According to Dr Vogelzang, the field of treatment for RCC is in significant flux right now and has changed drastically in a short period of time.
Decades ago, treatment for RCC was in the “dark ages,” he said, where clinicians were not able to offer patients anything except interleukin 2 and interferon. During this time, the median survival of patients with advanced disease was around 6 to 9 months, he said.
Slowly, as the molecular mechanisms involved in RCC became more clear, a new era began, and sorafenib, a tyrosine kinase inhibitor, was approved, followed by sunitinib and pazopanib. Shortly thereafter, came more approvals of drugs targeting another pathway active in the disease, mTOR. The advent of these drugs pushed survival to as long as 3 years or more.
Now we have what some call the “golden age,” Dr Vogelzang said. “This [comes with] the possibility that immuno-oncology drugs will cure some patients with metastatic disease. That is something that sunitinib and pazopanib were never able to accomplish.”
In April 2018, the U.S. Food and Drug Administration (FDA) approved the combination of nivolumab and ipilimumab for intermediate- or poor-risk treatment-naive advanced RCC based on the results of the CheckMate 214 trial.2 The trial randomly assigned 847 patients with intermediate- or poor-risk disease to nivolumab/ipilimumab or sunitinib. Estimated median overall survival was not reached in the combination arm compared with 25.9 months in the sunitinib arm (HR=0.63; 95% CI, 0.44-0.89; P < .0001). Overall response rate was 41.6% with the combination compared with 26.5% with sunitinib (P < .0001).
Additional excitement around immunotherapy has centered on the results of the IMmotion151 study testing atezolizumab and bevacizumab in advanced disease.3 The study randomly assigned 915 patients to atezolizumab plus bevacizumab or sunitinib alone. Patients assigned to the immunotherapy combination had a 26% reduction in risk for disease progression or death of 11.2 months compared with 7.7 months for patients assigned placebo (HR=0.74; 95% CI, 0.57-0.96; P = .02).
“This is a major revolution,” Dr Vogelzang said. “These two studies have all shown major benefits and it is likely that the other immunotherapy trial4 will show similar improvements.”
Although the “golden age” of RCC treatment may be dawning, it has not yet arrived, Dr Vogelzang said.
“The cost of the immuno-oncology drugs is phenomenally high and these drugs are not approved yet by many insurance companies,” Dr Vogelzang said. “The reality is that these drugs – sunitinib and pazopanib – are still the standard of care for the vast majority of American patients.”
In addition, sunitinib and pazopanib remain options for care in patients where immuno-oncology drugs may not have great benefit. For example, certain patients with RCC will progress shortly after beginning treatment with immunotherapy drugs, Dr Vogelzang said. In these cases, treatment with sunitinib or pazopanib is reasonable. In addition, there are patients with existing autoimmune disorders, such as rheumatoid arthritis, inflammatory bowel disease, or scleroderma, in whom immuno-oncology drugs would be contraindicated.
“In these patients, drugs like sunitinib and pazopanib become the first-line treatment of choice,” Dr Vogelzang said.
- Vogelzang NJ, Pal SK, Ghate SR, et al. Real-world economic outcomes during time on treatment among patients who initiated sunitinib or pazopanib as first targeted therapy for advanced renal cell carcinoma: a retrospective analysis of Medicare claims data. J Manag Care Spec Pharm. 2018;24:525-533.
- FDA approves nivolumab plus ipilimumab combination for intermediate or poor-risk advanced renal cell carcinoma [press release]. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm604685.htm. Silver Spring, MD: US Food and Drug Administration; Updated April 16, 2018. Accessed July 30, 2018.
- Phase III IMmotion 151 study showed Roche’s TECENTRIQ® (atezolizumab) and Avastin® (bevacizumab) reduced the risk of disease worsening or death by 26 percent in certain people with advanced kidney cancer [press release]. https://www.roche.com/media/releases/med-cor-2018-02-06.htm. Updated February 6, 2018. Accessed July 30, 2018.
- Atkins MB, Plimack ER, Puzanov I, et al. Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial [published online February 10, 2018]. Lancet Oncol. 2018;19(3):405-415. doi: 10.1016/S1470-2045(18)30081-0