NEW YORK – Bristol Myers Squibb said on Tuesday that in the Phase III CheckMate-274 trial, adjuvant treatment with nivolumab (Opdivo) nearly doubled disease-free survival in high-risk muscle-invasive urothelial cancer patients compared to placebo, and had an even greater benefit in patients with PD-L1-positive tumors.
The company said it will discuss this data with regulators, indicating it is planning to seek marketing approval for nivolumab as an adjuvant treatment for bladder cancer. Such an approval would allow BMS to market the drug to patients with earlier-stage disease. Currently, the checkpoint inhibitor is approved in the US for locally advanced or metastatic urothelial cancer patients who have progressed on platinum chemotherapy or within a year of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
The CheckMate-274 trial randomized approximately 700 surgically resected, high-risk muscle-invasive urothelial carcinoma patients to receive either nivolumab or placebo in the adjuvant setting; a subset of patients expressed PD-L1 in more than 1 percent of tumor cells. Patients were allowed to receive chemotherapy in the neoadjuvant setting to shrink their tumors before surgical resection.
In the overall study population, including those with and without PD-L1-expressing tumors, median disease-free survival was 21 months in the nivolumab arm, compared to nearly 11 months in the placebo arm, marking a 30 percent reduction in the risk of disease recurrence or death.
In the PD-L1-positive subgroup, the benefits of adjuvant nivolumab treatment were more pronounced, resulting in a 47 percent reduction in the risk of disease recurrence or death. The median disease-free survival among patients taking nivolumab was not reached, but was 10.8 months for those on placebo.
In the trial, nivolumab also improved non-urothelial tract recurrence-free survival (NUTRFS), defined as the time that patients lived without disease recurrence outside of the bladder, ureters, or renal pelvis. Median NUTRFS was 24.6 months in all patients treated with nivolumab, compared to around 14 months in the placebo arm. In PD-L1-positive patients, median NUTRFS was not reached for those on nivolumab compared to around 11 months in the placebo arm.
"By moving immunotherapy into earlier stages of cancer, we may have the chance to disrupt the course of the disease, reducing recurrence and leading to better outcomes for patients," Dana Walker, development program lead for genitourinary cancers at BMS, said in a statement. "Opdivo-based therapy has now shown benefit not only as an adjuvant treatment in urothelial cancer, but also in earlier-stage melanoma, esophageal, and lung cancer. We look forward to working with regulatory authorities globally with the goal of bringing this treatment option to those who may benefit."
BMS will present detailed data from the trial at the American Society of Clinical Oncology Genitourinary Cancers Symposium on Feb. 12.