Dr Sharma on the CheckMate 901 Study in Advanced Urothelial Cancer

“Although you can’t compare between trials…we have seen a larger percentage of patients have a response to the enfortumab vedotin and pembrolizumab combination, which is why I think it is in the forefront of most providers’ treatment armamentariums.”

Janaki Neela Sharma, MD, assistant professor, clinical medicine, Genitourinary Medical Oncology, University of Miami Health Systems, discusses key data from the phase 3 CheckMate 901 study (NCT03036098) and where nivolumab (Opdivo) plus chemotherapy fits into the frontline treatment setting for advanced urothelial cancer.

Notably, data from this clinical trial supported the March 2024 FDA approval of frontline nivolumab plus cisplatin and gemcitabine for the frontline treatment of adult patients with unresectable or metastatic urothelial carcinoma. This trial showed that the combination significantly improved overall survival (OS) and progression-free survival vs cisplatin/gemcitabine alone. CheckMate 901 included randomization to receive either nivolumab or placebo alongside chemotherapy, followed by maintenance with nivolumab or placebo, Sharma begins. The trial evaluated whether adding nivolumab could enhance outcomes compared with standard chemotherapy.

The trial demonstrated a median OS of 21.7 months (95% CI, 18.6-26.4) with nivolumab plus chemotherapy, an improvement over the control arm’s median OS of 18.9 months (95% CI, 14.7-22.4); these findings align with historical data showing median OS lengths of approximately 18 to 20 months with traditional chemotherapy in this setting, she reports. This survival benefit of nivolumab highlights the potential of using nivolumab combined with chemotherapy as a viable frontline treatment option, Sharma says.

In terms of response rates, nivolumab plus chemotherapy achieved an overall response rate (ORR) of 57.6% (95% CI, 51.8%-63.2%), reflecting solid efficacy, she continues. However, when compared indirectly with the enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) combination studied in the phase 3 EV-302/KEYNOTE-A39 trial (NCT04223856), which generated an ORR of 67.7% (95% CI, 63.1%-72.1%) in patients with untreated locally advanced or metastatic urothelial cancer, nivolumab plus chemotherapy appeared to elicit less robust responses, Sharma emphasizes. Although cross-trial comparisons should be interpreted cautiously, these data indicatethat enfortumab vedotin plus pembrolizumab may offer superior response rates vs nivolumab plus chemotherapy, positioning the former as a preferred frontline treatment in many cases, she concludes.