Opdivo Plus Chemotherapy Approved for First-Line Tx of Urothelial Carcinoma

The Food and Drug Administration (FDA) has approved Opdivo (nivolumab) in combination with cisplatin and gemcitabine for the first-line treatment of adults with unresectable or metastatic urothelial carcinoma (UC).

The approval was based on data from the open-label, randomized, phase 3 CheckMate-901 study (ClinicalTrials.gov Identifier: NCT03036098), which evaluated the efficacy and safety of nivolumab, a programmed death receptor-1 blocking antibody, plus cisplatin and gemcitabine in 608 patients with previously untreated unresectable or metastatic UC. 

Study participants were randomly assigned 1:1 to receive either nivolumab plus cisplatin and gemcitabine (up to 6 cycles) followed by nivolumab alone for up to 2 years (n=304) or standard of care chemotherapy alone (cisplatin plus gemcitabine; up to 6 cycles) (n=304). The coprimary endpoints were overall survival (OS) and progression free survival (PFS).

At a median follow-up of 33.6 months, nivolumab plus cisplatin and gemcitabine reduced the risk of death by 22% compared with chemotherapy alone (hazard ratio [HR], 0.78; 95% CI, 0.63-0.96; P =.02); median OS was 21.7 months and 18.9 months, respectively.

The nivolumab combo also reduced the risk for disease progression or death by 28% vs chemotherapy alone (HR, 0.72; 95% CI, 0.59-0.88; P =.001); median PFS was 7.9 months and 7.6 months, respectively.

The objective response rate was 57.6% (22% complete response; 36% partial response) and 43.1% (12% complete response; 31% partial response) in the nivolumab plus cisplatin and gemcitabine and chemotherapy alone groups, respectively. Median duration of response was 9.5 months and 7.3 months in the respective arms. 

The most common adverse reactions reported with nivolumab plus cisplatin and gemcitabine were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, peripheral neuropathy, urinary tract infection, diarrhea, edema, hypothyroidism, and pruritus.

“Bringing Opdivo to the first-line setting in UC with chemotherapy is the latest realization of our history of research and progress in immunotherapy, which has helped transform the treatment landscape for many cancers, including bladder cancer,” said Wendy Short Bartie, senior vice president and general manager, US Hematology and Oncology at Bristol Myers Squibb. “This milestone adds a meaningful expansion to our portfolio of Opdivo-based treatments in genitourinary cancers, where we now have offerings in UC spanning three indications across stages of disease and treatment needs.”