion: Atezolizumab as adjuvant treatment in stage II-IIIA NSCLC resected patients with PDL1 & GE; 50% and without ALK/EGFR mutations has a lower ICER than other oncology drugs in France and a similar ICER to other adjuvant treatment in oncology.

In this retrospective study, MET inhibitor therapy demonstrated better survival outcomes compared with other treatments like chemotherapy and immunotherapy. Furthermore, MET ex14 skipping mutations and/or MET amplification typically occurred in the absence of other oncogenic driver mutations. With recent approvals of METi for patients with MET ex14 NSCLC, there is a need to identify more patients for treatment with METi to improve survival outcomes. Background: We evaluated the disease and patient characteristics, treatment, and MET testing patterns, predictive biomarkers and survival outcomes in patients with MET -dysregulated metastatic non-small-cell lung cancer (NSCLC) in a real-world setting. Patients and Methods: This was a multinational, retrospective, noninterventional chart review study. Data from medical records of patients with advanced/metastatic EGFR wild-type, MET -dysregulated NSCLC (December 2017-September 2018) were abstracted into electronic data collection forms. Results: Overall, 211 patient charts were included in this analysis; 157 patients had MET exon 14 skipping mutations ( MET ex14; with or without concomitant MET amplification) and 54 had MET amplification only. All patients were tested for MET ex14, whereas MET amplification was evaluated in 168 patients. No overlap was reported between MET dysregulation and ALK, ROS1 or RET rearrangements, or HER2 exon 20 insertions. Overall, 56 of 211 patients (26.5%) received MET inhibitor (METi) therapy in any treatment-line setting (31.2% in the MET ex14 cohort; 13% in the MET -amplified only cohort). In the MET ex14 cohort, median OS in patients receiving METi was 25.4 months versus 10.7 months in patients who did not (HR [95% CI]: 0.532 [0.340-0.832]; P = .0055). In the MET -amplified only cohort, median OS was 20.6 months in patients treated with METi compared with 7.6 months in those without METi (HR [95% CI]: 0.388 [0.152-0.991]; P = .0479). Conclusions: MET alterations in NSCLC typically occur in the absence of other oncogenic driver mutations and are associated with poor survival outcomes. Notably, METi therapies are associated with improved survival outcomes in patients with MET -dysregulated NSCLC.

Depuis la révolution des immunothérapies anti-cancéreuses par inhibiteurs de checkpoint et l’élargissement de leurs indications, de plus en plus de patients présentent des effets indésirables immuno-induits, notamment rhumatologiques tels que l’arthrite inflammatoire. La prise en charge des effets indésirables immuno-induits rhumatologiques peut s’avérer difficile nécessitant l’usage de traitements anti-inflammatoires tels que les corticoïdes, et les disease-modifiying antirheumatic drugs (DMARD) synthétiques (cs-) ou biologiques (b-). Ces traitements peuvent potentiellement limiter l’efficacité anticancéreuse de l’immunothérapie. L’objectif de notre travail était d’évaluer l’impact des traitements de l’effet indésirable immuno-induit rhumatologique sur l’évolution oncologique. Nous avons mené une étude observationnelle rétrospective monocentrique au sein de notre centre hospitalo-universitaire. Les patients éligibles étaient des patients adultes traités par immunothérapie et adressés à des rhumatologues pour un effet immuno-induit rhumatologique. Les patients présentant un rhumatisme inflammatoire actif avant le début de l’immunothérapie et n’ayant pas été évalués par un rhumatologue ont été exclus. Les données ont été obtenues à partir des dossiers médicaux en utilisant une collecte de données standardisée. Entre juillet 2016 et octobre 2022, 71 patients ont été inclus. Les patients ont été répartis en 3 groupes en fonction de leur traitement rhumatologique: traitement symptomatique par analgésiques ou anti-inflammatoires non stéroïdiens (AINS, n = 12), corticoïdes systémiques (n = 34) ou csDMARD et/ou bDMARD (n = 25). Aucune différence significative n’a été retrouvée entre les différents groupes en ce qui concerne la survie globale (p = 0,43) ou la survie sans progression (p = 0,46). Nous avons cherché à identifier de potentiels facteurs pronostiques dans chaque groupe. Un délai plus court entre l’apparition de l’effet indésirable immuno-induit et l’initiation d’un bDMARD était corrélé à une survie globale réduite (R = 0,88, p < 0,0001). Vu ce résultat, nous avons ensuite comparé les patients traités précocement par DMARD (< 6 semaines après l’effet immuno-induit, n = 9) avec un groupe contrôle (n = 50) composé des patients traités par DMARD introduit plus tardivement et des patients traités par corticoïdes. L’analyse de survie réalisée entre le groupe DMARD précoce et le groupe contrôle n’a pas montré de différence significative pour la survie globale (p = 0,79), mais la survie sans progression était plus faible dans le groupe DMARD précoce que dans le groupe contrôle (p = 0,048). Notre travail suggère des précautions quant à l’introduction précoce de DMARDs dans les 6 semaines après l’apparition de l’effet immuno-induit. Nos données supportent également les mises en garde énoncées précédemment dans la littérature concernant le risque plus élevé de progression cancéreuse lorsque l’effet immuno-induit est traité par bDMARD.

