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Outside clinical trials, few data are available on the effect of long-term first-line pembrolizumab in patients with advanced non–small-cell lung cancers with ≥50% of tumor cells expressing programmed cell death ligand 1 (PD-L1). This French, multicenter study included consecutive advanced patients with non–small-cell lung cancer given first-line pembrolizumab alone between May 2017 (authorization date for this indication) and November 2019 (authorization date for pembrolizumab–chemotherapy combination). Information was collected from patients’ medical files, with a local evaluation of the response and progression-free survival (PFS). Overall survival (OS) was calculated from pembrolizumab onset using the Kaplan-Meier method. The analysis concerned 845 patients, managed in 33 centers: median age: 65 (range: 59–72) years, 67.8% men, 78.1% Eastern Cooperative Oncology Group performance status 0/1, 38.9%/51.5%/6.6% active, ex or never-smokers, respectively, 10.9%/16.8% taking or recently took corticosteroids/antibiotics, 69.6% nonsquamous histology, 48.9% ≥75% PD-L1–positive, and 20.8% had brain metastases at diagnosis. After a median (95% CI) follow-up of 45 (44.1–45.9) months, respective median (95% CI) PFS and OS lasted 8.2 (6.9–9.2) and 22 (8.5–25.9) months; 3-year PFS and OS rates were 25.4% and 39.4%, respectively. Multivariate analysis retained never-smoker status, adenocarcinoma histology, Eastern Cooperative Oncology Group performance status ≥2, and neutrophil/lymphocyte ratio >4 as being significantly associated with shorter survival, but not brain metastases at diagnosis or <75% PD-L1 tumor-cell expression. These long-term results of pembrolizumab efficacy based on a nationwide “real-world” cohort reproduced those obtained in clinical trials.

Pleural mesothelioma usually presents at an advanced, incurable stage. Chemotherapy with platinum–pemetrexed is a standard treatment. We hypothesised that the addition of pembrolizumab to platinum–pemetrexed would improve overall survival in patients with pleural mesothelioma.

DLL3, an atypical Notch ligand, is expressed in SCLC tumors but is not detectable in normal adult tissues. Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate containing a DLL3-targeting antibody tethered to a cytotoxic agent pyrrolobenzodiazepine by means of a protease-cleavable linker. The efficacy and safety of Rova-T compared with topotecan as second-line therapy in patients with SCLC expressing high levels of DLL3 (DLL3-high) was evaluated.

This open-label, phase 1–2 study evaluated the safety and efficacy of rovalpituzumab tesirine (Rova-T), an antibody-drug conjugate targeting DLL3, plus immune checkpoint inhibitors nivolumab plus or minus ipilimumab in previously treated extensive-stage SCLC (ES SCLC).

Approved systemic treatments for malignant pleural mesothelioma (MPM) have been limited to chemotherapy regimens that have moderate survival benefit with poor outcomes. Nivolumab plus ipilimumab has shown clinical benefit in other tumour types, including first-line non-small-cell lung cancer. We hypothesised that this regimen would improve overall survival in MPM.

L’immunothérapie par inhibiteurs de points de contrôle immunitaires (ICI) a récemment révolutionné la prise en charge de nombreux cancers solides. Les ICI ont pour but de restaurer l’action du lymphocyte T sur la cellule tumorale en inhibant des signaux de régulation négative impliqués dans la cancérogenèse. L’utilisation en routine des ICI depuis quelques années a permis d’en identifier le profil de tolérance. Les effets secondaires sont immuno-médiés, secondaires à la stimulation du système immunitaire induite par le traitement. Ces effets secondaires restent rares en comparaison avec ceux observés avec les chimiothérapies standards mais sont potentiellement graves, et peuvent remettre en cause la poursuite d’un traitement efficace. De nombreuses nouvelles immunothérapies sont en cours de développement, dont les mécanismes d’action sont variés, mais toujours dans le but de restaurer la réponse immunitaire anti-tumorale. De nouvelles molécules impliquent de nouveaux profils de tolérance, d’autant plus qu’un grand nombre d’essais cliniques évaluent des associations d’immunothérapies. Étant donné la multitude de traitements à l’étude, la connaissance et la prise en charge de ces toxicités sera un enjeu majeur dans le choix des nouvelles séquences thérapeutiques de nombreuses pathologies tumorales. En effet, malgré le pronostic sombre des types tumoraux concernés par ces innovations, l’amélioration progressive des données de survie dans ces pathologies entraîne une exposition au traitement de plus en plus longue. La tolérance et la qualité de vie pendant le traitement deviennent donc des arguments majeurs de la décision thérapeutique.

