Dynamics of the 12C-12C System in the Static Molecular Mean Field Approximation

peer reviewe

Venous thrombotic events and impact on outcomes in patients treated with first-line single-agent pembrolizumab in PD-L1 ≥ 50% advanced non small cell lung cancer

International audienceBackgroundFew data are available on the impact of venous thrombotic events (VTE) in patients with metastatic non-small cell lung cancer (mNSCLC) treated with immunotherapy.MethodsThis is a secondary analysis of the ESKEYP study, a national, retrospective, multicenter study that consecutively included all PD-L1 ≥ 50% mNSCLC patients who initiated first-line treatment with pembrolizumab monotherapy. From May 2017 to November 2019, 845 patients were included (from availability of pembrolizumab in this indication in France to the authorization of the combination with chemotherapy). Impact of VTE and patient characteristics were analyzed.ResultsOf the 748 patients (88.5%) with available data, the incidence of VTE was 14.8% (111/748). At pembrolizumab initiation, Khorana score was ≥ 2 for 55.0% (61/111) of them. Recurrence of VTE was reported for 4 of the 111 patients and 5 had bleeding complications. Patients with VTE were significantly younger, had more frequently long-term corticosteroids treatment and more often liver metastases. Progression-free survival (PFS) was significantly shorter in patients with VTE compared to patients without VTE: 6.1 (95% CI 4.1–9.0) months vs. 8.3 (6.9–10.3) months (p = 0.03). VTE did not significantly impact overall survival (OS): 15.2 (10.0–24.7) months with VTE and 22.6 (18.4–29.8) months without VTE (p = 0.07). In multivariate analysis for PFS and OS, HRs for VTE were 1.3 (0.99–1.71), p = 0.06 and 1.32 (0.99–1.76), p = 0.05.ConclusionThe incidence of VTE appears to be as high with in first-line immunotherapy as with chemotherapy in patients with mNSCLC, with in patient with VTE, a no significant trend for lower PFS and OS in multivariate analysis. more marked impact on PFS than on OS

Three-Year Overall Survival of Patients With Advanced Non–Small-Cell Lung Cancers With ≥50% PD-L1 Expression Treated With First-Line Pembrolizumab Monotherapy in a Real-World Setting (ESCKEYP GFPC Study)

International audienceOutside 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