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 - PubMed (original) (raw)
Clinical Trial
. 2019 Mar 1;37(7):537-546.
doi: 10.1200/JCO.18.00149. Epub 2019 Jan 8.
Delvys Rodríguez-Abreu 2, Andrew G Robinson 3, Rina Hui 4, Tibor Csőszi 5, Andrea Fülöp 6, Maya Gottfried 7, Nir Peled 8, Ali Tafreshi 9, Sinead Cuffe 10, Mary O'Brien 11, Suman Rao 12, Katsuyuki Hotta 13, Kristel Vandormael 14, Antonio Riccio 15, Jing Yang 15, M Catherine Pietanza 15, Julie R Brahmer 16
Affiliations
- PMID: 30620668
- DOI: 10.1200/JCO.18.00149
Clinical Trial
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
Martin Reck et al. J Clin Oncol. 2019.
Abstract
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.
Comment in
- Does Platinum-Based Chemotherapy Still Have a Role in First-Line Treatment of Advanced Non-Small-Cell Lung Cancer?
Lisberg A, Garon EB. Lisberg A, et al. J Clin Oncol. 2019 Mar 1;37(7):529-536. doi: 10.1200/JCO.18.01534. Epub 2019 Jan 24. J Clin Oncol. 2019. PMID: 30676857 No abstract available. - Extended follow-up on KEYNOTE-024 suggests significant survival benefit for pembrolizumab in patients with PD-L1 ≥50%, but unanswered questions remain.
Pacheco JM, Gao D, Camidge DR. Pacheco JM, et al. Ann Transl Med. 2019 Jul;7(Suppl 3):S127. doi: 10.21037/atm.2019.05.72. Ann Transl Med. 2019. PMID: 31576334 Free PMC article. No abstract available. - Pembrolizumab monotherapy for PD-L1 ≥50% non-small cell lung cancer, undisputed first choice?
Theelen WSME, Baas P. Theelen WSME, et al. Ann Transl Med. 2019 Jul;7(Suppl 3):S140. doi: 10.21037/atm.2019.06.35. Ann Transl Med. 2019. PMID: 31576347 Free PMC article. No abstract available. - Can PD-L1 tumor proportion score be used as the key to unlocking the KEYNOTE studies of pembrolizumab in advanced lung cancer?
Piper AJ, Sehgal K, Costa DB, Rangachari D. Piper AJ, et al. Transl Lung Cancer Res. 2019 Oct;8(5):715-722. doi: 10.21037/tlcr.2019.05.12. Transl Lung Cancer Res. 2019. PMID: 31737509 Free PMC article. No abstract available. - First-line immunotherapy for patients with advanced stage or metastatic non-small cell lung cancer…finally what threshold of PD-L1 expression on tumor cells?
Hofman P. Hofman P. Transl Lung Cancer Res. 2019 Oct;8(5):728-730. doi: 10.21037/tlcr.2019.04.18. Transl Lung Cancer Res. 2019. PMID: 31737511 Free PMC article. No abstract available. - The KEY to the end of the chemotherapy in advanced non-small cell lung cancer, or not yet?
Huang Y, Walsh RJ, Soo RA. Huang Y, et al. Transl Lung Cancer Res. 2019 Oct;8(5):731-737. doi: 10.21037/tlcr.2019.04.17. Transl Lung Cancer Res. 2019. PMID: 31737512 Free PMC article. No abstract available.
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