Opdivo offers 1st-line immuno-oncology option for metastatic urothelial cancer

The anti-PD-1 immuno-oncology drug Opdivo (nivolumab) has emerged as a new treatment option for the first-line treatment of metastatic urothelial cell carcinoma, where platinum-based chemotherapy was the standard of care.

Ono Pharma Korea and BMS Pharmaceutical Korea said the Ministry of Food and Drug Safety (MFDS) has approved Opdivo plus cisplatin plus gemcitabine for the first-line treatment of unresectable or metastatic urothelial cell carcinoma (UCC).

The approval is based on results from a phase 3 clinical trial CheckMate-901 that evaluated the Opdivo combination compared to cisplatin plus gemcitabine in patients with previously unresectable or metastatic UCC who had not received prior therapy.

Results showed that at a median follow-up of 33.6 months, the primary endpoint, median overall survival (mOS), was significantly longer with the Opdivo combination at 21.7 months (95 percent CI, 18.6-26.4) compared to 18.9 months (95 percent CI, 14.7-22.4) with cisplatin plus gemcitabine, with a 22 percent reduction in the risk of death (HR=0.78; 95 percent confidence interval [CI], 0.63-0.96; P=0.02).

Median progression-free survival (mPFS), another primary endpoint, was 7.9 months and 7.6 months with Opdivo and cisplatin plus gemcitabine, respectively, with Opdivo reducing the risk of disease progression or death by 28 percent (HR=0.72; 95 percent CI, 0.59-0.88; P=0.001).

The 12-month progression-free survival rates were 34.2 percent and 21.8 percent for the Opdivo combination and cisplatin plus gemcitabine. The overall response rate (ORR) was 57.6 percent (21.7 percent complete remission) for the Opdivo combination and 43.1 percent (11.8 percent complete remission) for the cisplatin plus gemcitabine combination. Grade 3 or higher adverse events occurred in 61.8 percent and 51.7 percent of patients.

Opdivo won approval in Korea in August 2017 as a monotherapy for treating patients with locally advanced or metastatic urothelial cell carcinoma whose disease progressed after platinum-based chemotherapy. In February 2022, it also got the nod as postoperative adjuvant therapy for patients with muscle-invasive bladder cancer (MIBC) at high risk of recurrence after radical resection.

In addition, the CheckMate-901 pivotal trial evaluating the combination of Opdivo plus Yervoy (ipilimumab) vs. standard of care in patients with previously unresectable or metastatic urothelial cell carcinoma is ongoing.

While the first-line treatment of metastatic urothelial cell carcinoma has been slow to develop, with platinum-based chemotherapy being the standard of care for the past 30 years, many immuno-oncology agents have recently shown promising clinical results.

Similar to CheckMate 901, the phase 3 KEYNOTE-A39 (EV-302) study, presented at last year's European Society for Medical Oncology Annual Meeting (ESMO 2023), showed that the mOS of the combination of the anti-PD-1 immuno-oncology drug Keytruda (pembrolizumab) and the antibody-drug conjugate (ADC) Padcev (enfortumab vedotin) stood at 31.5 months, reducing the risk of death by 53 percent compared to standard of care (16.1 months), (HR=0.47 [95 percent CI: 0.38-0.58]; P<0.00001).