Opdivo (nivolumab) in Combination with Cabometyx (cabozantinib) Demonstrates Superior Efficacy Over Sunitinib in First-Line Advanced Renal Cell Carcinoma: Phase 3 CheckMate-9ER Trial Results

February 13, 2021 /BioValleyBIOON/ -- Bristol-Myers Squibb (BMS) and its partner Exelixis held a U.S. clinicalTumorNew analysis results from the pivotal Phase 3 CheckMate-9ER trial were presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GU 2021), confirming clinical significance: in the first-line treatment of advanced renal cell carcinoma (RCC), compared with the first-line standard-of-care drug Sutent (sunitinib, a tyrosine kinase inhibitor,Pfizerdevelopment), the anti-PD-1 therapy Opdivo (brand name: Opdivo; generic name: nivolumab) in combination with the targeted anticancer drug Cabometyx (cabozantinib) constitutes“Immuno-Targeted” Regimen Demonstrates Sustained Therapeutic Benefits and Significantly Improves Quality of Life.

January 2021, United StatesFDAApproval of the Opdivo + Cabometyx regimen for first-line treatment of patients with advanced RCC. The Opdivo and Cabometyx “immunotherapy + targeted therapy” combination via the Priority Review program and Real-TimeTumorThe Real-Time Oncology Review (RTOR) pilot project has been approved for all International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk categories, providing an important new first-line treatment option for patients with previously untreated advanced or metastatic renal cell carcinoma (RCC).

This approval expands Bristol-Myers Squibb’s position in first-line advanced RCC. Previously, the dual immunotherapy regimen of Opdivo and Yervoy (ipilimumab, an anti-CTLA-4 monoclonal antibody) had been approved as the standard of care for first-line treatment of patients with intermediate- or poor-risk advanced RCC.

This approval is based on the results of the pivotal Phase III CheckMate-9ER trial. The data demonstrated that, in patients with previously untreated advanced renal cell carcinoma (RCC), the “immunotherapy + targeted therapy” regimen of Opdivo plus Cabometyx showed significant improvements across all efficacy endpoints compared with Sutent, the standard first-line care, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR).

The latest data released at this conference shows that,The median follow-up time was 2 years (23.5 months). Compared with Sutent, Opdivo + Cabometyx demonstrated significant improvements across all efficacy endpoints, including progression-free survival (PFS), objective response rate (ORR), and overall survival (OS).The incidence of treatment-related adverse events (TRAEs) leading to discontinuation was low. No new safety signals were identified during long-term follow-up.

In the overall study population: (1) For PFS, the median PFS was doubled in the Opdivo + Cabometyx group compared with the Sutent group (17.0 months vs 8.3 months; HR=0.52; 95% CI: 0.43–0.64); (2) For ORR, the rate was nearly doubled in the Opdivo + Cabometyx group compared with the Sutent group (54.8% vs 28.4%); (3) For OS, the improvement in OS was maintained in the Opdivo + Cabometyx group compared with the Sutent group, with a 34% reduction in the risk of death (HR=0.66; 95% CI: 0.50–0.87); (4) For disease control rate (DCR, including complete response [CR], partial response [PR], and stable disease [SD]), exploratory analysis showed rates of 88.2% in the Opdivo + Cabometyx group and 69.9% in the Sutent group.

(5) In terms of complete response rate (CR), the exploratory analysis showed rates of 9.3% in the Opdivo + Cabometyx group and 4.3% in the Sutent group. (5) Regarding treatment discontinuation due to TRAEs, 6.6% of patients in the Opdivo + Cabometyx group discontinued both Opdivo and Cabometyx, 9.7% discontinued Opdivo alone, and 7.2% discontinued Cabometyx alone.

In an exploratory subgroup analysis of 75 patients with sarcomatoid features (typically associated with poor prognosis), the Opdivo + Cabometyx regimen demonstrated benefit in this population: compared with Sutent, it reduced the risk of death by 64% (HR=0.36; 95% CI: 0.17–0.79) and showed superior PFS (10.3 months vs. 4.2 months) and ORR (55.9% vs. 22.0%).

In an independent analysis of the CheckMate-9ER trial, with a median follow-up of 18.1 months, patients treated with Opdivo + Cabometyx reported significant health-related quality of life benefits. Compared with Sutent, treatment with Opdivo + Cabometyx was associated with lower treatment burden, reduced risk of deterioration, and fewer disease-related symptoms. These exploratory results were measured using the Functional Assessment of Cancer Therapy–Kidney Symptom Index-19 (FKSI-19), a quality-of-life instrument specific to kidney cancer, and the EQ-5D-3L tool.

Kidney Cancer (Image source: vecteezy.com)

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, causing more than 140,000 deaths worldwide each year. The incidence of RCC in men is approximately twice that in women, with the highest rates observed in North America and Europe. Globally,DiagnosisFor patients with metastatic or advanced renal cell carcinoma, the 5-year survival rate is only 12.1%. In recent years, despite some therapeutic advances, additional treatment options are still needed to prolong survival.

The CheckMate-9ER study results clearly demonstrate that the first-line treatment of advanced or metastatic RCC patients with the Opdivo and Cabometyx “immunotherapy + targeted therapy” combination regimen yields clinically meaningful improvements in key efficacy endpoints, including progression-free survival (PFS) and overall survival (OS). Furthermore, the combination of Opdivo and Cabometyx exhibits a favorable safety profile.

The active pharmaceutical ingredient of Cabometyx is cabozantinib, a tyrosine kinase inhibitor (TKI) that exerts antitumor effects by selectively inhibiting the MET, VEGFR2, and RET signaling pathways, thereby killingTumorcells, reducing metastasis and inhibiting angiogenesis. In the United States, the European Union, Japan, and other countries and regions worldwide, Cabometyx has been approved for the treatment of patients with advanced renal cell carcinoma (RCC), as well as patients with hepatocellular carcinoma (HCC) who have previously received sorafenib treatment.

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor designed to uniquely harness the body'sAutoimmunitySystem Helps Restore Anti-TumorImmune Response. Opdivo was first approved in Japan in July 2014, becoming the world’s first approved PD-1 immunotherapy. Currently, Opdivo has become an important treatment option for various types of cancer.

In the treatment of renal cell carcinoma (RCC), the approved indications for Opdivo are: (1) for patients with advanced RCC who have previously received anti-angiogenic therapy; (2) in combination with Yervoy (ipilimumab, an anti-CTLA-4 monoclonal antibody) as first-line treatment for patients with intermediate- or poor-risk advanced RCC. (Bioon.com)

Original Source: OPDIVO (nivolumab) in Combination with CABOMETYX (cabozantinib) Shows Sustained Survival and Response Rate Benefits as First-Line Treatment for Patients with Advanced Renal Cell Carcinoma in the Phase 3 CheckMate -9ER Trial