Can Immunotherapy Bypass Sequential Care in RCC?

Jason Harris
Published: Friday, Feb 02, 2018
David McDermott, MD
David McDermott, MD
Is immunotherapy the future of first-line treatment for advanced renal cell carcinoma (RCC)? The answer, according to David F. McDermott, MD, leader of the kidney cancer program at DanaFarber/Harvard Cancer Center, is “maybe.”

“Immunotherapy is already a standard of care for those who fail on a VEGF TKI [tyrosine kinase inhibitor]. With CheckMate-214, it almost certainly will be FDA approved in the frontline setting. Whether that indication will be for the intermediate- and poor-risk groups or for the all-comers, we must wait and see—but it will be standard of care in 2018, no doubt. Even if it is standard of care, it still won’t benefit every patient, and there are still some patients who may get more benefit from VEGF strategies,” he said.

McDermott outlined the potential for immunotherapy in RCC at the 2nd Annual International Congress on Immunotherapies in Cancer™, hosted by Physicians’ Education Resource®, LLC, in New York, New York, in December 2017. Despite positive clinical trial results, the role of immunotherapy in RCC remains unclear, he said. Cost of treatment is a huge concern and physicians must develop biomarkers to identify the patients most likely to benefit from particular therapies. Further, he said, physicians need to learn if combination therapy can overcome innate and acquired resistance and provide durable benefits.

To show where the field might be headed, McDermott reviewed results from the phase III CheckMate-214 trial1 evaluating PD-1/CTLA-4 blockade in kidney cancer and the 3-arm phase II IMmotion 150 trial.2

In CheckMate-214, treatment-naïve patients with advanced or metastatic clear-cell RCC were randomly assigned to 3 mg/kg nivolumab (Opdivo) and 1 mg/kg ipilimumab (Yervoy) every 3 weeks for 4 doses, followed by 3 mg/ kg nivolumab every 2 weeks (n = 425) or 50 mg daily oral sunitinib (Sutent) for 4 weeks in 6-week cycles. Patients were stratified by risk group and region, and treatment was continued until disease progression or unacceptable toxicity.

Across the full intent-to-treat population (ITT), the median PFS was not improved (12.4 vs 12.3 months; HR, 0.98; 99.1% CI, 0.79-1.23; P = .8498), results that were announced at the 2017 ESMO Congress. PFS in the intermediate- and poor-risk group was 11.6 months with the combination versus 8.4 months with sunitinib (HR, 0.82; 99.1% CI, 0.64-1.05; P = .0331). A P value of .009 was required for significance (TABLE).

 

Table. Key Findings From the Check-Mate-214 Trial1

Favorable risk patients, in contrast, had a significantly higher confirmed objective response rate (ORR) with sunitinib versus the combination arm (52% vs 29%, P = .0002), as well as a significantly longer PFS (25.1 vs 15.3 months; P <.0001).

CheckMate-214 was among the first clinical trials to show improved OS in kidney cancer. Median OS for intermediate/poor risk patients was 26 months in the sunitinib arm and not reached in the combination arm (HR, 0.68; 99.8% CI, 0.44-0.89; P <.0001).

“Why do these endpoints start to merge when you include the good-risk patients? If you look at the good-risk patients alone [n = 249], the response rate strongly favors sunitinib [52% vs 29%; P = .0002]. This is some of the best sunitinib data we’ve ever seen,” McDermott said. Median PFS for good risk patients similarly favored sunitinib at 25.1 months versus 15.3 months for the combination (HR, 2.18; 99.1% CI, 1.29-3.68; P <.0001).

“There are some patients, based on their biology, who might be better off getting a VEGF-TKI first and others who might benefit more from immune combination strategies,” he said.

He noted that the combination produced fewer grade 3/4 toxicities, which he suggested could be due to CheckMate-214 participants receiving more nivolumab and less ipilimumab compared with patients in melanoma trials. McDermott said the safety outcomes could have implications for other solid tumor types such as lung and bladder cancers.


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