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.
By M. Reck, D. Rodríguez-Abreu, A. Robinson, R. Hui, T. Csőszi, A. Fülöp, M. Gottfried, N. Peled, A. Tafreshi, S. Cuffe and 8 more. Journal of Clinical Oncology, 2019
1,408 citations recorded by the source corpus.
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.
Subfields: Oncology, Pulmonary and Respiratory Medicine, Radiology, Nuclear Medicine and Imaging
View Paper: https://www.semanticscholar.org/paper/6fe8d9f862c5f8cca901e7a8293c74a00410315e
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Citations in the corpus
- Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non–Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50% (2021, methodology): “1, Eastern Cooperative Oncology Group performance status of 0 or 1, and life expectancy of at least 3 months.(4,10) Patients with sensitizing EGFR or ALK alterations, untreated brain metastases, or active autoimmune disease requiring systemic treatment or receiving systemic glucocorticoids or immuno”
- Five-Year Overall Survival for Patients With Advanced Non‒Small-Cell Lung Cancer Treated With Pembrolizumab: Results From the Phase I KEYNOTE-001 Study (2019, result): “2 months).(22) Data from randomized trials have thus shown data that are similar to that of the single-arm KEYNOTE-001 study at analogous time points and suggest that patients with PD-L1 TPS of 50% or greater may derive greater absolute benefit from pembrolizumab as a first-line therapy than as a se”
- Immune Checkpoint Inhibitors in Cancer Therapy (2022, background): “Accordingly, several studies have exhibited that combination therapy with ICIs plus other therapeutic approaches, such as chemotherapy [86], radiotherapy, cancer vaccines, and also CXCR4 blockade therapy [87] can efficiently circumvent tumour resistance to ICI therapy.”