Merck, BMS Score Separate Late-Stage Victories in Bladder Cancer at ESMO

Abdominal Ultrasound_iStock, Victoria Kotlyarchuk

Pictured: Doctor looking at abdominal ultrasound images/iStock, Victoria Kotlyarchuk

Merck and Bristol Myers Squibb presented Phase III readouts for bladder cancer at the European Society for Medical Oncology Congress 2023, both touting strong survival benefits for their respective PD-1 blockers.

In the Phase III KEYNOTE-A39 study, Merck’s blockbuster Keytruda reduced the risk of death by 53% versus chemotherapy when given as a combination regimen with Seagen and Astellas’ Padcev (enfortumab vedotin-ejfv). The study enrolled 886 patients with previously untreated locally advanced or metastatic urothelial carcinoma, regardless of their PD-L1 status.

At the time of the pre-specified analysis, median overall survival (OS) in the Keytruda arm was 31.5 months, compared to 16.1 months in those receiving chemotherapy, representing a more-than 15-month improvement.

Keytruda plus Padcev also led to significantly better progression-free survival (PFS), cutting the risk of death or progression by 55% compared with chemotherapy. Median PFS was 12.5 months in the combo regimen arm, nearly double the 6.3-month PFS in chemotherapy counterparts.

Both survival benefits were highly statistically significant, with p-values less than 0.00001, according to Merck’s announcement.

Merck CMO Eliav Barr called KEYNOTE-A39’s survival data “unambiguous” in a statement, pointing out that the Keytruda-Padcev combo “reduced the risk of death by half when compared to chemotherapy.”

“These results—the first positive Phase III results combining a PD-1 inhibitor and an antibody-drug conjugate in this patient population—have the potential to change the treatment paradigm for previously untreated patients with advanced urothelial cancer,” Barr said.

KEYNOTE-A39 will serve as the confirmatory trial for the Keytruda plus Padcev combo regimen, which is currently under accelerated approval for the first-line treatment of locally advanced or metastatic urothelial carcinoma.

Also at ESMO 2023, BMS unveiled data from the Phase III CheckMate-901 study, showing that its PD-1 inhibitor Opdivo (nivolumab) plus cisplatin-based chemotherapy, followed by Opdivo monotherapy, likewise led to better survival outcomes in patients with unresectable or metastatic urothelial carcinoma.

Compared with standard-of-care cisplatin chemotherapy alone, and after a median follow-up of approximately 33 months, the Opdivo-based regimen cut the risk of death by 22%. Landmark analyses at 12 and 24 months also showed OS rates of 70.2% and 46.9%, respectively, for the Opdivo arm, compared to only 62.7% and 40.7%, respectively, in the chemotherapy control group.

PFS was also better in patients treated with the Opdivo regimen, which reduced the risk of disease progression or death by 28%. Both PFS and OS outcomes were statistically significant, according to the BMS announcement.

BMS also posted exploratory data from CheckMate-901, indicating that nearly twice as many patients reached complete response in the Opdivo group than in the chemotherapy alone arm. Objective response rate and duration of treatment response were likewise better in the Opdivo group.

Results from CheckMate-901 underscore the potential of Opdivo plus cisplatin chemotherapy for the first-line treatment of patients with unresectable or metastatic urothelial carcinoma, for which “there have been no effective immunotherapy-based options available,” Dana Walker, BMS vice president and global program lead of genitourinary cancers, said in a statement.

“We look forward to discussing these data with global health authorities in the coming months and have great hope that we may potentially provide these patients with a new and much needed treatment regimen,” Walker said.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at or

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