Study: Four Treatment Options for Renal Cell Carcinoma Prove More Effective Than Sunitinib Monotherapy

In a presentation at the virtual Hematology/Oncology Pharmacy Association (HOPA) Annual Conference 2021, Amy M. Sion, PharmD, BCOP, reviewed 4 first line clinical trials in stage IV renal cell carcinoma, all of which compared their treatment arm to sunitinib monotherapy. In each trial, overall response rate (ORR) and median progression-free survival (PFS) in the novel treatment arm showed significant improvement over the sunitinib treatment arm.

In the CheckMate-214 trial, patients with intermediate and poor risk as measured by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model were randomized into 2 treatment arms: one using a combination of ipilimumab 1 mg/kg and nivolumab 3 mg/kg every 3 weeks for 4 cycles, followed by nivolumab monotherapy, and one using sunitinib 50 mg daily. In a 42-month follow up, the results showed a 42.1% ORR for the ipilimumab and nivolumab treatment arm compared to 26.3% for sunitinib monotherapy, and a median PFS of 11.6 months compared to 8.3 months.

“The median overall survival was still not estimable at the 42 months follow-up, but our hazard ratio is statistically significant,” Sion said. “You’ll see this with all of our IO doublet trials as well—our overall survival is taking a while to get reached because the patients are living much longer on these combination therapies.”

KEYNOTE-426, a similarly designed trial, compared patients randomly assigned to either a combination of pembrolizumab and axitinib or sunitinib monotherapy. In the initial results, published in The New England Journal of Medicine, the combination arm had an ORR of 59.3% compared to 35.7% for sunitinib, and median PFS was 15.1 months versus 11.1 months. As with CheckMate-214, median overall survival (OS) could not be evaluated at the time of analysis, although the 24-month OS reported at a follow up analysis was 74% for the pembrolizumab and axitinib group compared to 66% for patients on sunitinib monotherapy.

“When they broke their outcomes down by risk stratification, the overall survival and progression-free survival in the intermediate- to poor-risk groups favored pembrolizumab and axitinib, whereas in the favorable risk categories, both of these outcomes favor [pembrolizumab and axitinib], but were not statistically significant,” Sion said.

Slightly different in its design, the JAVELIN Renal 101 study focused on patients with tumor tissue available for programmed death-ligand 1 (PD-L1) testing and had primary endpoints of PFS and OS in patients with PD-L1 positive tumors. Patients were randomized into either the combination therapy of avelumab and axitinib, or sunitinib monotherapy. The results for patients with PD-L1 positive tumors showed an ORR of 55.2% for the combination arm compared to 25.5% for patients on sunitinib. The median PFS was 13.8 months for patients on avelumab and axitinib, and 7.2 months on sunitinib.

“This is only in patients with PD-L1 positive tumors. When we look at the overall population, the numbers are almost the same,” Sion said. “So, the authors concluded from this that PDL status does not appear to be predictive of whether or not these patients are going to respond to IO combination therapy.”

The CABOSUN trial compared the efficacy of cabozantinib monotherapy to sunitinib monotherapy, with a primary endpoint of PFS. ORR was 20% in the cabozantinib arm compared to 9% in the sunitinib arm, and median PFS was 8.6 months versus 5.3 months.

Though the trials each had similar focuses and conclusions, Sion warned against cross comparing the results of each study.

“We have a tendency to want to do that, because they look similar and because the therapies are similar, and the patients are similar,” Sion said. “However, there’s a lot of imbalances in the demographics and also in the trial design.”

REFERENCE

Amy M. Sion. Updates in Renal Cell Carcinoma. Presented at: HOPA Annual Conference 2021; April 14, 2021; Virtual.