Lung cancer screening with low-dose chest CT (LDCT) reduces the mortality of eligible individuals. Blood signatures might act as a standalone screening tool, refine the selection of patients at risk, or help to classify undetermined nodules detected on LDCT. We previously showed that circulating tumour cells (CTCs) could be detected, using the isolation by size of epithelial tumour cell technique (ISET), long before the cancer was diagnosed radiologically. We aimed to test whether CTCs could be used as a biomarker for lung cancer screening.

Improved outcome has been shown in patients with synchronous oligometastatic (sOM) NSCLC when treated with radical intent. As a uniform definition of sOM NSCLC is lacking, we developed a definition and diagnostic criteria by a consensus process.

KRASmutation is the most frequent molecular alteration found in advanced NSCLC; it is associated with a poor prognosis without available targeted therapy. Treatment options for NSCLC have been recently enriched by the development of immune checkpoint inhibitors (ICIs), and data about its efficacy in patients with KRAS-mutant NSCLC are discordant. This study assessed the routine efficacy of ICIs in advanced KRAS-mutant NSCLC.

This randomized phase II trial aimed at evaluating the engineered programmed cell death ligand 1 (PD-L1) antibody atezolizumab in SCLC progressing after first-line platinum–etoposide chemotherapy.

Thymic epithelial tumors (TETs) are rare malignancies that may be aggressive and difficult to treat. In the advanced setting, systemic treatments may be delivered as primary therapy before surgery or definitive radiotherapy, as exclusive treatment when no focal treatment is feasible, or in the setting of recurrences. Réseau tumeurs THYMIques et Cancer (RYTHMIC) is the nationwide network for TETs in France. The objective of the study was to describe the modalities and analyze the efficacy of systemic treatments for patients with advanced TETs included in the RYTHMIC prospective database hosted by the French Thoracic Cancer Intergroup.

L’accès au dépistage du cancer en France a été facilité par la mise en place de programmes organisés (cancer du sein et cancer colorectal) et de recommandations nationales (cancer du col de l’utérus). Des arbitrages personnels peuvent également motiver la participation au dépistage du cancer de la prostate. Cet article présente une analyse des comportements de la population générale française sur plus de 10 ans face au dépistage du cancer et de la perception de cette démarche par les médecins généralistes. On peut ainsi noter que si le dépistage du cancer du sein est établi de manière stable et relativement homogène dans la population, d’autres, comme celui du cancer colorectal et de la prostate sont sous une dépendance plus forte de facteurs sociologiques et de la précarité. Le monitoring de l’adhésion est ainsi d’autant plus important que la participation pourrait être affectée par l’impact des conditions sociales et de la précarité dans un contexte de crise économique.

Malignant pleural mesothelioma is an aggressive cancer with poor prognosis, linked to occupational asbestos exposure. Vascular endothelial growth factor is a key mitogen for malignant pleural mesothelioma cells, therefore targeting of vascular endothelial growth factor might prove effective. We aimed to assess the effect on survival of bevacizumab when added to the present standard of care, cisplatin plus pemetrexed, as first-line treatment of advanced malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) grows aggressively within the thoracic cavity and has a very low cure rate, thus highlighting the need for identification of new therapeutic targets. Adrenomedullin (AM) is a multifunctional peptide that is highly expressed in several tumors and plays an important role in angiogenesis and tumor growth after binding to its receptors, calcitonin receptor–like receptor/receptor activity–modifying protein 2 (CLR/RAMP2) and calcitonin receptor–like receptor/receptor activity–modifying protein 3 (CLR/RAMP3).

