Nivolumab/Chemo Extends Survival In Urothelial Carcinoma Sub-Study

Frontline nivolumab (Opdivo) plus cisplatin-based chemotherapy improved survival among patients with unresectable or metastatic urothelial carcinoma in a sub-study of the phase 3 CheckMate -901 trial (NCT03036098), thereby meeting the study’s primary survival end points, according to a press release from Bristol Myers Squibb.¹

Patients who received nivolumab and cisplatin-based chemotherapy followed by nivolumab monotherapy experienced statistically significant benefits in overall survival (OS) and progression-free survival (PFS) compared with those who received standard-of-care cisplatin-based chemotherapy alone. Investigators identified no new safety signals, and the safety profile of the experimental regimen matched the known profiles of the component agents.

Nivolumab has shown clinical benefit in second-line metastatic urothelial carcinoma and in the adjuvant treatment of muscle-invasive urothelial carcinoma among patients at a high risk for recurrence following radical surgery.

Detailed findings are expected at a future medical conference.

“Nivolumab with cisplatin-based chemotherapy is the first immunotherapy-based combination to improve both [OS] and [PFS] in patients with previously untreated unresectable or metastatic urothelial carcinoma who are eligible for cisplatin-based chemotherapy, reinforcing the benefits of [nivolumab]-based treatments seen across a variety of genitourinary cancers, including durable survival in advanced renal cell carcinoma and a reduced risk of recurrence in resectable muscle-invasive urothelial carcinoma,” Dana Walker, MD, MSCE, vice president and global program lead of genitourinary cancers at Bristol Myers Squibb, said in the press release.

“We are encouraged by these positive results and remain steadfast in our commitment to bringing new solutions to patients with high unmet needs.”

According to the press release, nivolumab is a PD-1–targeting immune checkpoint inhibitor and was a first agent of its kind to receive any regulatory approval worldwide. It has shown clinical benefit in second-line metastatic urothelial carcinoma and in the adjuvant treatment of muscle-invasive urothelial carcinoma among patients at a high risk for recurrence following radical surgery.

Nivolumab had previously missed the end point of OS in CheckMate-901. When combined with ipilimumab (Yervoy), the nivolumab failed to prolong OS vs standard-of-care chemotherapy in patients with a PD-L1 expression of 1% or more.²

Investigators assessed outcomes in 608 patients for the sub-study. Patients were randomly assigned to receive either nivolumab at a dose of 360 mg plus gemcitabine/cisplatin every 3 weeks or chemotherapy alone. OS and PFS are the primary end points. EORTC QLQ-C30 Global Health Status scores are among the trial’s secondary end points.

The trial included patients 18 years and older with histological or cytological evidence of metastatic or surgically inoperable transitional cell cancer of the urothelium involving the renal pelvis, ureter, bladder or urethra. To be eligible for enrollment, patients also could not have undergone prior systemic chemotherapy for metastatic or surgically inoperable urothelial cancer, and they must have had an ECOG performance status of 0 or 1.

Patients with disease suitable for local therapy with curative intent were excluded from eligibility. Other exclusion criteria included any serious or uncontrolled medical disorder deemed to possibly increase risk or interfere with the study, and any prior treatment with an anti–PD-1, anti–PD-L1, anti–PD-L2, anti-CD137, or anti–CTLA-4 antibody.

Reference

1. Opdivo (nivolumab) in combination with cisplatin-based chemotherapy shows overall survival and progression-free survival benefit for cisplatin-eligible patients with unresectable or metastatic urothelial carcinoma in the phase 3 CheckMate -901 trial. News Release. Bristol Myers Squibb. July 11, 2023. Accessed July 13, 2023. https://bit.ly/3rjPr10
2. Bristol Myers Squibb provides update on CheckMate -901 trial evaluating opdivo (nivolumab) plus yervoy (ipilimumab) as first-line treatment for patients with unresectable or metastatic urothelial carcinoma. News release. Bristol Myers Squibb. May 16, 2022. Accessed July 13, 2023. https://bit.ly/3LnPCg1