Dr Sonpavde on the Efficacy of Frontline Nivolumab Plus Chemotherapy in Metastatic Urothelial Carcinoma

Guru P. Sonpavde, MD, medical director, Genitourinary (GU) Oncology, assistant director, the Clinical Research Unit, the Christopher K. Glanz Chair, Bladder Cancer Research, AdventHealth Cancer Institute, discusses the significance of data from the phase 3 CheckMate 901 trial (NCT03036098) of concurrent frontline nivolumab plus chemotherapy in metastatic or unresectable urothelial carcinoma.

The primary objective of this randomized, open-label trial was to assess overall survival (OS) and progression-free survival (PFS) with the study combination compared with chemotherapy alone. A total of 608 cisplatin-eligible patients with previously untreated, metastatic or unresectable urothelial carcinoma were included on the study, Sonpavde details. Patients were randomized 1:1 to nivolumab to standard-of-care gemcitabine/cisplatin followed by nivolumab maintenance therapy, or gemcitabine/cisplatin, he adds.

Findings presented at the 2023 ESMO Congress showed that patients who received nivolumab alongside chemotherapy demonstrated a statistically significant improvement in both OS and PFS, Sonpavde reports. The median OS increased from 18.9 months (95% CI, 14.7-22.4) with chemotherapy alone to 21.7 months (95% CI, 18.6-26.4) with the combination. This translates to a 22% reduction in the risk of death (HR, 0.78; 95% CI, 0.63-0.96; P = .0171). Notably, OS benefit with the nivolumab regimen was observed across all subgroups.

The median PFS with the nivolumab combination was 7.9 months (95% CI, 7.6-9.5) compared with 7.6 months (95% CI, 6.1-7.8) with chemotherapy alone; this reduced the risk for progression by 28% (HR, 0.72; 95% CI, 0.59-0.88; P = .0012). Despite the numerically similar median PFS in both trial arms, separation of the survival curve at 6 months indicated the combination regimen's superiority. Moreover,12- and 24- months PFS rates were 34.2% and 23.5% with the combination regimen, respectively. Corresponding PFS rates in the chemotherapy arm were 21.8% and 9.6%.

Additionally, overall response rates were higher in the nivolumab arm vs chemotherapy arm, at 57.6% (95% CI, 51.8%-63.2%) and 43.15 (95% CI, 37.5%-48.9%). The complete response (CR) rate was nearly doubled (21.7% vs 11.8%) and the duration of CR was almost 3 times longer in the nivolumab arm (37.1 months) vs the chemotherapy arm (13.2 months), Sonpavde states. Critically, prolonged CRs were seen with the nivolumab regimen despite its shorter treatment duration of no more than 2 years, he notes. In the nivolumab regimen, chemotherapy is administered for up to 6 cycles, after which treatment with nivolumab continues until disease progression or unacceptable toxicity, Sonpavde says. This finite duration of chemotherapy could improve quality of life for these patients, and may be considered for patients with lymph node–only disease, Sonpavde explains.

Overall, these data indicate that the addition of checkpoint inhibition to standard chemotherapy regimens can improve survival outcomes in this population, he concludes.