Today’s decision makes Opdivo the first Immuno-Oncology agent approved in the European Union for the treatment of patients with this common type of bladder cancer.
“Bladder cancer has an estimated 151,000 new cases diagnosed annually in Europe, yet there have been few advancements in treatment for advanced bladder cancer during the last few decades,” said Prof. Dr. Margitta Retz, Director of the Division Uro-Oncology of the Department of Urology, Technical University Munich, Germany.
“The European Commission’s approval of nivolumab marks a significant advancement, with a notable objective response rate, and provides an important option to help patients with previously treated locally advanced unresectable or metastatic urothelial cancer.”
The approval was based on results from CheckMate -275, a Phase 2, open-label, single-arm, multicenter study evaluating Opdivo in patients with locally advanced or mUC who have disease progression during or following treatment with a platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
In this study, 270 patients received Opdivo 3 mg/kg administered intravenously every two weeks until disease progression or unacceptable toxicity.
The primary endpoint of the trial was objective response rate (ORR). Secondary endpoints included progression free survival (PFS) and overall survival (OS). In the trial, 20.0% (95% CI: 15.4, 25.3; 54/270) of patients responded to treatment with Opdivo. The percentage of patients with a complete response was 3.0% (8/270) and the percentage of patients with a partial response was 17% (46/270).
“We are pleased with the European Commission’s approval of Opdivo for patients with previously treated locally advanced unresectable or metastatic urothelial carcinoma, many of whom have been in need of an additional treatment option,” said Murdo Gordon, executive vice president and chief commercial officer, Bristol-Myers Squibb.
“With this second EU approval for Opdivo in as many months, Bristol-Myers Squibb is demonstrating our commitment to help address unmet needs for cancer patients. We intend to work closely with EU health authorities to make Opdivo available for patients with this common form of bladder cancer as soon as possible.”
Half of the overall patient population (46%) in CheckMate -275 had a tumor PD-L1 expression of ≥1% and efficacy was observed across tumor PD-L1 expressors and non-expressors.
The response rate was 25% in patients with tumor PD-L1 expression ≥1% (95% CI: 17.7, 33.6) and 15.8% (95% CI: 10.3, 22.7) in those with tumor PD-L1 expression <1%. In all treated patients, the median PFS was 2.0 months, the 12-month OS rate was 41% (95% CI: 34.8, 47.1) and the median OS was 8.6 months (95% CI: 6.1, 11.3).
Among the 270 patients who received Opdivo in CheckMate -275, 17.8% experienced a grade 3 or 4 treatment-related adverse event (AE). The most frequently reported treatment-related AEs of any grade included fatigue (16.7%), pruritis (9.3%), diarrhea (8.9%), decreased appetite (8.1%), hypothyroidism (7.8%), nausea (7.0%), asthenia (5.9%), rash (5.9%) and pyrexia (5.6%).
The most frequent treatment-related grade 3-4 AEs were fatigue (1.9%), diarrhea (1.9%), asthenia (1.5%) and rash (1.1%). Overall, 4.8% of patients discontinued therapy due to treatment-related AEs of any grade, and 3.0% discontinued therapy due to grade 3-4 treatment-related AEs. Treatment-related death occurred in four patients due to pneumonitis or cardiovascular failure.