Cabozantinib improves outcomes in patients with advanced renal cell carcinoma

Issue: August 10, 2016

CHICAGO — Cabozantinib prolonged OS and PFS and resulted in a higher overall response rate compared with everolimus in patients with previously treated advanced renal cell carcinoma, according to final OS results of the phase 3 METEOR trial presented at the ASCO Annual Meeting.

Perspective from Charles J. Ryan, MD

“This data is intriguing as cabozantinib (Cabometyx, Exelixis) improved outcomes in the first-line setting against an active standard in the CABOSUN trial, which also met its primary endpoint recently and showed superiority over sunitinib,” Toni K. Choueiri, MD, a medical oncologist at Dana-Farber/Brigham and Women’s Cancer Center, told HemOnc Today.

Toni K. Choueiri

Cabozantinib — a tyrosine kinase inhibitor of MET, VEGF inhibitors and AXL — is the first approved therapy to demonstrate a benefit in OS, PFS and ORR in a phase 3 trial of patients with advanced renal cell carcinoma who have received prior antiangiogenic therapy.

Choueiri and colleagues randomly assigned 658 patients 1:1 to receive 60 mg of cabozantinib daily or 10 mg of everolimus (Afinitor, Novartis) daily.

A previous report showed the trial met its primary endpoint of PFS. Patients in the cabozantinib achieved a median PFS of 7.4 months compared with 3.8 months in the everolimus group.

In addition, patients in the cabozantinib group achieved higher ORR according to independent review (17% vs. 3%) and investigator review (24% vs. 4%).

Researchers conducted a secondary interim analysis for OS after a minimum follow-up of 13 months and after 320 deaths occurred. At that time, 74 (22%) patients remained on therapy in the cabozantinib arm vs. 25 (8%) patients in the everolimus arm.

Data from this analysis showed the secondary endpoint of OS also was met.

Patients in the cabozantinib arm achieved a median OS of 21.4 months compared with 16.5 months in the everolimus arm. These data equated to a 33% reduction in the risk for death (HR = 0.67; 95% CI, 0.53-0.83).

Fifty-eight percent of the cabozantinib group achieved the landmark 18-month OS compared with 47% of the everolimus group.

Cabozantinib showed an OS benefit in all prespecified subgroups — including those based on Memorial Sloan Kettering Cancer Center risk group, number and type of prior VEGFR TKIs, prior anti–PD-1/PD-L1 treatment, location and extent of tumor metastases, and tumor MET expression levels.

“The presentation focused on OS, which was extended by almost 5 months compared with everolimus,” Choueiri said. “We also presented results based on several extensive subgroup analyses, all showing that the benefit from cabozantinib over everolimus is consistent across several subgroups.”

Severe adverse events appeared consistent with the safety profile previously reported.

Next, researchers plan to investigate combination therapy using cabozantinib and nivolumab (Opdivo, Bristol-Myers Squibb), Choueiri said.

“The field is evolving and combinations with checkpoint inhibitors are of interest, particularly the first-line renal cell carcinoma setting — including cabozantinib combinations with other drugs, including nivolumab,” he added. “A current ongoing phase 1 study evaluates the combination of cabozantinib in combination with either nivolumab alone or nivolumab and ipilimumab [Yervoy, Bristol-Myers Squibb].” – by Kristie L. Kahl

Reference: Choueiri TK, et al. Abstract 4506. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.

Disclosures: Choueiri reports honoraria from National Comprehensive Cancer Network and UpToDate; consultant roles with Bayer, Bristol-Myers Squibb, Eisai, Foundation Medicine, GlaxoSmithKline, Merck, Novartis, Pfizer, Prometheus and Roche/Genentech; and research funding from AstraZeneca, Bristol-Myers Squibb, Exelixis, GlaxoSmithKline, Merck, Novartis, Peloton Therapeutics, Pfizer, Roche/Genentech and TRACON Pharma.

Perspective

Charles J. Ryan, MD

In this abstract by Choueiri and colleagues, results suggest that the median OS for the cabozantinib (Cabometyx, Exelixis) arm was 21 months vs. 16.5 months for everolimus (Afinitor, Novartis) arm a 33% reduction in the rate of death, which was statistically significant.

There are a number of other landmark data presented here that also demonstrated significance. This study verifies that cabozantinib is an active drug in kidney cancer. It is a tyrosine kinase inhibitor that differs a bit from other TKIs, because it targets MET and other kinases, and so it is a very nice addition to our armamentarium against kidney cancer. However, we do not have data comparing cabozantinib to other TKIs yet, but there are other studies underway that will be reporting the comparison of cabozantinib vs. sunitinib, for example.

Overall, this is an important positive study on the evaluation of this drug for kidney cancer and will likely become a new option for these patients.

Charles J. Ryan, MD

University of California, San Francisco

Disclosures: Ryan reports no relevant financial disclosures.