Belzutifan plus cabozantinib active in advanced kidney cancer after immunotherapy
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Key takeaways:
- About 30% of patients experienced a confirmed objective response.
- One death occurred that investigators ruled as treatment related.
The combination of belzutifan and cabozantinib showed promising antitumor activity among patients with previously treated metastatic clear cell renal cell carcinoma, according to data published in The Lancet Oncology.
Belzutifan (Welireg, Merck), a first-in-class HIF-2alpha inhibitor, combined with cabozantinib (Cabometyx, Exelixis), a multikinase tyrosine kinase inhibitor, also appeared tolerable among this patient population.
“That is important as we plan next steps,” Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, told Healio. “There is an ongoing phase 3 trial with VEGF TKI+HIF2 inhibitors vs. control. There is also activity, [however] we will not be able to know how much each drug is contributing to the activity.”
Background and methodology
Limited treatment options exist for patients with advanced renal cell carcinoma following prior anti-PD-1/PD-L1-based immunotherapy; therefore, researchers sought to evaluate whether combining belzutifan and cabozantinib would confer greater antitumoral effects than either treatment as monotherapy.
Researchers conducted the single-arm phase 2 study at 10 hospitals and cancer centers across the United States. They enrolled 117 adults with locally advanced or metastatic clear cell renal cell carcinoma in two cohorts.
Patients in cohort 1 had treatment-naive disease, whereas cohort 2 consisted of patients who had previously received immunotherapy with up to two systemic treatment regimens.
Patients received 120 mg belzutifan orally once a day and 60 mg cabozantinib orally once a day until disease progression, unacceptable toxicity or patient withdrawal from the study.
Investigator-confirmed objective response served as the primary endpoint.
Choueiri and colleagues reported the results of cohort 2, which included 52 patients (median age, 63 years; 73% men; 92% white) who received at least one dose of therapy.
Results
At median follow-up of 24.6 months, 16 patients (30.8%; 95% CI, 18.7-45.1) had a confirmed objective response — one (2%) had a complete response and 15 (29%) had a partial response.
Researchers reported hypertension (27%) as the most common grade 3 to grade 4 treatment-related adverse event. Serious treatment-related adverse events occurred in 15 patients (29%). One treatment related death occurred, due to respiratory failure.
Next steps
Researchers have moved forward with additional randomized trials to further study this potential treatment option.
“We hope combining these two drugs, or largely these two mechanisms of actions, will have merits as a new combination,” Choueiri told Healio. “It remains to be determined whether this regimen can be used in what line of therapy.”
The results of patients in cohort 1 will be reported separately.
For more information:
Toni K. Choueiri, MD, can be reached at Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA 02115; email: toni_choueiri@dfci.harvard.edu.
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