On May 29, 2024 Bristol Myers Squibb (NYSE: BMY) reported that the European Commission (EC) has approved Opdivo (nivolumab) in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma (UC) (Press release, Bristol-Myers Squibb, MAY 29, 2024, View Source [SID1234643780]). With this approval, Opdivo in combination with cisplatin and gemcitabine becomes the first concurrent immunotherapy-chemotherapy approved for the treatment of adult patients with unresectable or metastatic UC in the first-line setting in the European Union.

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"With today’s approval by the EC, we’re pleased to be able to offer Opdivo concurrently with chemotherapy to eligible patients with unresectable or metastatic UC," said Dana Walker, M.D., M.S.C.E., vice president and global program lead, gastrointestinal and genitourinary cancers, Bristol Myers Squibb. "This is a major step forward for this patient population and reinforces our goal of advancing and delivering new options to patients with difficult-to-treat cancers. We extend our sincerest gratitude to the patients, their families, investigators and staff who contributed to this important research."

The EC’s decision is based on results from the CheckMate -901 trial studying Opdivo in combination with cisplatin and gemcitabine, which were presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023. In CheckMate -901, Opdivo in combination with cisplatin and gemcitabine followed by Opdivo monotherapy demonstrated statistically significant and clinically meaningful improvements in the primary efficacy endpoints of overall survival (OS) and progression-free survival (PFS) compared to chemotherapy alone, as assessed by Blinded Independent Central Review (BICR). The safety profile was consistent with the known safety profiles of the individual components of the regimen. No new safety concerns were identified.

"In the CheckMate -901 trial, the combination of Opdivo with cisplatin and gemcitabine improved overall survival, reduced the risk of disease progression or death by 28% versus chemo alone, and demonstrated deep and durable responses versus chemo alone," said Michiel Van der Heijden, M.D, Ph.D., medical oncologist and research group leader, Netherlands Cancer Institute. "These findings are significant and reinforce that concurrent Opdivo and chemotherapy should be considered as a new standard of care for the first line treatment of eligible patients with this difficult-to-treat cancer."

This approval by the EC for Opdivo in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with unresectable or metastatic UC is valid in all 27 member states of the EU, as well as Iceland, Liechtenstein and Norway.

This approval of Opdivo in combination with cisplatin and gemcitabine based on results of the CheckMate -901 trial, further supports the EU’s previous approval of Opdivo for the adjuvant treatment of adults with muscle-invasive urothelial carcinoma with tumor cell PD-L1 expression ≥1% who are at a high risk of recurrence after undergoing radical resection. In addition to this approved indication in UC, Opdivo-based options are also approved for treatment of 10 different cancer types in the EU including: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric, gastroesophageal junction (GEJ) or esophageal adenocarcinoma (EAC), esophageal or gastroesophageal junction (GEJ) cancer, colorectal cancer, mesothelioma, renal cell carcinoma, esophageal squamous cell carcinoma (ESCC) and squamous cell cancer of the head and neck.

CheckMate -901 Efficacy and Safety Results

With a median follow up of approximately 33 months of the CheckMate -901 trial, results showed:

OS (overall survival; primary endpoint): Opdivo in combination with cisplatin and gemcitabine reduced the risk of death in patients by 22%, demonstrating a median OS of 21.7 months versus 18.9 months with cisplatin-gemcitabine alone (HR (hazard ratio): 0.78; 95% CI (confidence interval): 0.63, 0.96; p=0.0171).
PFS (progression-free survival; primary endpoint): Risk of disease progression or death reduced by 28%, with a median PFS of 7.9 months compared to 7.6 months with cisplatin-gemcitabine alone (HR 0.72; 95% CI: 0.59, 0.88; p=0.0012).
ORR (overall response rate; secondary endpoint): Opdivo in combination with cisplatin and gemcitabine resulted in an ORR of 57.6% (n=175) (95% CI: 51.8, 63.2) versus 43.1% (n=131) (95% CI: 37.5, 48.9) with cisplatin-gemcitabine alone.
CR (complete response) rate and PR (partial response) rate (secondary endpoints): The CR rate and PR rate seen in patients treated with Opdivo in combination with cisplatin and gemcitabine was 22% (n=66) and 36% (n=109), respectively, versus 12% (n=36) and 31% (n=95) with cisplatin-gemcitabine alone.
About CheckMate -901

CheckMate -901 is a Phase 3, randomized, open-label trial evaluating Opdivo in combination with Yervoy (ipilimumab) or Opdivo in combination with cisplatin and gemcitabine followed by Opdivo monotherapy compared to standard-of-care chemotherapy alone, in patients with untreated, unresectable or metastatic urothelial cancer.

In CheckMate -901, evaluating Opdivo with cisplatin and gemcitabine vs. standard-of-care chemotherapy alone, a total of 608 patients eligible for cisplatin-based chemotherapy were randomized to receive either Opdivo 360 mg in combination with cisplatin and gemcitabine every three weeks for up to six cycles followed by 480 mg/Q4 Opdivo monotherapy every 4 weeks until disease progression or death up to a maximum of two years, or cisplatin-gemcitabine alone every three weeks for up to six cycles. The primary endpoints of this study are overall survival (OS) and progression-free survival (PFS).

The OS and PFS outcomes for patients eligible for cisplatin-based chemotherapy are based on the final efficacy analyses of these endpoints.

The CheckMate -901 primary study, evaluating Opdivo plus Yervoy vs. standard-of-care cisplatin- or carboplatin-based chemotherapy in patients with untreated, unresectable or metastatic urothelial carcinoma remains ongoing.

Select Safety Profile from CheckMate -901

Serious adverse reactions occurred in 48% of patients receiving Opdivo with chemotherapy.1 The most frequent serious adverse reactions reported in ≥2% of patients who received Opdivo with chemotherapy were urinary tract infection (4.9%), acute kidney injury (4.3%), anemia (3%), pulmonary embolism (2.6%), sepsis (2.3%), and platelet count decreased (2.3%).1 The most common adverse reactions (reported in ≥20% of patients) were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, and peripheral neuropathy.1 Fatal adverse reactions occurred in 3.6% patients who received Opdivo with chemotherapy; these included sepsis (1%).1 Opdivo and/or chemotherapy were discontinued in 30% of patients and were delayed in 67% of patients for an adverse reaction.

About Urothelial Carcinoma

Bladder cancer is the ninth most common cancer in the world, with more than 600,000 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 radical surgery will experience disease recurrence, especially within the first two to three years after surgical removal of the bladder or kidney. 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.