With this approval, Opdivo positions itself to compete with Merck’s immune checkpoint inhibitor (ICI) Keytruda in combination with Astellas and Pfizer’s Padcev, a nectin-4-directed antibody-drug conjugate (ADC).
The Keytruda/Padcev combination was granted FDA approval in December 2023 as a first-line treatment for mUC and remains a ‘formidable’ rival to Opdivo in the mUC space, argues data and analytics firm GlobalData.
Opdivo approval is currently based on the phase 3 in which the combination of Opdivo with chemotherapy met the primary endpoints of overall survival (OS) and progression-free survival (PFS) compared to cisplatin and gemcitabine alone.
The trial results demonstrated a ‘potent efficacy’ in adding Opdivo to the treatment regimen, with an improved median OS of 21.7 months in the Opdivo cohort, compared to 18.9 months in individuals with platinum-based chemotherapy.
In addition, a 28% reduced risk of disease progression or death was observed, with a median PFS of 7.9 months in the Opdivo cohort versus 7.6 months in the comparator group.
Jasminemay Barcelon, oncology and hematology analyst at GlobalData, said: “The approval of Opdivo contains a chemotherapy requirement that restricts the patient population to those who are cisplatin-eligible.
“The Keytruda/Padcev combination was initially approved for the first-line treatment of cisplatin-ineligible mUC patients. However, the recent approval expanded its label to first-line treatment of mUC patients regardless of cisplatin eligibility, allowing for a larger patient share than Opdivo.”
The phase 3 EV-302 trial data that contributed to the approval of the Keytruda/Padcev combination demonstrated an median OS of 31.5 months versus 16.1 months in the other arm, 9.8 months longer than the median OS in the Opdivo trial.
Therefore, the ICI and ADC combination may become a physician’s first treatment choice in this setting, GlobalData adds.
However, aside from patient eligibility, cost-effectiveness also could play a role in deciding between the two regimens.
As ADCs are notoriously costly, the combination of Opdivo with a relatively inexpensive platinum-based chemotherapy regimen with similar efficacy may be a better alternative.
Barcelon concludes: “Platinum-based chemotherapy is the standard of care for the first-line treatment of mUC. However, there are limited treatment options that improve survival after treatment with a platinum-based therapy.
"Despite competition in the mUC space, this approval of a concurrent immunotherapy-chemotherapy combination expands the treatment options for mUC and is a significant step towards integrating immuno-oncology agents with traditional chemotherapy approaches.”