Introduction:Targeting the EGFR pathway is a rational approach to treat patients with advanced NSCLC. Necitumumab, a second-generation recombinant fully human immunoglobulin G1 monoclonal antibody directed against EGFR, has recently been assessed in combination with first-line cisplatin-based chemotherapy.Areas covered:This article reviews literature on necitumumab development, from preclinical data to results of Phase III clinical trials, either published or presented in international scientific conferences. Ongoing clinical trials were searched with the clinical-trials.gov website.Expert opinion:During the last decade, advances in treatment of metastatic NSCLC have been exclusively achieved in patients with non-squamous histology. In this context, any treatment improvement, even modest, was eagerly awaited for patients with squamous NSCLC. In this patient’s population, the SQUIRE Phase III study demonstrated a relatively small, but statistically significant survival benefit in patients treated with necitumumab in combination with standard chemotherapy (cisplatin and gemcitabin) compared with those treated with chemotherapy alone. However, the identification of predictive biomarker for treatment outcome is still needed to select the patients who will experience a large benefit from the targeted treatment.

La stratégie thérapeutique du cancer bronchique s'oriente de plus en plus vers l'individualisation des traitements, notamment avec l'avènement de thérapies bioguidées. Afin de permettre l'accès de tous les malades à ces traitements, l'INCa a labellisé en 2006 un réseau de 28 plateformes de biologie réparties sur tout le territoire français. Le développement de ces plateformes a été rendu possible grâce à un financement public. L'INCa recommande à ce jour l'analyse de sept biomarqueurs pour tout patient atteint de cancer bronchique non à petites cellules non épidermoïde métastatique ou inéligible à un traitement local. Pour des raisons techniques et financières, il convient de respecter ce cadre. Néanmoins, idéalement, il faudrait pouvoir élargir la réalisation d'une cartographie moléculaire à tous les stades et tous les types histologiques afin, d'une part, d'améliorer nos connaissances en termes de biologie du cancer bronchique et, d'autre part, de permettre à tous les patients l'accès à une stratégie thérapeutique bioguidée.

Previous pleural endoscopy is considered to be a relative contraindication to further medical thoracoscopy. We reviewed our experience in patients undergoing more than one thoracoscopy irrespective of the primary indication. From January 2001 to December 2006, patient baseline characteristics, endoscopic appearance and technique, volume of pleural fluid and final histological diagnosis were collated in all patients undergoing more than one thoracoscopy. The endpoints were morbidity and mortality related to the procedures, to compare the length of procedure time between pleural endoscopies in individual patients and the degree of difficulty of the second or subsequent thoracoscopic procedure. During this period, 29 patients underwent 'redo' thoracoscopy resulting in a total of 61 procedures (rate of 'redo' thoracoscopy; 9.1%). The mean time between thoracoscopies was 5.3+/-3.8 months. Although pleural adhesions were more common at the time of the subsequent procedure, it did not result in failure to induce a pneumothorax or perform the procedure. There was no difference in the duration of procedure between the primary and subsequent thoracoscopy (P=0.46), as well as no complications directly attributed to the repeat pleural endoscopy. Repeat medical thoracoscopy is technically feasible in patients with pleural disease without an associated increased morbidity and mortality.

Pulmonary function tests are used to select patients with non–small-cell lung cancer (NSCLC) suitable for thoracic surgery. We studied the impact of pulmonary function tests on both quantitative (morbidity, mortality, and overall survival [OS]) and qualitative (quality of life [QOL]) outcomes of patients undergoing thoracic surgery for NSCLC.

Patients with advanced-stage non-small cell lung cancer (NSCLC) whose tumors harbor an anaplastic lymphoma kinase (ALK) gene rearrangement benefit from treatment with multiple ALK inhibitors (ALKi). Approximately 30% of tumor biopsies contain insufficient tissue for successful ALKmolecular characterization. This study evaluated the added value of analyzing circulating tumor cells (CTCs) as a surrogate to ALKtissue analysis and as a function of the response to ALKi.