Upfront Nivolumab/Chemotherapy Prolongs Survival in Unresectable/Metastatic Urothelial Carcinoma


A further look at nivolumab combined with cisplatin-based chemotherapy outside of the primary CheckMate-901 study shows survival benefit for the study combination.


Matthew D. Galsky, MD

Statistically significant and clinically meaningful enhancements in progression-free survival (PFS) and overall survival (OS) have been exhibited in a sub study of the phase 3 CheckMate-901 clinical trial (NCT03036098), according to final analysis results.1

The sub study is investigating nivolumab (Opdivo) in combination with cisplatin-based chemotherapy compared with standard-of-care cisplatin-based regimens in first-line patients with unresectable or metastatic urothelial carcinoma.

The results also showed that treatment was tolerable, and the safety profiles of each agent were consistent with prior knowledge. Further assessment of the data will ensue, and full results will be shared with regulatory authorities and presented at an upcoming medical conference.

“Chemotherapy and immune checkpoint blockade represent 2 critical backbones of treatment for metastatic urothelial cancer. Based on the immunomodulatory effects of chemotherapy, as well as several studies in other solid tumors demonstrating improved outcomes combining chemotherapy and immune checkpoint blockade in other solid tumors, a series of similar trials were launched in metastatic urothelial cancer. Unfortunately, these studies did not show improved outcomes in patients with metastatic urothelial cancer. A nuance to these prior studies was that they pooled cisplatin-eligible and cisplatin-ineligible patients in the same trials. Those trials demonstrated a signal that immune checkpoint blockade may pair better with gemcitabine plus cisplatin vs gemcitabine plus carboplatin and a series of translational analyses further supported that concept,” Matthew Galsky, MD, professor of medicine (hematology and medical oncology), director of genitourinary oncology, co-director of the Center for Excellence for Bladder Cancer, and associate director of translational research at Tisch Cancer Institute, told Targeted Oncology™.

Bladder Cancer: High grade transitional cell carcinoma (TCC), Urothelial carcinoma | Image Credit: © Saiful52 -www.stock.adobe.com

Image Credit: © Saiful52 -www.stock.adobe.com

The sub study included 608 patients eligible for cisplatin-based chemotherapy. Patients were randomized to either nivolumab 360 mg with chemotherapy or chemotherapy alone. It follows patients with previously untreated, unresectable, or metastatic urothelial carcinoma.1 The primary study investigated OS and PFS in the all-randomized population, as well the PD-L1-positive population as both primary and secondary end points. Secondary end points of the study also included health-related quality of life according to the European Organisation for Research and Treatment of Care QLQ-C30 Global Health Status score in all randomized patients and the cisplatin-eligible population.2

“Today’s news is yet another example of the power of immunotherapy combinations to transform outcomes for patients with cancer. [Nivolumab] with cisplatin-based chemotherapy is the first immunotherapy-based combination to improve both overall survival and progression-free survival in patients with previously untreated unresectable or metastatic urothelial carcinoma who are eligible for cisplatin-based chemotherapy, reinforcing the benefits of Opdivo-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,” said Dana Walker, MD, MSCE, vice president, global program lead, genitourinary cancers, Bristol Myers Squibb, in a 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...”

A previous announcement about CheckMate-901 showed that the primary end point of OS in PD-L1-positive patients with first-line, unresectable or metastatic disease was not met. However, both studies continue to evaluate patients.3

“CheckMate 901 is the first study of chemotherapy with or without PD-1 blockade in metastatic urothelial cancer that was limited to patients receiving gemcitabine plus cisplatin. This study demonstrating an improvement in PFS and OS represents a key advance, but also provides validation for prior hypotheses regarding the impact of cisplatin- vs carboplatin-containing regimens when combined with immune checkpoint blockade in urothelial cancer,” said Galsky.


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 11, 2023. https://tinyurl.com/4769j68y

2. Study of nivolumab in combination with ipilimumab or standard of care chemotherapy compared to the standard of care chemotherapy alone in treatment of participants with untreated inoperable or metastatic urothelial cancer (CheckMate901). ClincalTrials.gov. Updated July 7, 2023. Accessed July 11, 2023. https://tinyurl.com/3scmcmac

3. 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 11, 2023. https://tinyurl.com/44h87n6f

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