Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma

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

Background: 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. Objective: 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]). Design, setting, and participants: Patients were cisplatin ineligible, had treatmentnaive, 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 65 yr (n = 302), 75 yr (n = 179), 65 yr with ECOG PS2 (65 yr + ECOG PS2; n = 119), and 75 yr + ECOG PS2 (n = 78). Intervention: All patients received pembrolizumab 200 mg intravenously every 3 wk until confirmed progression, intolerable toxicity, patient withdrawal, or 24 mo of therapy. Outcome measurements and statistical analysis: 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. Results and limitations: ORRs for the 65 yr, 75 yr, 65 yr + 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 65 yr and 65 yr + 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