KEYNOTE-361: Complete Response Outcomes With First-line Pembrolizumab or Platinum-Based Chemotherapy

In the randomized, open-label, phase 3 KEYNOTE-361 study, first-line pembrolizumab plus chemotherapy did not demonstrate superior efficacy against chemotherapy alone in patients with advanced urothelial carcinoma (aUC). Survival outcomes seemed similar in pembrolizumab monotherapy versus chemotherapy.

A post hoc exploratory analysis by Ozgur Ozyilkan and colleagues examined efficacy outcomes in patients who experienced complete response (CR) to pembrolizumab or chemotherapy during the KEYNOTE-361 trial. Results of the analysis will be presented at the American Society of Clinical Oncology 2023 Annual Meeting.

During the trial, patients with aUC were randomized 1:1:1 to receive either first-line pembrolizumab (200 mg IV every 3 weeks for up to 2 years) with or without chemotherapy (1000 mg/m² gemcitabine on day 1 and day 8 with investigator’s choice of cisplatin [70 mg/m²] or carboplatin [area under the concentration curve of 5 mg/mL/min] on day 1 of each 3-week cycle) or chemotherapy alone.

The end points of the post hoc analysis were duration of response and progression-free survival (PFS), as measured by a blinded independent central review using Response Evaluation Criteria in Solid Tumours v1.1 criteria, and overall survival (OS) in patients who achieved CR in the pembrolizumab monotherapy or chemotherapy arms.

A total of 37 (11.1%) of 307 patients in the pembrolizumab arm and 43 (12.2%) of 352 patients in the chemotherapy arm achieved CR. The median follow-up for patients who had CR was 30.7 months. Median PFS was not reached (NR; 95% CI, 30.3-NR) with pembrolizumab and 15.1 months (95% CI, 8.8-NR) with chemotherapy (hazard ratio [HR], 0.32; 95% CI, 0.15-0.70). The estimated 24-month PFS rates were 75.5% and 42.2% in the pembrolizumab and chemotherapy arms, respectively.

The median OS was NR (95% CI, NR-NR) with pembrolizumab and NR (95% CI, 25.1-NR) with chemotherapy (HR, 0.20; 95% CI, 0.06-0.70). The estimated 24-month OS rates were 94.1% and 69.5% in the pembrolizumab and chemotherapy arms, respectively. A total of 9 patients (26.5%) in the pembrolizumab arm and 21 patients (48.8%) in the chemotherapy arm experienced disease progression after an initial CR. Among patients who achieved CR, 2 patients (5.9%) in the pembrolizumab arm and 22 patients (51.2%) in the chemotherapy arm received subsequent therapy.

The post hoc exploratory analysis demonstrated that complete responses with pembrolizumab were more durable than those experienced with chemotherapy in patients with aUC. Further investigation into patient selection is needed to determine which patients could benefit the most from first-line pembrolizumab.