Opdivo Receives FDA Approval as the First Immune Checkpoint Inhibitor for Adjuvant Treatment of High-Risk Muscle-Invasive Urothelial Carcinoma

SHANGHAI, August 25, 2021 /PRNewswire/ -- Bristol-Myers Squibb recently announced that the U.S. Food and Drug Administration (FDA) has approvedOpdivo(Nivolumab) 240 mg every 2 weeks or 480 mg every 4 weeks (intravenous) regimen for the adjuvant treatment of patients with urothelial carcinoma (UC) at high risk of recurrence following radical resection, regardless of prior neoadjuvant chemotherapy, lymph node involvement, or PD-L1 expression status. This approval is based on the results of the Phase III clinical study CheckMate-274, which aimed to evaluateOpdivoEfficacy and Safety of 240 mg (n=353) versus Placebo (n=356)^[1]。This application was reviewed by the FDA under the Real-Time Oncology Review (RTOR) pilot program. The RTOR aims to ensure that safe and effective treatments are made available to patients as early as possible.^[2]。

In this trial, receivingOpdivoThe median disease-free survival (DFS) for patients in the treatment group was nearly twice that of patients in the placebo control group (20.8 months [95% confidence interval (CI): 16.5–27.6] vs 10.8 months [95% CI: 8.3–13.9]).]）^[1]. Compared with placebo,Opdivoreduced the risk of disease recurrence or death by 30% (hazard ratio [HR] 0.7, 95% CI: 0.57-0.86; P=0.0008). In tumors expressing PD-L1>=In 1% of patients,OpdivoThe median DFS in the treatment group was not reached (95% CI: 21.2–not estimable; n=140), and the median DFS in the placebo control group was 8.4 months (95% CI: 5.6–21.2; n=142),OpdivoReduced the risk of disease recurrence or death by 45% (HR 0.55, 95% CI: 0.39-0.77; P=0.0005).

“This approval represents a significant milestone for patients who have undergone radical cystectomy or partial resection of the urinary tract. These patients urgently need new treatment options to help reduce their risk of postoperative recurrence of urothelial carcinoma,” stated Professor Matthew D. Galsky, Principal Investigator of CheckMate-274, Director of Genitourinary Oncology at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, Co-Director of the Center of Excellence in Bladder Cancer, and Associate Director for Translational Research: “Based on the safety and efficacy data from the CheckMate-274 study, and following FDA approval, nivolumab provides a novel treatment approach that effectively reduces the risk of disease recurrence or death, and is poised to become the new standard of care for this patient population.”

UseOpdivoWARNINGS AND PRECAUTIONS: Serious and fatal immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, dermatologic adverse reactions, nephritis with renal dysfunction, and other immune-mediated adverse reactions; Infusion-related reactions: Complications of allogeneic hematopoietic stem cell transplantation (HSCT); Embryo-fetal toxicity; WhenOpdivoWhen used in combination with thalidomide analogs and dexamethasone, it increases mortality in patients with multiple myeloma; therefore, use outside of controlled clinical trials is not recommended.

“Bristol-Myers Squibb’s pioneering research in the field of immunotherapy has helped transform treatment practices for numerous cancers. Moving forward, we will continue our efforts to bring more innovative breakthroughs to patients with early-stage cancer, particularly those with significant unmet medical needs,” said Adam Lenkowsky, Senior Vice President and General Manager, U.S. Cardiovascular, Immunology and Oncology at Bristol-Myers Squibb: “Opdivo is"As the world's first PD-1 inhibitor approved for adjuvant therapy, urothelial carcinoma is the third cancer type for which it has received approval in the adjuvant setting. Previously, there was no approved standard treatment regimen for these patients to prevent postoperative disease recurrence. With this approval, we bring new hope to healthcare professionals and patients with urothelial carcinoma."

