Treatment with the immunotherapy nivolumab with or without cisplatin-based chemotherapy following radical surgery significantly improved disease-free survival in patients with muscle-invasive urothelial carcinoma, irrespective of their PD-L1 status, according to a study that will be presented by Dean F. Bajorin, MD, and colleagues at the 2021 Genitourinary Cancers Symposium, taking place virtually February 11 to 13 (Abstract 391).
The results come from the phase III CheckMate 274 trial of adjuvant nivolumab in patients who underwent radical surgery for high-risk muscle-invasive urothelial carcinoma of the bladder, ureter, or renal pelvis.
Dean F. Bajorin, MD
The standard-of-care treatment for muscle-invasive urothelial carcinoma is cisplatin-based neoadjuvant therapy followed by radical surgery—removal of the bladder. However, some patients may be ineligible to receive cisplatin due to factors like inadequate kidney function. Adjuvant nivolumab could provide a treatment option for these patients to reduce the risk of recurrent cancers and death.
CheckMate 274 Details
The study involved 709 patients with muscle-invasive urothelial carcinoma who underwent radical surgery with or without neoadjuvant cisplatin-based chemotherapy. There was a high risk for recurrence based on the tumor stage at surgery. Patients were randomly assigned to receive nivolumab or placebo every other week for 1 year.
Key Findings
Median disease-free survival was significantly longer for patients who received postsurgery treatment with nivolumab (median = 21 months) compared with those who received placebo (median = 10.9 months). Disease-free survival for a subset of patients with PD-L1–positive tumors was also improved with nivolumab (median = not reached by the time of analysis).
“Nivolumab is the first immune therapy to be used in the adjuvant setting that provides a statistically significant and clinically meaningful improvement in disease-free survival for patients with high-risk muscle-invasive urothelial carcinoma after radical surgery with curative intent, irrespective of PD-L1 status,” said lead author Dr. Bajorin, a medical oncologist at Memorial Sloan Kettering Cancer Center.
KEY POINTS
- Median disease-free survival was significantly longer for patients who received postsurgery treatment with nivolumab (median = 21 months) compared with those who received placebo (median = 10.9 months).
- Disease-free survival for a subset of patients with PD-L1–positive tumors was also improved with nivolumab (median = not reached by the time of analysis).
More serious treatment-related side effects (grade 3–4) were seen among patients who received nivolumab (17.9%) than those who received placebo (7.2%). The most common grade 3 or higher treatment-related side effects were diarrhea, colitis, and pneumonitis in patients in the nivolumab arm, and colitis, diarrhea, gamma-glutamyl transferase increase, and hepatitis in patients in the placebo arm.
“Even with the current standard of care—surgery with or without presurgery chemotherapy—muscle-invasive urothelial carcinoma has a high risk of recurring. These new findings show that treating patients at highest risk of recurrence with an immunotherapy after surgery can help extend the time until the disease returns,” said Robert Dreicer, MD, MS, MACP, FASCO, ASCO expert in genitourinary cancers.
Next Steps
In order to examine the impact of nivolumab on overall survival and cancer-specific survival, longer follow-up is needed.
Disclosure: The study received funding from Bristol Myers Squibb in collaboration with ONO Pharmaceutical Company Ltd. For full disclosures of the study authors, visit coi.asco.org.
