Nivolumab/Chemo Approval Adds Options for Urothelial Carcinoma, Expert Says

Scott T. Tagawa, MD, MS, FACP, FASCO, spoke with CancerNetwork^® about the FDA approval of nivolumab (Opdivo) plus cisplatin and gemcitabine as first-line treatment for unresectable or metastatic urothelial carcinoma.¹ This approval was based on results from the phase 3 CheckMate-901 trial (NCT03036098).²

The trial, which combined nivolumab with platinum-based chemotherapy, showed promise in treating advanced urothelial carcinoma.Prior to this, pembrolizumab (Keytruda) appeared to be the standard first-line therapy for patients who are ineligible for cisplatin. Tagawa, a professor of Medicine and Urology at Weill Cornell Medicine and an attending physician at NewYork-Presbyterian – Weill Cornell Medical Center, highlighted that the CheckMate-901 trial was the first to show positive results for an immune checkpoint inhibitor used in combination with cisplatin-based chemotherapy as first-line therapy for urothelial carcinoma.

Tagawa also discussed enfortumab vedotin-ejfv (EV; Padcev) plus pembrolizumab (Keytruda) as another treatment option for urothelial carcinoma, but noted that some patients may not be candidates to receive EV.

Transcript:

If we think about PD-1 and PD-L1 in advanced urothelial carcinoma, we’re looking for ways to make it work. Platinum-refractory [disease] was the first entry, and it worked. Multiple agents worked, with pembrolizumab having an [increased] survival benefit and becoming the most standard agent. We did a number of trials in the first-line setting [using] a bunch of combinations that were negative overall. But maintenance immunotherapy like avelumab [Bavencio] worked, so extending first-line therapy [worked] as long as they’d have progression. There’s preclinical and clinical data that cisplatin might be more immunogenic than carboplatin. For the first time in the frontline setting, adding an immune checkpoint inhibitor, in this case, the PD-1 inhibitor nivolumab, worked in combination with platinum-based chemotherapy when the platinum [agent] was specifically cisplatin. That’s nice to have. It’s always nice to have additional agents out there.

[The approval] came after the presentation of the phase 3 EV-302 trial [NCT04223856].³ [It assessed the] combination of the antibody drug conjugate enfortumab vedotin, or EV, with pembrolizumab. It was a similar situation that used frontline therapy, although gemcitabine/cisplatin and nivolumab vs EV plus pembrolizumab were not compared. The difference in the control was so much bigger with the EV/pembrolizumab [study]. It’s great to have [multiple options] out there. Some patients might be a candidate for cisplatin but not for EV. It’s a small number, but they might be out there. They also may be candidates for immune checkpoint inhibitors. That could be the indication for gemcitabine/cisplatin plus [nivolumab].

That being said, I think that EV/pembrolizumab is the standard to be beaten or improved upon in the frontline, advanced urothelial carcinoma population. But the more approvals we have, the better it is for our patients.

References

1. FDA approves nivolumab in combination with cisplatin and gemcitabine for unresectable or metastatic urothelial carcinoma. News release. FDA. March 6, 2024. Accessed March 7, 2024. https://shorturl.at/jtwL9
2. van der Heijden MS, Sonpavde G, Powles T, et al. Nivolumab plus gemcitabine-cisplatin versus gemcitabine-cisplatin alone for previously untreated unresectable or metastatic urothelial carcinoma: Results from the phase III CheckMate 901 trial. Presented at: ESMO Congress 2023; October 20-24, 2023; Madrid, Spain. Abstract LBA7.
3. Powles T, Valderrama BP, Gupta S, et al. Enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer. N Engl J Med. 2024;390(10):875-888. doi:10.1056/NEJMoa2312117.