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European Commission: approval for Opdivo as adjuvant treatment for patients with radically resected, high-risk muscle-invasive urothelial carcinoma with tumor cell PD-L1 expression 1% or more

The European Commission ( EC ) has approved Opdivo ( Nivolumab ) for the adjuvant treatment of adults with muscle-invasive urothelial carcinoma with tumor cell PD-L1 expression 1% or more who are at a high risk of recurrence after undergoing radical resection.

In the phase 3 CheckMate -274 trial, Opdivo has demonstrated a statistically significant and clinically meaningful improvement in disease-free survival ( DFS ) compared to placebo in both all-randomized patients and in patients whose tumor cells express PD-L1 1% or more.

The EC decision is based on the results in patients with tumor cell PD-L1 expression 1% or more, which have shown a 47% reduction in the risk of disease recurrence or death with Opdivo versus placebo ( hazard ratio [ HR ] 0.53; 95% Confidence Interval [ CI ]: 0.38 to 0.75; p=0.0005 ), with median DFS not reached with Opdivo compared to 8.41 months with placebo.

Opdivo was generally well tolerated, with a safety profile that was consistent with previously reported Nivolumab studies in patients with solid tumors.

In the pooled dataset of Opdivo as monotherapy across tumor types ( n=4,122 ), with minimum follow-up ranging from 2.3 to 28 months, the most frequent ( 10% or more ) adverse reactions in patients receiving Opdivo were: fatigue ( 45% ), musculoskeletal pain ( 31% ), diarrhea ( 26% ), cough ( 24% ), rash ( 24% ), nausea ( 23% ), pruritus ( 19% ), decreased appetite ( 18% ), constipation ( 17% ), dyspnea ( 17% ), abdominal pain (16%), upper respiratory tract infection (16%), arthralgia (14%), pyrexia (14%), vomiting ( 14% ), headache ( 13% ) and oedema ( 10% ).
The majority of adverse reactions were mild to moderate ( grade 1 or 2 ).

CheckMate -274 is a phase 3 randomized, double-blind, multi-center study evaluating Opdivo compared to placebo in patients with muscle-invasive urothelial carcinoma at a high risk of recurrence after radical resection.
A total of 709 patients were randomized 1:1 to receive Opdivo 240 mg or placebo every two weeks for up to one year.
The primary endpoints of the trial were disease-free survival ( DFS ) in all randomized patients ( i.e., the intention-to-treat population ) and in the subset of patients whose tumor cells expressed PD-L1 1% or more. Key secondary endpoints included overall survival ( OS ), non-urothelial tract recurrence-free survival ( NUTRFS ) and disease-specific survival ( DSS ).

Bladder cancer is the 10th most common cancer in the world, with more than 573,000 new cases diagnosed annually.
Urothelial carcinoma, which most frequently begins in the cells that line the inside of the bladder, accounts for approximately 90% of bladder cancer cases.
In addition to the bladder, urothelial carcinoma can occur in other parts of the urinary tract, including the ureters and renal pelvis.
The majority of urothelial carcinomas are diagnosed at an early stage, but rates of recurrence and disease progression are high.
Approximately 50% of patients who undergo surgery will experience disease recurrence. For patients whose disease recurs as metastatic cancer, the prognosis is poor, with a median overall survival of approximately 12 to 14 months when treated with systemic therapy. ( Xagena )

Source: BMS, 2022