Cabozantinib appears safe, effective across age groups in renal cell carcinoma

CHICAGO — Age does not appear to impact the efficacy of cabozantinib for the treatment of advanced renal cell carcinoma, according to a subgroup analysis of the METEOR trial presented at the ASCO Annual Meeting.

Although certain grade 3 or grade 4 adverse events occurred more frequently in older patients, these events appeared consistent with the safety profile of cabozantinib in the general population and remained manageable with dose reductions.

“The incidence of renal cell carcinoma increases with age,” with the highest incidence occurring at approximately 75 years, according to Frede Donskov, MD, DMSci, of the departments of clinical medicine and oncology at Aarhus University in Denmark, and colleagues.

The researchers examined outcomes from the METEOR trial, which compared cabozantinib with everolimus, in patients (n = 658) of three different age groups: younger than 65 years (60%), between 65 and 74 years (31%) and 75 years or older (10%). The age subgroups demonstrated comparable baseline characteristics.

Researchers randomly assigned patients 1:1 to treatment with cabozantinib (60 mg daily) or everolimus (10 mg daily). Classification occurred according to Memorial Sloan Kettering Cancer Center risk criteria and the number of prior VEGFR TKIs received.

Study endpoints included PFS, OS and objective response rate.

Individuals in the cabozantinib arm demonstrated a more favorable PFS across all age groups than patients who received everolimus (< 65 years, HR = 0.53; 95% CI, 0.41–0.68; 65-74 years, HR = 0.53; 95% CI, 0.37–0.77; and ≥ 75 years, HR = 0.38; 95% CI, 0.18–0.79). Cabozantinib conferred better ORR — as assessed by independent radiology committee — across all age groups (< 65 years, 15% vs. 5%; 65-74 years, 21% vs. 2%; and ≥ 75 years, 19% vs. 0%).

Cabozantinib improved median OS across all groups (< 65 years, 21.4 months vs. 17.1 months; 65-74 years, not reached vs. 18 months; and ≥ 75 years, 18.4 months vs. 14 months). Patients treated with cabozantinib experienced more favorable OS (< 65 years, HR = 0.72; 95% CI, 0.54-0.95; 65-74 years, HR = 0.66; 95% CI, 0.44–0.99; and ≥ 75 years, HR = 0.57; 95%, CI 0.28–1.14).

Dose reductions among older patients occurred more often with cabozantinib than with everolimus (< 65, 60% vs. 22%; ≥ 75, 85% vs. 36%).

Grade 3 or grade 4 adverse events largely aligned with the safety profiles reported in the overall population, although certain events, including fatigue and hypertension, appeared more likely among older patients.

“Treatment with cabozantinib improved PFS, ORR and OS compared with everolimus in patients with advanced renal cell carcinoma irrespective of age,” the researchers wrote. – by Julia Ernst, MS

Reference:

Donskov F, et al. Abstract 4578. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.

Disclosures: Donskov reports he receives research funding through his institution from GlaxoSmithKline, Novartis and Pfizer; and travel, accommodations and expenses from Exelixis. Please see the full study for a list of all other researchers’ relevant financial disclosures.