Pembrolizumab as First-line Therapy in Cisplatin-ineligible Advanced Urothelial Cancer (KEYNOTE-052): Outcomes in Older Patients by Age and Performance Status

Patients with treatment-naive advanced urothelial cancer (UC) ineligible for cisplatin-based chemotherapy are typically older and have comorbidities, representing a difficult-to-treat population. To evaluate the safety and antitumor activity of first-line pembrolizumab in subgroups of cisplatin-ineligible older patients (aged ≥65 and ≥75 yr) with advanced UC in KEYNOTE-052 (NCT02335424), including those with poor performance status (Eastern Cooperative Oncology Group performance status score 2 [ECOG PS2]). Patients were cisplatin ineligible, had treatment-naive, histologically/cytologically confirmed, locally advanced/metastatic UC with measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1]), and had ECOG PS0–2. Patient subgroups analyzed were aged ≥65yr (n = 302), ≥75 yr (n = 179), ≥65yr with ECOG PS2 (≥65yr+ECOG PS2; n = 119), and ≥75 yr+ECOG PS2 (n = 78). All patients received pembrolizumab 200mg intravenously every 3 wk until confirmed progression, intolerable toxicity, patient withdrawal, or 24 mo of therapy. The primary endpoint was objective response rate (ORR) as per RECIST v1.1. The key secondary endpoints were overall survival (OS), duration of response (DOR), and safety. ORRs for the ≥65yr, ≥75 yr, ≥65yr+ECOG PS2, and ≥75 yr+ECOG PS2 subgroups were 29%, 27%, 29%, and 31%, respectively; rates of complete and partial responses were similar across subgroups (9%, 5%, 6%, and 6%, and 20%, 22%, 23%, and 24%, respectively). Median DOR and OS were also consistent across the ≥65yr and ≥65yr+ECOG PS2 subgroups and the ≥75 yr and ≥75 yr+ECOG PS2 subgroups. Study limitations included open-label design, lack of a comparator group, and nature of post hoc exploratory analysis. The clinical benefit of pembrolizumab in advanced UC appeared to be consistent regardless of age and/or poor performance status. This study looked at whether older age and poorer performance status affect how well patients with previously untreated advanced urothelial cancer ineligible for standard-of-care treatment respond to pembrolizumab. Outcomes with pembrolizumab were not affected by older age or poorer performance status, making it an effective option. Pembrolizumab is effective and well tolerated in cisplatin-ineligible senior patients with advanced urothelial cancer, including those with poor performance status. Tumor response and outcomes were not impacted by poor performance status and/or older age.