ESMO: Bristol Myers' Opdivo chalks up bladder cancer win. But a rival combo casts long shadow

Bladder cancer hasn’t been the easiest tumor type to tackle for immunotherapies. Bristol Myers Squibb has found success here with its Opdivo, but the win was overshadowed by competitor data.

Adding Opdivo to cisplatin-based chemotherapy lowered the risk of death from previously untreated bladder cancer by 22%, according to data presented at the European Society for Medical Oncology annual meeting. Compared with chemotherapy alone, Opdivo and chemo extended the median time patients lived by 2.8 months to 21.7 months.

The data came from an analysis of cisplatin-eligible patients enrolled in the phase 3 CheckMate-901 trial, which also includes patients who can’t take cisplatin. The cisplatin-ineligible part of the study hasn’t read out yet.

If approved, Opdivo would compete with Merck KGaA’s Bavencio, which is approved as a first-line maintenance therapy in patients who have not had disease progression following initial platinum-containing chemotherapy. But Astellas, Seagen and Merck & Co.’s combination of the PD-1 inhibitor Keytruda and the antibody-drug conjugate Padcev may be a more formidable competitor.

Bavencio got its first-line maintenance nod in mid-2020 based on data from the phase 3 Javelin Bladder 100 study showing it reduced the risk of death by 31% compared with best supportive care.

The data from the Javelin trial and Opdivo’s current CheckMate-901 can’t be compared side by side. In the Bavencio trial, investigators only studied the medicine in patients who had responded to an initial round of cisplatin or carboplatin treatment. In the BMS study, Opdivo was combined with cisplatin from the beginning.

“When you have a transformational therapy that has shown an overall survival benefit when given upfront as a first-line treatment, there is no reason to hold it just because there may be a possibility of using it later on,” Bristol Myers’ chief medical officer, Samit Hirawat, M.D., said of the two regimens in an interview.

The U.S.-based Merck & Co. had previously tested adding Keytruda to chemo upfront in first-line bladder cancer. But the Keynote-361 trial failed to show a statistically significant benefit for the Keytruda-chemo pairing, which only reduced the risk of death by 14% over chemo alone. The FDA later limited Keytruda’s first-line bladder cancer indication, allowing it as a single agent only for patients who aren’t eligible for any platinum-containing chemotherapy.

But at ESMO 2023, Merck and its partners have come back with positive data for Keytruda’s combination with Padcev.

The Padcev-Keytruda combo significantly prolonged overall survival, reducing the risk of death by 53% compared with platinum-based chemo, according to data from the closely watched EV-302 trial.

The EV-302 trial included both cisplatin-eligible patients and those who’re not eligible for cisplatin but can take carboplatin. Opdivo’s current data are only from cisplatin-eligible population. In a subgroup analysis of the cisplatin-eligible patients in EV-302, the Padcev-Keytruda combo cut the risk of death by 47% versus chemo. The magnitude of improvement was more than double that of the Opdivo-chemo regimen.

As an antibody-drug conjugate, Padcev is essentially a guided cytotoxic agent that can go after tumors in a more targeted way compared with traditional chemotherapy.

Hirawat suggested that BMS’ Opdivo-chemo combo will still have a role to play. He pointed to how chemotherapy in general has been around for decades and are still relevant despite the availability of targeted therapies and monoclonal antibodies.

“In the future, if you’re able to find chemo-sparing regimens that are safe and efficacious and transformational, we certainly should move away,” Hirawat said. “But I don’t think this is the time.”

But to Andrea Apolo, M.D., from the National Cancer Institute, an expert invited by ESMO to discuss the two studies, there’s a clear winner between the two regimens.

Padcev and Keytruda “takes first place as the best first-line regimen in urothelial carcinoma,” Apolo said during an ESMO presentation. And by the loud and long applaud following that comment, the audience agreed.