Long-Term Outcomes in KEYNOTE-052: Phase II Study Investigating First-Line Pembrolizumab in Cisplatin-Ineligible Patients With Locally Advanced or Metastatic Urothelial Cancer.

Autor:	Vuky J; Oregon Health & Science University, Portland, OR., Balar AV; Perlmutter Cancer Center, NYU Langone Health, New York, NY., Castellano D; Hospital Universitario 12 de Octubre, Madrid, Spain., O'Donnell PH; The University of Chicago, Chicago, IL., Grivas P; Cleveland Clinic, Cleveland OH., Bellmunt J; Beth Israel Deaconess Medical Center/IMIM research Institute, Harvard Medical School, Boston, MA., Powles T; Barts Cancer Institute, Queen Mary University of London, London, United Kingdom., Bajorin D; Memorial Sloan Kettering Cancer Center, New York, NY., Hahn NM; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD., Savage MJ; Merck & Co., Kenilworth, NJ., Fang X; Merck & Co., Kenilworth, NJ., Godwin JL; Merck & Co., Kenilworth, NJ., Frenkl TL; Merck & Co., Kenilworth, NJ., Homet Moreno B; Merck & Co., Kenilworth, NJ., de Wit R; Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Plimack ER; Fox Chase Cancer Center, Philadelphia, PA.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2020 Aug 10; Vol. 38 (23), pp. 2658-2666. Date of Electronic Publication: 2020 Jun 17.
DOI:	10.1200/JCO.19.01213
Abstrakt:	Purpose: The phase II single-arm KEYNOTE-052 study evaluated the efficacy and safety of first-line pembrolizumab for patients with locally advanced or metastatic cisplatin-ineligible urothelial carcinoma (UC). Patients and Methods: Three hundred seventy patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 24 months. Positive tumor programmed death ligand 1 (PD-L1) expression was defined as combined positive score (CPS) ≥ 10. Response was assessed by independent central review every 9 weeks per RECIST v1.1. The primary end point was objective response rate (ORR). Results: At data cutoff (September 26, 2018), the minimum follow-up was 2 years since the last patient enrolled. ORR was 28.6% (95% CI, 24.1% to 33.5%); 33 patients (8.9%) and 73 patients (19.7%) achieved complete and partial response, respectively. The median duration of response was 30.1 months (95% CI, 18.1 months to not reached [NR]); responses lasted ≥ 12 and ≥ 24 months in 67% and 52% of patients, respectively. Forty patients with complete or partial response completed 2 years of study treatment, and 32 had ongoing response at completion. Median overall survival (OS) was 11.3 months (95% CI, 9.7 to 13.1 months), and 12- and 24-month OS rates were 46.9% and 31.2%, respectively. In patients with CPS ≥ 10, ORR was 47.3% (95% CI, 37.7% to 57.0%) and median OS was 18.5 months (95% CI, 12.2 to 28.5 months). In patients with lymph node-only disease, ORR was 49.0% (95% CI, 34.8% to 63.4%), and median OS was 27.0 months (12.4 months to NR). There were no new safety signals. Conclusion: First-line pembrolizumab confers meaningful and durable clinical response in cisplatin-ineligible patients with advanced UC and is associated with prolonged OS, particularly with PD-L1 CPS ≥ 10 and lymph node-only disease.
Databáze:	MEDLINE
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