Background and Objectives: Cancer patients undergoing cytotoxic chemotherapies exhibit a series of adverse side effects including smell and taste alterations, which can have a significant impact on their food behavior and quality of life. Particularly, olfactory alterations are often underestimated, although declared as frequent by cancer patients. In the present study, we set out to examine loss of smell in lung cancer patients undergoing chemotherapy and its relationship to food habits.Material and Methods: Forty-four bronchial cancer patients receiving cisplatin and 44 controls age and gender matched participants were tested for olfactory and gustatory functions using the European Test of Olfactory Capabilities and the Taste Strips test. Participants reported their food and dietary habits by filling a self-administered questionnaire. Patients were tested under two different sessions: i)before the beginning of the treatment, and ii) 6 weeks later, after 2 cycles of chemotherapy. Controls were tested under the same protocol with two sessions separated by 6 weeks.Results and Conclusions: The results highlighted decreased smell and taste abilities in almost half of the lung patients’ group even before the exposition to Cisplatin. On a perceptual level, patients rated typical food odors as less edible compared to controls. Moreover, within the patients’ group, hyposmics reported using more condiments, possibly as a compensatory mechanism to their decreased sensory abilities. Taken together, these findings showed that loss of smell is prevalent in lung cancer patients and is related to changes in dietary practices including seasoning. Future studies will provide a better understanding of these sensory compensation mechanisms associated with olfactory loss and their effects on food pleasure in this patient population.

BACKGROUND:In COVID-19 patients, older age (sixty or older), comorbidities, and frailty are associated with a higher risk for mortality and invasive mechanical ventilation (IMV) failure. It therefore seems appropriate to suggest limitations of care to older and vulnerable patients with severe COVID-19 pneumonia and a poor expected outcome, who would not benefit from invasive treatment. HFNO (high flow nasal oxygen) is a non-invasive respiratory support device already used in de novo acute respiratory failure. The main objective of this study was to evaluate the survival of patients treated with HFNO outside the ICU (intensive care unit) for a severe COVID-19 pneumonia, otherwise presenting limitations of care making them non-eligible for IMV. Secondary objectives were the description of our cohort and the identification of prognostic factors for HFNO failure. METHODS:We conducted a retrospective cohort study. We included all patients with limitations of care making them non-eligible for IMV and treated with HFNO for a severe COVID-19 pneumonia, hospitalized in a COVID-19 unit of the pulmonology department of Lyon Sud University Hospital, France, from March 2020 to March 2021. Primary outcome was the description of the vital status at day-30 after HFNO initiation, using the WHO (World Health Organization) 7-points ordinal scale. RESULTS:Fifty-six patients were included. Median age was 83 years [76.3-87.0], mean duration for HFNO was 7.5 days, 53% had a CFS score (Clinical Frailty Scale) >4. At day-30, 73% of patients were deceased, one patient (2%) was undergoing HFNO, 9% of patients were discharged from hospital. HFNO failure occurred in 66% of patients. Clinical signs of respiratory failure before HFNO initiation (respiratory rate >30/min, retractions, and abdominal paradoxical breathing pattern) were associated with mortality (p = 0.001). CONCLUSIONS:We suggest that HFNO is an option in non-ICU skilled units for older and frail patients with a severe COVID-19 pneumonia, otherwise non-suitable for intensive care and mechanical ventilation. Observation of clinical signs of respiratory failure before HFNO initiation was associated with mortality.

