scholarly journals Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non–Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater

2019 ◽  
Vol 37 (7) ◽  
pp. 537-546 ◽  
Author(s):  
Martin Reck ◽  
Delvys Rodríguez–Abreu ◽  
Andrew G. Robinson ◽  
Rina Hui ◽  
Tibor Csőszi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Failure Time ◽  
Progression Free Survival ◽  
Small Cell ◽  
Structural Failure ◽  
Small Cell Lung ◽  
Free Survival ◽  
Inverse Probability ◽  
Platinum Based Chemotherapy

Purpose In the randomized, open-label, phase III KEYNOTE-024 study, pembrolizumab significantly improved progression-free survival and overall survival (OS) compared with platinum-based chemotherapy in patients with previously untreated advanced non–small-cell lung cancer (NSCLC) with a programmed death ligand 1 tumor proportion score of 50% or greater and without EGFR/ALK aberrations. We report an updated OS and tolerability analysis, including analyses adjusting for potential bias introduced by crossover from chemotherapy to pembrolizumab. Patients and Methods Patients were randomly assigned to pembrolizumab 200 mg every 3 weeks (for up to 2 years) or investigator’s choice of platinum-based chemotherapy (four to six cycles). Patients assigned to chemotherapy could cross over to pembrolizumab upon meeting eligibility criteria. The primary end point was progression-free survival; OS was an important key secondary end point. Crossover adjustment analysis was done using the following three methods: simplified two-stage method, rank-preserving structural failure time, and inverse probability of censoring weighting. Results Three hundred five patients were randomly assigned (pembrolizumab, n = 154; chemotherapy, n = 151). At data cutoff (July 10, 2017; median follow-up, 25.2 months), 73 patients in the pembrolizumab arm and 96 in the chemotherapy arm had died. Median OS was 30.0 months (95% CI, 18.3 months to not reached) with pembrolizumab and 14.2 months (95% CI, 9.8 to 19.0 months) with chemotherapy (hazard ratio, 0.63; 95% CI, 0.47 to 0.86). Eighty-two patients assigned to chemotherapy crossed over on study to receive pembrolizumab. When adjusted for crossover using the two-stage method, the hazard ratio for OS for pembrolizumab versus chemotherapy was 0.49 (95% CI, 0.34 to 0.69); results using rank-preserving structural failure time and inverse probability of censoring weighting were similar. Treatment-related grade 3 to 5 adverse events were less frequent with pembrolizumab compared with chemotherapy (31.2% v 53.3%, respectively). Conclusion With prolonged follow-up, first-line pembrolizumab monotherapy continues to demonstrate an OS benefit over chemotherapy in patients with previously untreated, advanced NSCLC without EGFR/ALK aberrations, despite crossover from the control arm to pembrolizumab as subsequent therapy.

scholarly journals Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non–Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50%

2021 ◽  
pp. JCO.21.00174
Author(s):  
Martin Reck ◽  
Delvys Rodríguez-Abreu ◽  
Andrew G. Robinson ◽  
Rina Hui ◽  
Tibor Csőszi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Free Survival ◽  
Chemotherapy Group ◽  
Platinum Based Chemotherapy

