[Potential therapeutic implication of focal adhesion kinase in small-cell lung cancer].

The molecular steps leading to small cell lung cancer (SCLC) development and progression are still poorly understood, resulting in the absence of targeted therapy and an extremely poor prognosis. Activation of Focal Adhesion Kinase (FAK) plays a key role in the invasive behavior of this cancer in vitro. Our hypothesis is that FAK could be a therapeutic target in SCLC. Our work aims to describe a mouse model to study the role of FAK and the antitumoral potential of its inhibition in SCLC in vivo

Molecular Alterations and Estimated Indoor Radon in NSCLC Patients from the French National Cancer Institute Registry: Radon France Study [OA09.06]

BACKGROUND : Radon is a radioactive gas, considered the leading cause of lung cancer in non-smokers. We assessed the correlation between the radon exposure areas in France and the molecular alterations nationally registered in non-small cell lung cancer (NSCLC) patients. [...

Immune checkpoint blockers in solid organ transplant recipients and cancer: the INNOVATED cohort

Background Patients with solid organ transplant (SOT) and solid tumors are usually excluded from clinical trials testing immune checkpoint blockers (ICB). As transplant rates are increasing, we aimed to evaluate ICB outcomes in this population, with a special focus on lung cancer. Methods We conducted a multicenter retrospective cohort study collecting real data of ICB use in patients with SOT and solid tumors. Clinical data and treatment outcomes were assessed by using retrospective medical chart reviews in every participating center. Study endpoints were: overall response rate (ORR), 6-month progression-free survival (PFS), and grade ≥3 immune-related adverse events. Results From August 2016 to October 2022, 31 patients with SOT (98% kidney) and solid tumors were identified (36.0% lung cancer, 19.4% melanoma, 13.0% genitourinary cancer, 6.5% gastrointestinal cancer). Programmed death-ligand 1 expression was positive in 29% of tumors. Median age was 61 years, 69% were males, and 71% received ICB as first-line treatment. In the whole cohort the ORR was 45.2%, with a 6-month PFS of 56.8%. In the lung cancer cohort, the ORR was 45.5%, with a 6-month PFS of 32.7%, and median overall survival of 4.6 months. The grade 3 immune-related adverse events rate leading to ICB discontinuation was 12.9%. Allograft rejection rate was 25.8%, and risk of rejection was similar regardless of the type of ICB strategy (monotherapy or combination, 28% versus 33%, P = 1.0) or response to ICB treatment. Conclusions ICB could be considered a feasible option for SOT recipients with some advanced solid malignancies and no alternative therapeutic options. Due to the risk of allograft rejection, multidisciplinary teams should be involved before ICB therapy

Association of metastatic pattern and molecular status in metastatic lung non-small cell lung cancer adenocarcinomas

BACKGROUND : The recent identification of molecular alterations in some lung adenocarcinomas has led to the emergence of effective targeted therapies thus drastically improving their prognosis.The aim of our study was to investigate the association between driver oncogene alterations and metastatic patterns on imaging assessment, in a large cohort of metastatic lung adenocarcinoma patients. [...

OA07.06 Second Line Treatment Outcomes After Progression on Immunotherapy Plus Chemotherapy (IO-CT) In Advanced Non-small Cell Lung Cancer (aNSCLC)

INTRODUCTION : The combination of IO-CT has become the standard of care for patients with aNSCLC with a low or intermediate programmed death-ligand 1 (PD-L1) expression (<50%), and an option for patients with high PDL1 (≥50%) expression. There are no data available on the subsequent line (L2) outcomes after IO-CT. We aimed to assess the outcomes of various L2 treatments after IO-CT in aNSCLC. [...

Association of lung immune prognostic index (LIPI) with survival of first line immune checkpoint inhibitors single agent or in combination with chemotherapy in untreated advanced NSCLC patients

BACKGROUND : The Lung Immune Prognostic Index (LIPI), combining the derived neutrophils/[leucocytes minus neutrophils] ratio (dNLR) and lactate dehydrogenase (LDH), has been associated with survival for ICI-single agent in large cohorts of refractory advanced NSCLC. However the role of LIPI in untreated NSCLC patients has not been explored yet. We assessed the value of LIPI in the front-line setting of advanced NSCLC patients (pts) treated with ICI-single agent or in combination with chemotherapy and compared to a cohort of pts treated exclusively with chemotherapy (CT). [...

UNcommon EGFR mutations: International Case series on efficacy of osimertinib in Real-life practice in first liNe setting (UNICORN).

BACKGROUND About 10% of EGFR mutations (EGFRmut) are 'uncommon mutations' (ucEGFRmut). We aimed to collect real-world data about osimertinib for ucEGFRmut patients. METHODS This is a multi-center, retrospective study of ucEGFRmut (exon 20 insertions excluded) metastatic NSCLC osimertinib-treated as first EGFR inhibitor. RECIST and RANO-BM brain objective response rate (ORR) were evaluated by investigators. mPFS, mOS and mDOR were calculated from osimertinib initiation. Mutations found at resistance were collected. RESULTS 60 patients included (22 centres, 9 countries): median age - 64 years, 75% females, 83% Caucasian. The largest subgroups were G719X (30%), L861Q (20%) and de novo T790M (15%). ORR was 61%, mPFS 9.5 months (m), mDOR 17.4m, mOS 24.5m. Regarding patients with no concurrent common mutations or T790M (group A, n=44), ORR was 60%, mPFS 8.6 months, mDOR 11 months. For G719X ORR was 47%, mPFS 8.8m and mDOR 9.1m. For L861Q ORR was 80%, mPFS 16m and mDOR 16m. For de novo T790M ORR was 44%, mPFS 12.7m, mDOR 46.2m. Compound EGFRmut including common mutations had better outcome compared to only ucEGFRmut. For 13 patients with a RANO-BM evaluable brain metastases, brain ORR was 46%. For 14 patients, rebiopsy was analysed: 4 patients - additional EGFR mutation (C797S, D585Y, E709K), 3 - new TP53 mutation, 1 - c-Met amplification, 1 - PIK3CA mutation and 1 - neuroendocrine transformation. CONCLUSIONS Osimertinib demonstrated activity in ucEGFRmut with high rate of disease control systemically and intracranially. Several resistance mechanisms were identified. This report comprises, to the best of our knowledge, the largest dataset of its kind