Low molecular weight heparins (LMWH) and anti-Xa direct oral anti-coagulants (DOACs) are recommended for the long-term treatment of cancer-associated thrombosis (CAT) based on well-documented randomised controlled trials. Anti-Xa DOACs are viewed as a first choice for the treatment of patients with CAT. A large number of drug–drug interactions have been reported between DOACs and chemotherapy drugs, modifying circulating levels of DOAC leading to fears of increased bleeding risks or thrombotic recurrence. Progresses in anti-neoplastic therapies have improved the prognosis and the survival, thus increasing the prevalence of frail patients with cancer. However, since frailties tend to be excluded from large trials due to multiple co-morbidities, current guidelines are not fully applicable to this population. The management of these frail patients with CAT is particularly complex and requires a risk assessment on a case-by-case basis with specific focus on cancer, patient-related risk factors and drug–drug interactions. In this brief review we have identified age, co-morbidities and co-medications as key factors of frailty that require careful attention and we have developed a therapeutic decision algorithm to help clinicians optimising the use of anti-coagulants in patients with cancer with CAT, especially in case of anti-Xa DOACs concomitant medications. With the evaluation of the bleeding risk according to the type of cancer, and anticipating drug–drug interactions intensity, taking into account patient frailties allows the optimisation of the anti-coagulant choice. A systematic collaboration between oncologists, vascular pathology specialists and pharmacists is warranted to ensure an optimal patient management. Clinical studies are needed to determine the real impact of these interactions.

Appendix Methods and Materials, Tables 1-4, Figures 1-3. Appendix Table 1: Characteristics of patients at baseline Appendix Table 2: Best response rates for primary tumors and metastases in 24 patients treated with second-line bevacizumab plus erlotinib Appendix Table 3: PFS, OS, and response rates according to EGFR mutation status in 24 patients treated with second-line bevacizumab plus erlotinib Appendix Table 4: Overview of AEs in 24 patients treated with second-line bevacizumab plus erlotinib Appendix Figure 1. Response rates for patients treated with second-line bevacizumab plus erlotinib. Appendix Figure 2. Waterfall plots of best overall response for patients treated with second-line bevacizumab plus erlotinib. Appendix Figure 3. Kaplan-Meier curves for second-line treatment with bevacizumab plus erlotinib.

Supplementary Figure from Comprehensive Genome Profiling in Patients With Metastatic Non–Small Cell Lung Cancer: The Precision Medicine Phase II Randomized SAFIR02-Lung Trial

Purpose: The objective of this study was to describe filgrastim biosimilar-Sandoz modalities of use in patients receiving cytotoxic chemotherapy regimens with a rest period of <= 14 days and to investigate the incidence of febrile neutropenia (FN) in routine clinical practice. Methods: This was a French, multicenter, prospective and descriptive, non-interventional study including patients with breast, lung, gastrointestinal cancer or a lymphoma initiating filgrastim biosimilar-Sandoz treatment and in the context of cytotoxic chemotherapy with a rest period not exceeding 14 days. Data were collected during two routine clinical visits on the modalities of use of filgrastim biosimilar-Sandoz, on the incidence of neutropenia events and on adverse events. Results: Between November 2015 and June 2018, 1080 patients were enrolled in the study in 129 centers. Overall, 941 patients were evaluable for efficacy and 937 for safety. Of the 941 patients, 84.8% had a solid tumor and 15.2% had a lymphoid hemopathy. Filgrastim biosimilar-Sandoz was prescribed as primary prophylaxis in 74.0% of the patients and as secondary prophylaxis in 22.4% of the patients. FN was reported in 1.5% of patients with a solid tumor and 12.6% of patients with a lymphoma. A chemotherapy relative dose intensity of over 85% with regard to the reference dose was achieved by more than 80% of the patients in all tumor localizations. Conclusions: The study showed that filgrastim biosimilar-Sandoz is safe to use and effective in preventing FN and in allowing to maintain the dose intensity of chemotherapy.