PURPOSE We report the first 5-year follow-up of any first-line phase III immunotherapy trial for non–small-cell lung cancer (NSCLC). KEYNOTE-024 (ClinicalTrials.gov identifier: NCT02142738 ) is an open-label, randomized controlled trial of pembrolizumab compared with platinum-based chemotherapy in patients with previously untreated NSCLC with a programmed death ligand-1 (PD-L1) tumor proportion score of at least 50% and no sensitizing EGFR or ALK alterations. Previous analyses showed pembrolizumab significantly improved progression-free survival and overall survival (OS). METHODS Eligible patients were randomly assigned (1:1) to pembrolizumab (200 mg once every 3 weeks for up to 35 cycles) or platinum-based chemotherapy. Patients in the chemotherapy group with progressive disease could cross over to pembrolizumab. The primary end point was progression-free survival; OS was a secondary end point. RESULTS Three hundred five patients were randomly assigned: 154 to pembrolizumab and 151 to chemotherapy. Median (range) time from randomization to data cutoff (June 1, 2020) was 59.9 (55.1-68.4) months. Among patients initially assigned to chemotherapy, 99 received subsequent anti–PD-1 or PD-L1 therapy, representing a 66.0% effective crossover rate. Median OS was 26.3 months (95% CI, 18.3-40.4) for pembrolizumab and 13.4 months (9.4-18.3) for chemotherapy (hazard ratio, 0.62; 95% CI, 0.48-0.81). Kaplan-Meier estimates of the 5-year OS rate were 31.9% for the pembrolizumab group and 16.3% for the chemotherapy group. Thirty-nine patients received 35 cycles (ie, approximately 2 years) of pembrolizumab, 82.1% of whom were still alive at data cutoff (approximately 5 years). Toxicity did not increase with longer treatment exposure. CONCLUSION Pembrolizumab provides a durable, clinically meaningful long-term OS benefit versus chemotherapy as first-line therapy for metastatic NSCLC with PD-L1 tumor proportion score of at least 50%.

scholarly journals CMET-01. IMMUNE CHECKPOINT INHIBITORS FOR NON-SMALL CELL LUNG CANCER WITH BRAIN METASTASIS: THE ROLE OF GAMMA KNIFE RADIOSURGERY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi51-vi51
Author(s):  
Min Ho Lee ◽  
Kyung-Rae Cho ◽  
Jung-Il Lee
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Gamma Knife Radiosurgery ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Group A

Abstract PURPOSE Immune checkpoint inhibitors (ICIs) are approved for the treatment of non-small cell lung cancer (NSCLC), but the safety and efficacy of the combined treatment with ICIs and gamma knife radiosurgery (GKS) remain undefined. METHODS We retrospectively reviewed the medical records of patients with brain metastases from NSCLC who were treated with ICIs between January 2015 and December 2017 at our institute. Of the 134 patients identified, 77 who were assessable for brain responses were categorized into three groups based on the medication administered and GKS: Group A, ICI alone; Group B, ICI with concurrent GKS within 14 days; and Group C, ICI with non-concurrent GKS. RESULTS The median follow-up duration after the diagnosis of brain metastases was 19.1 (range, 1–68.7) months. At the last follow-up, 48 patients (62.3%) died. The overall survival was shorter in Group A than in Groups B and C (P=0.001). There were no statistically significant differences in the intracranial disease progression-free survival (P=0.514), local progression-free survival (P=0.358), and complication rates among the three groups. Twelve patients presented with leptomeningeal seeding (LMS) during follow-up. There was a significant difference in the LMS-free duration from the time of administering ICIs (P=0.011) and the diagnosis of metastasis (P< 0.001). CONCLUSION GKS in combination with ICI showed no favorable overall survival outcome in the treatment of brain metastasis from NSCLC. However, GKS with ICI did not increase the risk of complications. Furthermore, compared with ICI alone, GKS with ICI may be associated with a reduced incidence of LMS.

Prognostic value of peripheral naive CD8+ T cells in oligometastatic non-small-cell lung cancer

2021 ◽  
Author(s):  
Xin Zhao ◽  
Yan Zhang ◽  
Zhenlin Gao ◽  
Yaguang Han
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
Immune Cells ◽  
Prognostic Value ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival

Aim: This study aimed to investigate the prognostic value of peripheral naive and memory CD8+ and CD4+ T cells and other immune cells in patients with oligometastatic non-small-cell lung cancer (NSCLC) undergoing radiotherapy (RT). Methods: A total of 142 patients with oligometastatic NSCLC treated with RT were enrolled, and their blood samples were collected within 3 days before RT. Immune cells were identified by flow cytometry. Results: Patients with high levels of naive CD8+ T cells had longer overall survival (p = 0.004) and progression-free survival (p = 0.001) than those with low levels of naive CD8+ T cells. Multivariate analyses revealed that naive CD8+ T cells were independently correlated with overall survival (p = 0.019) and progression-free survival (p = 0.024). Conclusion: The results suggest that peripheral naive CD8+ T cells may be an independent prognostic indicator for patients with oligometastatic NSCLC undergoing RT.

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