FDA Approves Nivolumab-Based Regimen for First-Line Treatment in Adult Patients With Urothelial Carcinoma

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Patients with urothelial carcinoma who were treated with the nivolumab-based regimen had better OS and PFS compared with those who received cisplatin with gemcitabine alone.

The FDA has approved nivolumab (Opdivo; Bristol Myers Squibb) in combination with cisplatin and gemcitabine for the treatment of adult patients with unresectable or metastatic urothelial carcinoma (UC) in the first-line setting. The approval comes after results from the phase 3 CheckMate-901 trial (NCT03036098).

Image credit: Aquir | stock.adobe.com

Image credit: Aquir | stock.adobe.com

Previously, nivolumab was approved for the adjuvant treatment of adult patients with UC who are at a higher risk of recurrence following radical resection. In addition, it was approved for the treatment of adult patients with locally advanced or metastatic UC who have had disease progression either during or following platinum-containing chemotherapy or who have had disease progression within 12 months following neoadjuvant or adjuvant platinum-containing chemotherapies.

“This approval marks an important advancement in a historically difficult-to-treat setting, where there has been a need for new and differentiated first-line approaches that may offer patients a chance to live longer,” said Guru P. Sonpavde, MD, medical director of Genitourinary Oncology and the phase 1 clinical research unit and Christopher K. Glanz Chair for bladder cancer research at the AdventHealth Cancer Institute in Orlando, Florida, in a press release.

CheckMate-901 is a randomized, open-label phase 3 trial evaluating the efficacy of nivolumab in combination with cisplatin and gemcitabine followed by nivolumab monotherapy compared with cisplatin plus gemcitabine alone in patients with previously untreated unresectable or metastatic UC. The trial enrolled a total of 609 patients who were eligible for cisplatin. Patients were randomly assigned to receive 360 mg of nivolumab in combination with cisplatin plus gemcitabine every 3 weeks for up to 6 cycles followed by 480 mg of nivolumab monotherapy every 4 weeks (n=304), or cisplatin plus gemcitabine alone every 3 weeks for up to 6 cycles (n=304) until disease progression or unacceptable toxicity for up to a maximum of 2 years. The primary end points of the study were overall survival (OS) and progression-free survival (PFS).

About the Trial

Trial Name: Study of Nivolumab in Combination With Ipilimumab or Standard of Care Chemotherapy Compared to the Standard of Care Chemotherapy Alone in Treatment of Participants With Untreated Inoperable or Metastatic Urothelial Cancer (CheckMate901)

ClinicalTrials.gov ID: NCT03036098

Sponsor: Bristol-Myers Squibb

Completion Date (Estimated): June 1, 2028

The trial results indicated that individuals who received the nivolumab-based regimen had their risk of death reduced by 22% at a follow-up of 33 months, demonstrating a median OS of 21.7 months compared with cisplatin plus gemcitabine alone, which was 18.9 months (Hazard Ratio [HR] 0.78; 95% Confidence Interval [CI]: 0.63, 0.96; p = 0.0171). Additionally, patients treated with the nivolumab-based regimen also had their risk of disease progression or death reduced by approximately 28% with a median PFS of 7.9 months, whereas those treated with cisplatin plus gemcitabine alone had a median PFS of 7.6 months (HR 0.72; 95% CI: 0.59, 0.88; p = 0.0012). Further, exploratory analyses indicated that patients treated with the nivolumab-based regimen had shown stronger objective response rates, complete response rates, and partial response rates compared with cisplatin plus gemcitabine alone (57.6% vs 43.1%; 22% vs 12%; and 36% vs 31%).

“Bringing [nivolumab] to the first-line setting in UC with chemotherapy is the latest realization of our history of research and progress in immunotherapy, which has helped transform the treatment landscape for many cancers, including bladder cancer,” said Wendy Short Bartie, senior vice president and general manager, US Hematology and Oncology at Bristol Myers Squibb, in a press release. “This milestone adds a meaningful expansion to our portfolio of [nivolumab]-based treatments in genitourinary cancers, where we now have offerings in UC spanning 3 indications across stages of disease and treatment needs.”

In the CheckMate-901 trial, the most common adverse reactions reported in patients (≥20%) were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, and peripheral neuropathy. Additionally, approximately 48% of patients who were treated with nivolumab in combination with cisplatin plus gemcitabine experienced serious adverse events (AEs). The most frequent serious AEs reported were urinary tract infection (4.9%), acute kidney injury (4.3%), anemia (3%), pulmonary embolism (2.6%), sepsis (2.3%), and decreases in platelet count (2.3%). Fatal AEs were reported in 3.6% of patients who received the nivolumab-based regimen, and were a result of sepsis.

“Based on outcomes and the safety profile seen in the CheckMate-901 clinical trial, the approval of [nivolumab] in combination with cisplatin and gemcitabine has the potential to change how metastatic or unresectable UC is treated for certain patients and offers them new hope,” said Sonpavade in the press release.

Reference

Bristol Myers Squibb. U.S. Food and Drug Administration Approves Opdivo® (nivolumab), in Combination with Cisplatin and Gemcitabine, for First-Line Treatment of Adult Patients with Unresectable or Metastatic Urothelial Carcinoma. News release. March 7, 2024. Accessed March 7, 2024. https://news.bms.com/news/corporate-financial/2024/U.S.-Food-and-Drug-Administration-Approves-Opdivo--nivolumab-in-Combination-with-Cisplatin-and-Gemcitabine-for-First-Line-Treatment-of-Adult-Patients-with-Unresectable-or-Metastatic-Urothelial-Carcinoma/default.aspx

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