Les patients métastatiques osseux ont un mauvais pronostic et une altération de leur qualité de vie avec la survenue d'événements osseux. Le denosumab (DMAB), est un anticorps monoclonal humain qui cible le RANKL. Il est utilisé pour la prévention des événements osseux chez les patients métastatiques osseux. L'axe RANK/RANKL est également impliqué dans de nombreux processus immunologiques. Du fait de l'utilisation croissante en oncologie des inhibiteurs des checkpoints immunitaire (ICI) qui suppriment les mécanismes d'inhibition du système immunitaire induits par les tumeurs, il est licite d'analyser l'éventuel effet synergique anti-tumoral entre les ICI et le DMAB. En effet, certains cas cliniques, cohortes de patients et études in vivo suggèrent cette synergie tout comme l'importance de la séquence d'administration entre le DMAB et l'ICI. Nous avons utilisé la base de données rétrospective IMMUCARE, développée au sein de notre centre hospitalier universitaire, des patients présentant une tumeur solide traitée par ICI (2014–2022). Pour être inclus dans cette analyse, les patients devaient présenter des métastases osseuses. Nous avons analysé la survie globale, la survie sans progression et le changement de ligne de traitement dans les différents groupes suivants : pas de DMAB, association ICI + DMAB, séquence ICI puis DMAB, et séquence DMAB puis ICI. Les survies ont aussi été analysées en multivariée (modèle de Cox). Au total, 268 patients (28,3 % de femmes) présentant des métastases osseuses ont pu être inclus dans l'étude. L'âge moyen ± DS était de 65,5 ± 4,6 ans. Il s'agissait essentiellement de patients atteints de cancer du poumon (n = 223 ; 83,2 %) et de mélanome (n = 18 ; 6,7 %). La survie globale moyenne était de 8,3 mois et la survie sans progression de 4,7 mois. Nous n'avons pas trouvé de différence significative en ce qui concerne la survie globale et la survie sans progression entre les patients sous DMAB + ICI versus sous ICI seul (p = 0,29). Il existait une différence significative pour le délai de changement de ligne de traitement oncologique en faveur de la séquence ICI puis DMAB (3,6 mois vs 8,6 mois en survie globale médiane ; p = 0,022). Il existait aussi une moins bonne survie globale et de survie sans progression des patients recevant une corticothérapie supérieure à 10 mg/j (survie globale médiane 3,2 mois vs 7,8 mois ; p = 0,001). Le résultat est maintenu en analyse multivariée (p = 0,001). Dans cette étude nous ne montrons pas de bénéfice à l'utilisation de DMAB avec ICI sur la survie globale et sur la survie sans progression. Il existe comme dans les études in vivo, un signal bénéfique en faveur de l'utilisation du DMAB après les ICI chez les patients métastatiques osseux. Ce résultat devra être confirmé par d'autres. Comme dans les cohortes de patients non métastatiques osseux traités par ICI, nous montrons un effet néfaste de l'utilisation d'une corticothérapie supérieure à 10 mg/j au moment de l'introduction d'ICI.

Le cancer bronchique reste le premier pourvoyeur de métastases cérébrales (MC), responsables d’une importante morbidité et mortalité. De plus, la réponse cérébrale aux traitements systémiques est inconstante et imprévisible. Ceci peut être lié à l’hétérogénéité moléculaire connue entre MC et tumeur primitive, mais également aux spécificités de la barrière hémato-encéphalique et du microenvironnement cérébral. Nous avons mené une étude à partir des données de l’essai de phase II randomisé SAFIR-02 Lung. Notre objectif principal était de comparer les profils moléculaires des patients avec et sans MC. Notre objectif secondaire était d’évaluer la réponse intra-cérébrale en fonction du traitement de maintenance reçu, et du statut cérébral à l’inclusion. Un total de 365 patients screenés dans l’essai SAFIR-02 Lung disposant de données moléculaires interprétables ont été inclus dans cette analyse. Les données cliniques et biologiques ont été recueillies. Les analyses génomiques reposaient sur la l’hybridation génomique comparative et le séquençage de nouvelle génération (NGS) suivant les recommandations du protocole. Les analyses génomiques initiales ont permis d’identifier une signature de 12 gènes (renforcée par 12 gènes adjacents), spécifique des cancers bronchiques avec MC. Tous les gènes identifiés avaient été précédemment décrits comme impliqués dans l’oncogenèse (TNS1, PAK2, COBL, CDK5, GLRX3, WNT5B, SETD1B, EGLN3, TOX3, RYR1, PVR et BCL2L1). Les analyses en NGS ont retrouvé une proportion plus importante de mutations de KRAS dans le groupe porteur de métastases cérébrales (44,3 % versus 32,3 %), particulièrement de mutation G12 C (63 % versus 47 %). De plus, l’analyse des interactions protéiques a mis en évidence plusieurs interactions centrées autour d’EGFR, apparaissant comme un driver de prolifération cérébrale malgré l’exclusion des mutations activatrices. Par ailleurs, le risque de progression cérébrale était réduit dans le bras traité par pemetrexed. Le taux le plus élevé de progression cérébrale était observé dans le bras traité par durvalumab. Ce travail a identifié une signature de 24 gènes spécifique des cancers bronchiques avec MC. De futures études seront nécessaires pour préciser les implications fonctionnelles de ces gènes et mieux comprendre le processus métastatique cérébral dans l’objectif d’identifier, à partir de cette signature, de nouvelles cibles thérapeutiques pour la prise en charge des cancers bronchiques avec MC.

