Drug targeting immune system shown to help kidney cancer patients

In the second of two late-breaking presentations of research that is predicted to change the way kidney cancer patients are treated, Professor Toni Choueiri will tell the presidential session of the 2015 European Cancer Congress, about results from the first 375 patients out of a total of 658 patients recruited to the phase III clinical METEOR trial comparing cabozantinib with everolimus, the current standard treatment for the disease. Although both drugs were able to extend the survival of patients, nivolumab did better at 25 months than the 19.6 months of evorilumus.

COMETRIQ (cabozantinib capsules) is now approved by the U.S. Food and Drug Administration for the treatment of progressive, metastatic medullary thyroid cancer (MTC). CheckMate-025 is an example of how investigators are examining approved immunotherapy drugs to determine potential impact on other tumor types.

“Although we can not speculate at this time on when nivolumab might enter the clinic, we hope that this study will quickly lead to approval of nivolumab as a standard of care therapy for these patients”, added Sharma, who is scientific director of the Immunotherapy Platform and professor in the Departments of Genitourinary Medical Oncology and Immunology at the MD Anderson Cancer Center. “Combinations with other emerging therapies, such as agents boosting the immune system, are of interest and an early stage clinical trial combining cabozantinib with immune checkpoint inhibitors has been initiated in urological cancers, including patients with kidney cancer”.

The METEOR trial randomly assigned 658 patients to cabozantinib 60 mg once daily or everolimus 10 mg once daily. That result was 4.6 months for Opdivo and 4.4 months for Afinitor.

The study included 821 patients with advanced RCC across 151 sites in 24 countries in North America, Europe, Australia, South America and Asia.

Analysts at Morgan Stanley believe Opdivo could be approved for the new use by early 2016 and the U.S. National Comprehensive Cancer Network might endorse its off-label in kidney cancer before the end of 2015. The median duration of treatment was 5.5 months with nivolumab and 3.7 months with everolimus. The survival rate depends on whether the patient is considered low risk or high risk, as well as the stage at which the cancer is diagnosed. Objective response rates were 25% with nivolumab and 5% with everolimus.

As a treatment for malignant skin cancer, nivolumab costs around £5,500 per patient per month.

For those treated with only one prior therapy, there was a 44% reduction in the risk of progression or death with cabozantinib versus everolimus (HR, 0.56; 95% CI, 0.42-0.75). Fatigue was the most common grade 3/4 adverse event, occurring in 2% of patients.

The FDA recently granted nivolumab a breakthrough therapy designation for the treatment of patients with advanced RCC, which will expedite the development and regulatory review of the anti-PD-1 agent in this setting. This corresponds to a 59% reduction in the rate of disease progression or death for patients treated with cabozantinib (HR=0.41, 95% CI 0.28-0.61). Grade 3/4 adverse events occurred in 19% of patients in the nivolumab group and 37% of patients treated with everolimus.

These results led the trial to be halted early in July 2015 when an assessment conducted by the independent Data Monitoring Committee (DMC) concluded that the study met its primary endpoint, demonstrating superior overall survival in patients receiving nivolumab.

Nivolumab is one of a new generation of antibody drugs that block “checkpoint” proteins used by many cancers to shield themselves from the immune system. “This is a new way forward”, Dr. Sharma said. The results of the METEOR study are remarkable and most likely will be practice changing. “It’s a home run for patients with the most common type of kidney cancer – therapy that promises durable responses for some”.

“This is the only phase III randomized trial to demonstrate a survival advantage in previously treated renal cell carcinoma versus standard therapy”, Sharma said during a press briefing.

PFS served as the primary endpoint. Which drug grabs a larger share of patients? The researchers learned it is effective in delaying the progression of the tumor growth.