medwireNews: Combination therapy with the hypoxia-inducible factor (HIF)-2α inhibitor belzutifan and the multikinase inhibitor cabozantinib shows antitumor activity in people with metastatic clear cell renal cell carcinoma (ccRCC), phase 2 study data show.
Toni Choueiri, from the Dana-Farber Cancer Institute in Boston, Massachusetts, USA, presented the findings at the 2021 Genitourinary Cancers Symposium.
He reported that the study included 52 individuals (median age 63 years, 73% men) who were treated with oral belzutifan (previously MK-6482) at a dose of 120 mg/day and cabozantinib 60 mg/day. Of these, 54% had received one prior systemic treatment regimen, 44% had received two prior treatments, and 2% had received three.
After a median 8.9 months of follow-up, the confirmed objective response rate among the 41 patients with at least 6 months of follow-up was 22% and consisted of nine partial responses. There were also a further five (12%) unconfirmed partial responses among the 28 (68%) patients who had stable disease.
When combining the partial responses with the stable disease, the disease control rate was 90%, and Choueiri noted that 88% of patients experienced a reduction in target lesion size.
He said that the median time to response was 1.9 months, and the median response duration was not reached, with all confirmed responses ongoing at the time of data cutoff.
While stressing that the data were preliminary findings, Choueiri showed that the median progression-free survival (PFS) time was 16.8 months, while the PFS rates at 6 and 12 months were 78% and 65%, respectively. The 6- and 12-month overall survival rates were 95% and 81%, respectively.
Nearly all (98%) of the 52 participants who received at least one dose of treatment experienced a treatment-related adverse event (TRAE) of any grade and 60% experienced a grade 3 event, most commonly hypertension (23%), anemia (12%), fatigue (12%), and increased alanine aminotransferase levels (6%). Treatment-related hypoxia, which Choueiri explained is an AE of interest for belzutifan, occurred in two (4%) patients, with both events of grade 3 severity.
There were no grade 4 TRAEs or treatment-related deaths but six (12%) patients discontinued treatment for AEs relating to belzutifan and eight (15%) patients discontinued due to cabozantinib-related events.
Choueiri commented: “We believe that targeting the underlying pathology of […] clear cell RCC, targeting the transcription factor HIF-2α with belzutifan and targeting downstream with the VEGF receptor inhibitor […] cabozantinib could be an effective treatment for patients with metastatic clear cell RCC.”
He added that the study follow-up is continuing in this patient group and a second cohort of patients who have received the combination without prior systemic therapy.
Discussant David Braun, also from the Dana-Farber Cancer Institute, described the findings as “interesting and potentially exciting,” but urged caution in drawing firm conclusions as the data are immature and need further follow-up.
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2021 Genitourinary Cancers Symposium; 11–13 February