Introduction. - Concerns about the proper schedule for discontinuing immunotherapy have been raised by many clinicians, as well as the minimal check-up required to assess residual disease before stopping immunotherapy. In fact, there currently exist no recommendations concerning immunotherapy prescription and optimal assessment in the event of persistent oncological response in cases of metastatic non-small cell lung cancer (NSCLC).Methods. - We conducted an online survey among board-certified French Thoracic Oncologists belonging to two professional associations. The survey included multiple-choice questions that either stood alone or were included in case reports. Results. - The survey was sent to 490 physicians, of whom 88 responded. For minimal residual disease assessment after 2 years of immunotherapy, PET-scan is prescribed by 92% of respon-dents and cerebral MRI by 59%. In the event of complete response after 2 years of treatment, 83% of physicians stop prescribing pembrolizumab and 70% discontinue nivolumab. In the event of partial response, 88% of respondents continue immunotherapy. In this case, only 33% use a complementary locoregional treatment such as radiotherapy.Conclusion. - Our survey highlights a pronounced tendency to stop immunotherapy in the event of complete oncological response. In the event of partial morphologic response, on the other hand, there is a tendency to continue immunotherapy. However, the use of locoregional treat-ments remains more heterogeneous.(c) 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.

The study aimed to assess the cost-effectiveness in France of atezolizumab monotherapy as adjuvant treatment following resection and platinum-based chemotherapy for patients with stage II-IIIA non-small cell lung cancer (NSCLC) with PD-L1≥50% of tumour cells vs best supportive care (BSC), excluding EGFR and ALK+.

Abstract Purpose: Targeted therapies (TT) and immune checkpoint blockers (ICB) have revolutionized the approach to non–small cell lung cancer (NSCLC) treatment in the era of precision medicine. Their impact as switch maintenance therapy based on molecular characterization is unknown. Patients and Methods: SAFIR02-Lung/IFCT 1301 was an open-label, randomized, phase II trial, involving 33 centers in France. We investigated eight TT (substudy-1) and one ICB (substudy-2), compared with standard-of-care as a maintenance strategy in patients with advanced EGFR, ALK wild-type (wt) NSCLC without progression after first-line chemotherapy, based on high-throughput genome analysis. The primary outcome was progression-free survival (PFS). Results: Among the 175 patients randomized in substudy-1, 116 received TT (selumetinib, vistusertib, capivasertib, AZD4547, AZD8931, vandetanib, olaparib, savolitinib) and 59 standard-of-care. Median PFS was 2.7 months [95% confidence interval (CI), 1.6–2.9] with TT versus 2.7 months (1.6–4.1) with standard-of-care (HR, 0.97; 95% CI, 0.7–1.36; P = 0.87). There were no significant differences in PFS within any molecular subgroup. In substudy-2, 183 patients were randomized, 121 received durvalumab and 62 standard-of-care. Median PFS was 3.0 months (2.3–4.4) with durvalumab versus 3.0 months (2.0–5.1) with standard-of-care (HR, 0.86; 95% CI, 0.62–1.20; P = 0.38). Preplanned subgroup analysis showed an enhanced benefit with durvalumab in patients with PD-L1 tumor proportion score (TPS) ≥1%, (n = 29; HR, 0.29; 95% CI, 0.11–0.75) as compared with PD-L1 <1% (n = 31; HR, 0.71; 95% CI, 0.31–1.60; Pinteraction = 0.036). Conclusions: Molecular profiling can feasibly be implemented to guide treatment choice for the maintenance strategy in EGFR/ALK wt NSCLC; in this study it did not lead to substantial treatment benefits beyond durvalumab for PD-L1 ≥ 1 patients.