Bristol Myers Squibb’s Opdivo (Nivolumab) Under EU Review for Adjuvant Treatment of Muscle-Invasive Urothelial Carcinoma

March 29, 2021/BioValleyBIOON/-- Bristol-Myers Squibb (BMS) recently announced that the European Medicines Agency (EMA) has accepted the Class II variation application for the anti-PD-1 therapy Opdivo (generic name: nivolumab) and has initiated the centralized review procedure: to use Opdivo as an adjuvant (postoperative) treatment for patients with high-risk muscle-invasive urothelial carcinoma (MIUC) who have undergone surgical resection.

If approved, Opdivo will be the first adjuvant immunotherapy regimen for the treatment of muscle-invasive urothelial carcinoma (MIUC) in Europe. This application is based on the results of the pivotal Phase 3 CheckMate-274 trial, which is the first positive Phase 3 study evaluating an immunotherapy as adjuvant treatment for MIUC. The data demonstrated that adjuvant therapy with Opdivo significantly prolonged disease-free survival (DFS), nearly doubling it compared to placebo, regardless of patients’ PD-L1 expression levels. In this study, Opdivo was generally well tolerated, and its safety profile was consistent with previously reported studies of Opdivo in patients with solid tumors.

Patients with muscle-invasive urothelial carcinoma (MIUC) often undergo radical cystectomy as a life-saving measure, yet their risk of cancer recurrence remains approximately 50%. In the CheckMate-274 trial, patients treated with Opdivo experienced nearly twice the disease-free survival time compared to those in the placebo group. These clinically meaningful results have the potential to transform the way physicians manage MIUC, addressing the urgent need for effective and tolerable postoperative treatment options.

Dr. Dana Walker, Vice President and Head of Genitourinary Cancer Development at Bristol-Myers Squibb, stated, “Even among patients who are disease-free following radical cystectomy for muscle-invasive urothelial carcinoma, the risk of recurrence remains high, with approximately half of patients experiencing cancer recurrence. In the CheckMate-274 trial, Opdivo significantly reduced the risk of cancer recurrence or death, demonstrating its potential to address the need for safe and effective treatment options in this patient population. We look forward to collaborating with the EMA to bring the first adjuvant immunotherapy option to patients with muscle-invasive urothelial carcinoma in the European Union.”

CheckMate-274 Clinical Data (Image source: lecancer.fr)

CheckMate-274 is a randomized, double-blind, multicenter study conducted in patients with muscle-invasive urothelial carcinoma (MIUC) at high risk of recurrence following radical surgery. Depending on patient characteristics, enrolled patients may or may not have received neoadjuvant (preoperative) chemotherapy prior to surgery. In the study, 709 patients were randomized in a 1:1 ratio to receive either Opdivo or placebo for one year. The primary endpoint was assessed in all randomized patients (intent-to-treat population, ITT) andTumorDisease-free survival (DFS) in the PD-L1 (≥1%) subgroup. Key secondary endpoints include overall survival (OS), non-urothelial recurrence-free survival (NUTRFS), and disease-specific survival (DSS).

The results showed that: (1) Among all randomized patients (ITT), adjuvant Opdivo therapy nearly doubled the disease-free survival compared to placebo: the median DFS was 10.9 months in the placebo group versus 21.0 months in the Opdivo treatment group, with a significant 30% reduction in the risk of disease recurrence (HR=0.70; 98.31% CI: 0.54-0.89, p<0.001). (2) InTumorIn the subgroup of patients with PD-L1 expression ≥1%, the median DFS in the Opdivo treatment group was not reached, whereas it was 10.8 months in the placebo group (HR=0.53, 98.87% CI: 0.34-0.84, p<0.001).

Furthermore, Opdivo also demonstrated improvement in key secondary endpoints, including non-urothelial recurrence-free survival (NUTRFS), defined as the duration of survival without disease recurrence outside the bladder, ureter, or renal pelvis. Among all randomized patients, the median NUTRFS for patients in the Opdivo treatment group exceeded 2 years (24.6 months), compared with 13.7 months in the placebo group (HR=0.72, 95% CI: 0.58–0.89). InTumorIn the subgroup of patients with PD-L1 ≥1%, the median NUTRFS was not reached in the Opdivo treatment group, compared with 10.9 months in the placebo group (HR=0.54, 95% CI: 0.38-0.77).

In this study, the safety profile of Opdivo was consistent with that reported in previous studies of solid tumors. The incidence of treatment-related adverse events (TRAEs) was 77.5% in the Opdivo group and 55.5% in the placebo group, while the incidence of Grade 3 or 4 TRAEs was 17.9% and 7.2%, respectively.

Bladder Cancer (Image source: medscape.com)

Bladder cancer is the tenth most common cancer worldwide, with approximately 550,000 new cases diagnosed annually and about 200,000 deaths attributed to the disease. Urothelial carcinoma (UC) is the most common type of bladder cancer, accounting for approximately 90–95% of all cases. Muscle-invasive urothelial carcinoma (MIUC) is a form of UC that has spread into the muscle layers of the bladder, ureter, or renal pelvis. Approximately 25% of new bladder cancer cases areDiagnosisIt is a muscle-invasive disease, which has a worse prognosis compared to non-muscle-invasive urothelial carcinoma (non-MIUC).

Most cases of urothelial carcinoma (UC) are diagnosed at an early stage. The goal of early treatment for muscle-invasive urothelial carcinoma (MIUC) is to reduce the risk of disease recurrence or spread to other parts of the body. However, rates of recurrence and disease progression remain high; more than 50% of MIUC patients experience disease recurrence after radical surgery, necessitating additional postoperative treatment options. For patients whose disease recurs as metastatic cancer, the prognosis is poor, with a median overall survival of approximately 12–24 months when treated with systemic therapy.

Notably, CheckMate-274 is the first and only Phase 3 trial to demonstrate that adjuvant (postoperative) immunotherapy reduces the risk of disease recurrence in patients with muscle-invasive urothelial carcinoma (MIUC) at high risk of recurrence after radical surgery.

By shifting immunotherapy to the early stages of cancer, there is an opportunity to interrupt disease progression, reduce recurrence, and provide patients with better prognoses. To date, Opdivo-based regimens have been evaluated in four Phase 3 trials for the treatment of early-stage cancer.Clinical Trialhas demonstrated efficacy, including as adjuvant (postoperative) therapy for bladder cancer,Melanoma, esophageal/gastroesophageal junction cancer, non-small cell lung cancer.

Opdivo is a PD-(L)1 cancer immunotherapy designed to harness the body’s own immune system to fight cancer by blocking the PD-1/PD-L1 signaling pathway, thereby inducing cancer cell death, and is indicated for the treatment of various typesTumorpotential. Currently, Opdivo has become a foundational therapy for multiple types of cancer.

In China, Opdivo (Opdivo) was approved for marketing in June 2018, becoming the first approved immunotherapy in the Chinese market.Tumor(I-O) therapeutic agent. In March 2020, the National Medical Products Administration (NMPA) approved Opdivo for the treatment of patients with advanced or recurrent gastric or gastroesophageal junction adenocarcinoma who had previously received two or more systemic therapy regimens. This approval for gastric/gastroesophageal junction adenocarcinoma marks the third indication for Opdivo (Opdivo) in China, following non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN). (Bioon.com)

Original source: European Medicines Agency Validates Bristol-Myers Squibb’sapplication for Opdivo (nivolumab) as Adjuvant Treatment for Patients with Muscle-Invasive Urothelial Carcinoma