Bristol Myers Squibb’s Opdivo has won the FDA’s go-ahead in previously untreated bladder cancer. But the drug’s market potential in this indication may be limited as its PD-1 rival, Merck & Co.’s Keytruda, has impressed in a high-profile treatment combo.
The FDA on Wednesday approved Opdivo, used in combination with the chemotherapies cisplatin and gemcitabine, for the first-line treatment of unresectable or metastatic urothelial carcinoma. The regimen’s composition means that only patients who are eligible for cisplatin can receive it.
The cisplatin requirement effectively reduces the bladder cancer patient population eligible for the new regimen by half. And it puts Opdivo behind Keytruda, which in December secured approval—in its much-acclaimed combination with Astellas and Pfizer’s antibody-drug conjugate (ADC) Padcev—in a broad first-line population regardless of a patient’s eligibility for chemo.
In terms of efficacy, Opdivo-chemo also appeared to place behind Keytruda-Padcev. In fact, during a discussion at the European Society for Medical Oncology meeting in October, when both regimens’ phase 3 data were presented, Andrea Apolo, M.D., a National Cancer Institute expert in bladder cancer research, stated that the Keytruda-Padcev combo “takes first place as the best first-line regimen in urothelial carcinoma.”
In the CheckMate-901 trial, Opdivo and chemo reduced the risk of death by 22% compared with chemo alone. Patients on the BMS regimen lived a median 21.7 months, compared with 18.9 months for those in the chemo arm.
By comparison, in the EV-302 study, Keytruda and Padcev cut the risk of death by a whopping 53% compared with chemo in a group that also included patients who were ineligible for cisplatin. The median overall survival for the novel combo was 31.5 months, versus 16.1 months for chemo.
For the cisplatin-eligible subgroup, the Keytruda-Padcev pairing slashed the risk of death by 47%, with a median overall survival result of 31.5 months, versus 18.4 months for chemo.
Still, during an interview, BMS’ chief medical officer, Samit Hirawat, M.D., argued that the Opdivo-chemo combo has a role to play, just as how chemotherapy in general is still relevant despite the availability of targeted therapies and antibody drugs.
Besides Opdivo and Keytruda, Merck KGaA’s PD-L1 inhibitor Bavencio is allowed as a first-line maintenance therapy in bladder cancer patients who’ve responded to a round of chemo. Wednesday’s approval makes Opdivo part of the first concurrent immunotherapy-chemo combo for this patient population.
Despite the latest regulatory advance for Bristol’s star checkpoint inhibitor, the drug has weathered a prior setback in first-line bladder cancer. Previously, the CheckMate-901 trial produced a negative readout for Opdivo’s combination with BMS’ CLTA-4 inhibitor Yervoy, as the pure-immunotherapy regimen failed to top chemo on overall survival in first-line PD-L1-positive bladder cancer.
The study has one more readout expected this year for Opdivo and Yervoy in a group of cisplatin-ineligible patients.