Combination Immunotherapy Use in Metastatic Kidney Cancer

Different combinations of immunotherapy with chemotherapy are helping patients with renal cell carcinoma live longer.

Patients with metastatic renal cell carcinoma are experiencing better response and survival rates following combination therapy upfront compared with a single medication, according to Dr. Primo Lara Jr, director of UC Davis Comprehensive Cancer Center in Sacramento, California.

Several clinical trials have demonstrated these benefits in recent years. For instance, a phase 3 trial that examined Opdivo (nivolumab) combined with Yervoy (ipilimumab) — both types of immunotherapy — showed an overall survival rate of 75% at 18 months in intermediate- and poor-risk patients with previously untreated advanced or metastatic renal cell carcinoma compared with 60% in patients who received Sutent (sunitinib) alone. In addition, median progression-free survival, meaning their disease didn’t worsen or lead to death, was 11.6 months with the combination versus 8.4 months with Sutent. The overall response rate was 42% versus 27%, respectively.

Based on data from the phase 3 JAVELIN Renal 101 trial, the Food and Drug Administration (FDA) approved Bavencio (avelumab), another type of immunotherapy medication, in combination with Inlyta (axitinib) for patients with advanced disease. The combination showed a 31% reduction in the risk of disease progression or death versus Sutent in a population of patients regardless of PD-L1 expression. The expression of this protein is typically associated with poor prognosis in patients with renal cell carcinoma.

In addition, the immunotherapy drug Tecentriq (atezolizumb) has shown hope when combined with Avastin (bevacizumab) in patients with metastatic renal cell carcinoma who had never been treated before. In the IMmotion151 trial that included more than 360 patients who were PD-L1 positive, the median progression-free survival was 11.2 months compared with 7.7 months with Sutent.

Lastly, Lara explained that Keytruda (pembrolizumab) plus Inlyta is also a key combination for renal cell carcinoma and was approved by the FDA in April 2019. The phase 3 KEYNOTE-426 trial examined the combination in patients with newly diagnosed or recurrent stage 4 clear-cell disease. Compared with Sutent, the Keytruda/Inlyta combination showed a 47% reduction in the risk of death. The overall response rate was 59.3% with the combination versus 35.7% with Sutent.

More than 73,000 people in the United States will receive a kidney cancer diagnosis this year. The disease, which typically affects older people, is twice as common in men than women. Clear cell disease represents approximately 75% of renal cancers, according to the National Institutes of Health. Non-clear cell disease is a mixture of multiple types of tumors originating in the kidney with distinct molecular and genetic characteristics.

Although the use of combinations has shifted the approach in treating renal cell carcinoma, Lara explained that Sutent alone remains “king … for now” in the treatment of patients with non-clear cell disease. Researchers are moving efforts to explore new options for patients whose disease becomes resistant to these approaches, Lara said.