JAVELIN Renal 101: Combination Therapy vs Standard of Care in Advanced RCC

Combining the immune checkpoint blocker avelumab with the tyrosine kinase inhibitor (TKI) axitinib (A + Ax) may significantly improve progression-free survival (PFS) across all prognostic risk groups and programmed death ligand 1 (PD-L1) subgroups compared with sunitinib in patients with advanced renal cell carcinoma (RCC), according to a new subgroup analysis of the JAVELIN Renal 101 trial. The results were presented at the 2019 ASCO Genitourinary Cancers Symposium.

“Will this become the standard of care? I think time will tell,” said Che-Kai Tsao, MD, an associate professor of medicine, hematology, and medical oncology at the Icahn School of Medicine and medical director of the Ruttenberg Treatment Center at The Tisch Cancer Institute at Mount Sinai Health System in New York. These findings are exciting and set the bar much higher than in the past when it comes to treating this patient population, he added.

The trial, led by Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute/Brigham and Women’s Hospital, and colleagues, included a total of 886 treatment-naïve patients who were randomized to A + Ax (median follow-up, 12.0 months) or sunitinib (median follow-up, 11.5 months).

Although sunitinib has been a standard treatment for advanced clear cell RCC, researchers found that combination therapy with A + Ax may offer significant advantages over sunitinib in several areas. Specifically, combination therapy significantly extended median PFS by more than 5 months compared with sunitinib as a first-line treatment for patients with advanced RCC, irrespective of PD-L1 expression (13.8 months vs 8.4 months).

In addition, the objective response rate (ORR) was doubled among those who received combination therapy compared with those who received sunitinib alone (51.4% vs 25.7%). The study is continuing for the other primary endpoint of overall survival. 

These new data reinforce the consistency of the PFS and ORR results across patient subgroups, including patients with favorable, intermediate, and poor prognoses, as well as those with PD-L1-positive or PDL1-negative tumors. In subgroup analyses, approximately two-thirds of patients with favorable risk (66% of patients using the Memorial Sloan Kettering Cancer Center risk model and 68% with the International Metastatic Renal Cell Carcinoma Database Consortium risk model) achieved a complete or partial response with the combination therapy.

In the combination arm, 20.8% of patients received subsequent anticancer drug therapies, compared with 39.2% in the sunitinib arm. Adverse events of grade 3 or higher during treatment (treatment-emergent adverse events [TEAEs]) occurred in 71.2% of patients in the combination arm and 71.5% in the sunitinib arm. Grade 3 or higher TEAEs that occurred in more than 5% of patients receiving the combination therapy were hypertension (25.6%), diarrhea (6.7%), increased alanine aminotransferase level (6.0%), and hand-foot syndrome (5.8%).

“No surprises on side effects turned up, which is in line with what we see with other combinations,” Tsao said in an interview with Cancer Network. “I think, overall, we are entering an age of combination therapy in kidney cancer.”