As reported in the Journal of Clinical Oncology by Vuky et al, 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) ≥ 10 or lymph node–only metastasis.
Study Details
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 CPS ≥ 10. Response was assessed by independent central review using Response Evaluation Criteria in Solid Tumors version 1.1.
“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.”— Vuky et al
Tweet this quote
Key Findings
At data cutoff, 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–not reached); responses lasted ≥ 12 and ≥ 24 months in 67% and 52% of responders. 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 CPS ≥ 10 vs 251 patients with CPS < 10, objective response rates were 47.3% vs 20.3% and median durations of response were not reached (95% CI = 18.1 months–not reached) vs 18.2 months (95% CI = 9.7 months–not reached), with 57.0% vs 45.0% 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 47.0% vs 24.0%.
Among 51 patients with lymph node–only metastasis vs 315 with visceral metastasis, objective response rates were 49.0% vs 25.1% and median overall survival was 27.0 months (95% CI = 12.4 months–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.”
Jacqueline Vuky, MD, of Oregon Health & Science University, Portland, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Merck Sharp & Dohme Corp, a subsidiary of Merck & Co. For full disclosures of the study authors, visit ascopubs.org.
