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ASCO GU: Bristol Myers touts first-in-class Opdivo win in muscle-invasive bladder cancer

In the PD-1/L1 field, Merck & Co.’s Keytruda, Roche’s Tecentriq, and Pfizer and Merck KGaA’s Bavencio all have their clinical wins in different bladder cancer populations. Now, Bristol Myers Squibb’s Opdivo has one of its own.

In high-risk muscle-invasive urothelial carcinoma, the use of Opdivo after surgery cut patients’ risk of disease returning or death by 30% over placebo. The data was released for presentation at the American Society of Clinical Oncology Genitourinary Cancers Symposium.

Bristol Myers was quick to point out that the CheckMate-274 win marks the first positive phase 3 readout for a checkpoint inhibitor in this particular bladder cancer setting.

It’s estimated that about 50% of patients diagnosed with muscle-invasive bladder cancer will see their cancer return after surgery. In CheckMate-274, though, Opdivo almost doubled the time patients lived without recurrence; the BMS drug helped patients stay disease-free for a median of 21.0 months, versus 10.9 months for placebo.

The benefit was even more pronounced in patients whose tumors expressed biomarker PD-L1, with the risk reduction expanding to 47%. In that subpopulation, the median time before the disease returned hadn’t been reached for Opdivo, compared with 10.8 months for placebo.

Opdivo cut the risk of disease recurrence outside the bladder, ureters or renal pelvis by 28% in the wider patient group and by 46% among PD-L1-positive patients. That secondary endpoint is important because oncologists want to know if the recurrence is more distant, making it more challenging to keep patients alive, Jonathan Cheng, M.D., BMS’ head of oncology development, explained in an interview.

The company is talking to the FDA about the data. Disease-free survival data in bladder cancer has been a clinically relevant endpoint used to support FDA filings in the past, Cheng said, and meanwhile, investigators are still following the patients to see if Opdivo can prolong lives. 

The bladder cancer arena is full of PD-1/L1 competition. So far, the drugs have mostly managed to find their niche markets, but it may not be long until they have challengers to face.

Opdivo, for its part, has been approved in previously treated locally advanced or metastatic bladder cancer since 2017. Keytruda quickly followed into the second-line setting and simultaneously added a front-line use in cisplatin-ineligible patients. But the FDA soon limited that first-line use to PD-L1-positive patients after noting Keytruda might perform worse than chemotherapy in other cases.

An update last year showed neither solo Keytruda nor a Keytruda-chemo combo was able to stall the progression of tumors or prolong patients’ lives compared with chemo. That flop made Roche’s Tecentriq the only PD-1/L1 to stall disease progression in first-line metastatic bladder cancer. But BMS is pitting its dual immuno-oncology regimen Opdivo and Yervoy against chemo in previously untreated patients in the CheckMate-901 phase 3 trial.

Bavencio, meanwhile, has a unique FDA go-ahead in the so-called first-line maintenance setting, for patients who have completed an initial round of chemo and haven’t seen their disease progress.

Roche previously aimed Tecentriq at muscle-invasive disease, too. But the drug failed to move the needle when it came to fending off cancer recurrence or death, with a risk reduction of merely 11% against simple observation in the phase 3 IMvigor010 trial.

Besides BMS, AstraZeneca is also testing the use of Imfinzi and chemo pre-surgery followed by Imfinzi monotherapy postsurgery in muscle-invasive bladder cancer in the phase 3 Niagara study.

Merck’s pursuing a different approach with the phase 3 Keynote-992 trial, trying to see if adding Keytruda to chemoradiotherapy can stall the time to disease progression in patients with muscle-invasive disease.

Beyond the muscle-invasive type, BMS also wants to see if Opdivo has a place in early-phase non-muscle-invasive bladder cancer (NMIBC). It’s adding the PD-1 drug to standard bacterial treatment BCG to see if the pairing can help high-risk patients with persistent or recurrent disease after BCG. In NMIBC, Keytruda already boasts a first-in-class approval for patients unresponsive to BCG.

“We do want to encompass the gamut of understanding as to how checkpoint inhibitors, specifically [Opdivo], can have an impact in bladder cancer,” Cheng said.