As reported in the Journal of Clinical Oncology by Jacqueline Vuky, MD, of Oregon Health & Science University, Portland, and colleagues, long-term follow-up in the phase II KEYNOTE-052 study has shown durable responses with first-line pembrolizumab in cisplatin-ineligible locally advanced or metastatic urothelial cancer, with higher response rates and longer survival in patients with a PD-L1 combined positive score (CPS) of at least 10 or lymph node–only metastasis.1
Jacqueline Vuky, MD
In the study, 370 patients received pembrolizumab at 200 mg every 3 weeks for up to 24 months. Positive PD-L1 expression was defined as a CPS of at least 10. Response was assessed by independent central review using Response Evaluation Criteria in Solid Tumors, version 1.1.
At data cutoff, the minimum follow-up was 2 years since enrollment of the last patient. Among all patients, the objective response rate was 28.6%, with a median duration of response of 30.1 months (95% confidence interval [CI] = 18.1 months to not reached); responses lasted at least 12 and at least 24 months in 67% and 52% of responders, respectively. Of 40 responding patients completing 2 years of treatment, 32 had an ongoing response at completion. Median overall survival was 11.3 months (95% CI = 9.7–13.1 months), with 12- and 24-month rates of 46.9% and 31.2%.
Among 110 patients with a CPS of at least 10 vs 251 patients with a CPS up to 10, the objective response rates were 47.3% vs 20.3%, and the median duration of response was not reached (95% CI = 18.1 months to not reached) vs 18.2 months (95% CI = 9.7 months to not reached), with 57% vs 45% of responders having a response lasting 24 months or longer. Median overall survival was 18.5 months (95% CI = 12.2–28.5 months) vs 9.7 months (95% CI = 7.6–11.5 months), with a 24-month rate of 47% vs 24%.
“First-line pembrolizumab confers meaningful and durable clinical response in cisplatin-ineligible patients with advanced urothelial carcinoma and is associated with prolonged overall survival, particularly with PD-L1 CPS ≥ 10 and lymph node–only disease.”— Jacqueline Vuky, MD, and colleagues
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Among 51 patients with lymph node–only metastasis vs 315 with visceral metastasis, the objective response rates were 49.0% vs 25.1%, and the median overall survival was 27.0 months (95% CI = 12.4 months to not reached) vs 10.6 months (95% CI = 8.7–11.7 months). No new safety signals were identified.
The investigators concluded: “First-line pembrolizumab confers meaningful and durable clinical response in cisplatin-ineligible patients with advanced urothelial carcinoma and is associated with prolonged overall survival, particularly with PD-L1 CPS ≥ 10 and lymph node–only disease.”
Disclosure: Dr. Vuky has served in a consulting or advisory role for Seattle Genetics/Astellas; and has received institutional research funding from Roche/Genentech, Pharma, Celldex, Novartis, and Fortis Therapeutics.
1. Vuky J, Balar AV, Castellano D, et al: Long-term outcomes in KEYNOTE-052: Phase II study investigating first-line pembrolizumab in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer. J Clin Oncol. June 17, 2020 (early release online).