Bristol Myers Squibb Reports Breakthrough with Immunotherapy Opdivo

Bristol Myers Squibb recently announced that its immunotherapy, Opdivo (nivolumab), improved disease-free survival versus a placebo for patients with high-risk, muscle-invasive bladder cancer in a Phase 3 clinical trial.

The CheckMate-274 trial is the first and only Phase 3 trial in which immunotherapy reduced the risk of relapse in the adjuvant setting for these patients, researchers said. 

The trial enrolled 709 patients who were randomized one to one to receive Opdivo or a placebo for up to one year. 

Opdivo met its primary endpoints of improving disease-free survival versus placebo in both all randomized patients and patients whose tumor cells expressed PD-L1 greater than one percent.

The safety profile of the drug was also consistent with previous studies. 

“Advances like immunotherapy have helped bring hope to patients across a growing number of cancer types, including previously treated advanced urothelial carcinoma,” said Matthew Galsky, MD, professor of medicine and director of genitourinary medical oncology, director of the novel therapeutics unit, and co-director of the Center of Excellence for Bladder Cancer at The Tisch Cancer Institute and the Icahn School of Medicine at Mount Sinai.

“The positive results from CheckMate -274 point to the potential for nivolumab to become a new standard of care in the adjuvant setting, extending disease-free survival for post-surgery patients with muscle-invasive urothelial cancer without the use of chemotherapy,” Galsky added in the announcement. 

Bristol Myers stated that it will complete a full evaluation of the CheckMate-274 data, work with investigators to present the results, and submit the data to health authorities. 

Even with the available therapies, over 50 percent of patients with bladder cancer will experience recurrence after surgery, Galsky noted. And nearly 200,000 patients die from the disease each year. 

“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,” said Mark Rutstein, vice president, Opdivo development, Bristol Myers Squibb.  

“Opdivo has now demonstrated improved efficacy in the adjuvant treatment of three 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 highlighted that the company mainly focuses on immune cell therapy, including CAR T cell agents, and gene therapies that target specific pathways. 

Last week, Bristol Myers Squibb announced that over half (53.4 percent) of advanced renal cell carcinoma patients treated with Opdivo and Yervoy in a Phase 3 clinical trial were alive after four years. 

The CheckMate-214 trial also found that, in contrast, the overall survival rate for standard care, sunitinib, was 43.4 percent.

The combination of the immunotherapies also showed a four-year overall survival rate of 50 percent, compared to 35.8 percent with sunitinib. And Opdivo showed a 65 percent overall response rate, while sunitinib showed a 50 percent overall response rate.

Although pharmaceutical companies are continuing to invest in immunotherapy programs, not all patients are responding to the innovative treatment, according to a March JAMA Network Open study.

In 2018, the FDA limited the use of pembrolizumab and atezolizumab to patients with bladder cancer who were not eligible for cisplatin-containing therapy.

In the first study scenario researchers used was 2019 estimations assuming that FDA limits were specific to pembrolizumab and atezolizumab. The second scenario was 2019 estimations assuming that all immunotherapies approved for bladder cancers are limited to patients with programmed death-ligand 1 expression who are cisplatin ineligible. 

Researchers found that cancer patients eligible for immune checkpoint inhibitor therapy was 38.5 percent and 36.1 percent, respectively. And the estimated total response to these drug scenarios was 11.4 percent and 10.9 percent, respectively.  

So, while immunotherapy has the potential to reshape cancer worldwide, strong partnerships are vital for extensive clinical research and product development.