The results of the CheckMate-274 study alsoOpdivoThis study provided confirmatory evidence for the FDA accelerated approval granted in February 2017 for the following patient populations: patients with locally advanced or metastatic urothelial carcinoma who experienced disease progression during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. These results ultimately supported the conversion of OPDIVO® for the aforementioned indications from FDA accelerated approval to regular approval.

AboutCheckMate -274

CheckMate-274 is a randomized, double-blind, placebo-controlled, multicenter clinical trial designed to evaluateOpdivoEfficacy as adjuvant therapy in patients at high risk of recurrence following radical resection for urothelial carcinoma (UC) of the bladder or upper urinary tract. The pathological staging criteria for defining high-risk urothelial carcinoma patients are as follows: patients who received neoadjuvant cisplatin-based chemotherapy with pathological stage ypT2–ypT4a or ypN+; or patients who did not receive neoadjuvant cisplatin-based chemotherapy and are ineligible for or refuse adjuvant cisplatin-based chemotherapy, with pathological stage pT3–pT4a or pN+.

Patients were randomly assigned toOpdivogroup (n=353) and placebo group (n=356), respectively receivedOpdivo240 mg or placebo administered via intravenous infusion over at least 30 minutes every 2 weeks until disease recurrence or unacceptable toxicity, for a maximum treatment duration of 1 year. Eligible patients are randomized in a 1:1 ratio toOpdivogroup and the placebo group, and stratified by pathological nodal status (N+ vs. N0/x [number of resected lymph nodes < 10] vs. N0 [number of resected lymph nodes>=10]), PD-L1 expression status in tumor cells (>=1% vs. <1%/indeterminate, as determined by the central laboratory using the PD-L1 IHC 28-8 pharmDx assay), and whether cisplatin neoadjuvant chemotherapy was administered (yes vs. no). The primary efficacy endpoint was investigator-assessed in all randomized patients and tumor PD-L1 expression>=DFS in 1% of patients. DFS is defined as the time to first recurrence (local urothelial, local non-urothelial, or distant metastasis) or death. Other efficacy endpoints include overall survival. FDA-approvedOpdivoThe dosage is 240 mg every 2 weeks (30-minute intravenous infusion) or 480 mg every 4 weeks (30-minute intravenous infusion), continued until disease recurrence or unacceptable toxicity, for a maximum treatment duration of 1 year.

CheckMate -274# Study Safety Results

18% of patients experienced adverse events leading to discontinuationOpdivoadverse reactions. 33% of patients delayed treatment due to adverse reactions.Opdivoof use. 30% receivedOpdivopatients experienced severe adverse reactions. ReceivedOpdivoThe most common serious adverse reactions in treated patients (>=2%) were urinary tract infections. Fatal adverse reactions occurred in 1% of patients, including pneumonia (0.6%). The most common (>=20%) adverse reactions were rash (36%), fatigue (36%), diarrhea (30%), pruritus (30%), musculoskeletal pain (28%), and urinary tract infection (22%).

About Urothelial Carcinoma

Urothelial carcinoma (UC) most commonly originates in the cells lining the inside of the bladder and is the most common type of bladder cancer among adults in the United States. Approximately 81,000 new cases of bladder cancer are diagnosed annually, the majority of which are urothelial carcinomas. In addition to the bladder, urothelial carcinoma can also occur in other parts of the urinary tract, including the ureters and renal pelvis. Although urothelial carcinoma can be diagnosed at an early stage, it is associated with high rates of recurrence and disease progression. Survival rates vary depending on the stage of the disease at diagnosis and other factors. For patients with metastatic urothelial carcinoma, the prognosis is generally poor.

References:

1.    Opdivo Prescribing Information. Opdivo U.S. Product Information. Last
updated: August 2021. Princeton, NJ: Bristol-Myers Squibb Company.

2.    U.S. Food & Drug Administration. Real-Time Oncology Review Pilot
Program. https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review-pilot-program.
Accessed August 03, 2021.