Nivolumab Sustains Survival Benefit in RCC at 3 Years

Padmanee Sharma, MD, PhD

Nivolumab (Opdivo) reduced the risk of death by 26% compared with everolimus (Afinitor) in patients with previously treated advanced renal cell carcinoma (RCC), according to 3-year follow-up data from the phase III CheckMate-025 study.

Median overall survival (OS) was 25.8 months with nivolumab compared with 19.7 months for patients assigned to everolimus (hazard ratio [HR], 0.74; 95% CI, 0.63-0.88; P = .0005). The 3-year OS rate with nivolumab was 39% versus 30% with everolimus.

Investigators presented the results at the 16th International Kidney Cancer Symposium in Miami, Florida. Bristol-Myers Squibb (BMS) announced the results in a press release, reporting that nivolumab is the first anti—PD-1 agent to demonstrate durable survival at 3 years in previously treated RCC.

“The updated results of CheckMate-025 reinforce the overall survival benefit and safety profile of Opdivo and provide further support for this therapeutic option as a standard of care for patients with previously treated advanced renal cell carcinoma,” Padmanee Sharma, MD, PhD, scientific director, Immunotherapy Platform, MD Anderson Cancer Center,” said in a press release.

CheckMate-025 is an open-label, randomized phase III study comparing nivolumab versus everolimus in patients with previously treated advanced RCC after prior antiangiogenic therapy. Patients were randomly assigned to either 3 mg/kg of IV nivolumab every 2 weeks (n = 406) or 10 mg of once daily oral everolimus (n = 397) until disease progression or unacceptable toxicity.

The primary endpoint was OS and secondary endpoints included objective response rate (ORR), progression-free survival (PFS), quality of life (QoL) and safety. Patient-reported QoL was measured using the kidney-specific, Functional Assessment of Cancer Therapy—Kidney Symptom Index–Disease Related Symptoms (FKSI-DRS) scale, and European Quality of Life (EuroQol)-5 Dimensions (EQ-5D) questionnaire.

Nivolumab demonstrated an ORR of 26% compared with 5% with everolimus. Median duration of response was 12.3 months (95% CI, 9.1-18.2) for nivolumab compared with 12 months (95% CI, 6.4-21.7) for everolimus. Median PFS was 4.2 months for nivolumab versus 4.5 months for everolimus (HR, 0.85; 95% CI, 0.73-0.99; P = .0371).

“The CheckMate -025 data reinforce Opdivo as the standard of care in previously treated renal cell carcinoma, with the 3-year data demonstrating a continued survival benefit with a greater than 6-month improvement over everolimus,” Arvin Yang, MD, PhD, development lead, melanoma and genitourinary cancers, BMS, said in a release.

“Building on the unprecedented 2-year overall survival data from this trial, these are the first 3-year overall survival for an anti—PD-1 agent in advanced RCC, showcasing our ongoing commitment to improving survival rates for people living with the most common type of kidney cancer in adults worldwide,” added Yang.

Investigators did not observe any new safety signals in this analysis—the incidence and type of treatment-related adverse events (AEs) were consistent with previous reports. Twenty-one percent of patients assigned to nivolumab experienced treatment-related grade 3/4 AEs compared with 37% in the everolimus group.

Treatment-related grade [3/4] AEs leading to discontinuation in 8% of patients in the experimental group and 13% in the everolimus group. The most common grade 3/4 AEs in the nivolumab arm were hepatic (3%) and gastrointestinal (GI; 2%). In the everolimus arm, the most common grade 3/4 AEs were pulmonary (3%), GI (2%), and skin (1%). There were no treatment-related deaths reported in the nivolumab group and 2 treatment-related deaths reported in the everolimus arm.

The FDA approved nivolumab in November 2015 as a treatment for patients with metastatic renal cell carcinoma following prior antiangiogenic therapy.

Opdivo (nivolumab) Demonstrates Superior Three-Year Survival Benefit for Patients with Previously Treated Advanced Renal Cell Carcinoma (RCC). Bristol-Myers Squibb. http://bit.ly/2iyQKlX. Accessed November 6, 2017.