Adjuvant Nivolumab Improves DFS in High-Risk Muscle-Invasive Urothelial Carcinoma

Adjuvant nivolumab (Opdivo) was found to result in a significant improvement in disease-free survival (DFS) compared with placebo in patients with high-risk muscle-invasive urothelial carcinoma, including those whose tumors expressed PD-L1 of 1% or higher, meeting the primary end points of the phase 3 CheckMate-274 trial (NCT02632409).¹

CheckMate-274 is the first phase 3 trial to demonstrate a reduction in the risk of relapse within the adjuvant setting for this patient population, according to Bristol Myers Squibb. Results also showed no significant differences in the toxicity profile of the agent compared with what has been observed in its use in solid tumors.

“With currently available therapies, more than 50% of patients with bladder cancer will experience recurrence after surgery, and each year, the disease takes the lives of nearly 200,000 patients,” Matthew Galsky, MD, professor of medicine, director of Genitourinary Medical Oncology, director of the Novel Therapeutics Unit, and co-director of the Center of Excellence for Bladder Cancer, at Tisch Cancer Institute and the Icahn School of Medicine at Mount Sinai, stated in a press release.

“Advances like immunotherapy have helped bring hope to patients across a growing number of cancer types, including previously treated advanced urothelial carcinoma,” added Galsky. “The positive results from CheckMate-274 point to the potential for nivolumab to become a new standard of care in the adjuvant setting, extending DFS for post-surgery patients with muscle-invasive bladder cancer without the use of chemotherapy.”

In the randomized, double-blind, multicenter phase 3 trial, investigators set out to examine the safety and effectiveness of nivolumab versus placebo in patients with muscle-invasive urothelial cancer who are at increased risk of recurrence following radical surgery.

To be eligible for participation, patients had to have invasive urothelial cancer at high risk of recurrence that had originated in the bladder, ureter, or renal pelvis.² Patients also needed to have undergone radical surgical resection within the last 120 days before study start. Disease free status had to be determined by imaging within 4 weeks of dosing with nivolumab and tumor tissue had to be made available for biomarker analysis. If they had not received previous neoadjuvant cisplatin chemotherapy, they had to have been ineligible or have refused adjuvant cisplatin-based treatment.

If patients had partial bladder or kidney removal; had received secondary treatment after surgical removal of their disease; had active, known, or suspected autoimmune disease; a previous malignancy that had been active within 3 years before treatment beyond locally curable cancers; or had a condition that required systemic treatment with corticosteroids or other immunosuppressive medications, they were not permitted for inclusion.

A total of 709 participants were randomized in a 1:1 fashion to receive either nivolumab or placebo for the duration of 1 year. The primary end point of the trial was DFS in the intent-to-treat population and in the subgroup of those with tumors that express PD-L1 of 1% or greater. Key secondary end points included overall survival, non-urothelial track recurrence-free survival, and disease-specific survival.

“As we advance the science of immunotherapy, we’re discovering that these treatments may play an important role in earlier stages of cancer, when the immune system is generally more intact and potentially more responsive,” Mark Rutstein, vice president of Opdivo Development at Bristol Myers Squibb, added in the release. “With the positive results from CheckMate-274, [nivolumab] has now demonstrated improved efficacy in the adjuvant treatment of 3 tumor types, including bladder cancer, melanoma, and esophageal/gastroesophageal junction cancer, as part of our broad development program across earlier stages of cancer.”

Bristol Myers Squibb plans to complete a full assessment of the findings from the trial and to work closely with investigators to present the results at an upcoming medical meeting. The company has also expressed plans to submit results from the trial to health authorities. The trial will continue as planned to permit examination of its secondary end points.

References

1. Opdivo (nivolumab) significantly improves disease free-survival vs placebo as adjuvant therapy for patients with high-risk, muscle-invasive urothelial carcinoma in phase 3 CheckMate-274 trial. News release. September 24, 2020. Accessed September 25, 2020. https://bit.ly/3336buX.
2. An investigational immuno-therapy study of nivolumab, compared to placebo, in patients with bladder or upper urinary tract cancer, following surgery to remove the cancer (CheckMate 274). ClinicalTrials.gov. Updated September 10, 2020. Accessed September 25, 2020. https://clinicaltrials.gov/ct2/show/NCT02632409.