Cabozantinib was active with no new safety signals in second-line advanced RCC after treatment with frontline checkpoint inhibitor–based therapy.
Second-line cabozantinib (Cabometyx) monotherapy was safe and produced responses in patients with advanced renal cell carcinoma (RCC) who received frontline checkpoint inhibitor–based combinations, supporting the continued use of the agent in this setting, according to findings from the phase 2 CaboPoint study (NCT03945773) published in European Urology.1
At a median follow-up of 19.3 months (IQR, 10.9-26.3), patients in cohort A (n = 79) who received second-line cabozantinib experienced an overall response rate (ORR) per independent central review (ICR) of 40.5% (95% CI, 29.6%-52.1%). In cohort B (n = 40), the ORR was 27.5% (95% CI, 14.6%-43.9%); 2.7% of patients achieved a complete response. The disease control rates (DCRs) in the respective cohorts were 84.8% (95% CI, 75.0%-91.9%) and 82.5% (95% CI, 67.2%-92.7%).
“CaboPoint is the first study of pure second-line cabozantinib after first-line [checkpoint inhibitor]–based combinations, providing a benchmark for future second-line advanced RCC studies,” Laurence Albiges, MD, PhD, a medical oncologist in the Department of Medical Oncology at Institut Gustave Roussy in Villejuif, France, and her coauthors wrote in the publication.
CaboPoint was a European, prospective, multicenter, open-label study that examined second-line cabozantinib in adult patients with advanced RCC following prior treatment with ipilimumab (Yervoy) plus nivolumab (Opdivo) or checkpoint inhibitor therapy plus VEGF therapy. Patients were also required to have experienced radiographic disease progression following frontline therapy, at least 1 target lesion by RECIST 1.1 criteria per investigator assessment, an ECOG performance status of 0 or 1, and adequate organ and bone marrow function within 15 days before baseline.2 Those with treated brain metastases were eligible for the study if the metastases had been shown to be stable per investigator assessment.
All patients received oral cabozantinib at 60 mg per day.1 A dose reduction to 40 mg per day or 20 mg per day was permitted to manage toxicity. Therapy continued until disease progression, unacceptable toxicity, patient withdrawal, or the conclusion of the study, whichever occurred first.
Key Takeaways From the Phase 2 CaboPoint Trial
The primary end point was ORR per RECIST 1.1 criteria per ICR in cohort A. Secondary end points included ORR per ICR in cohort B, investigator-assessed ORR, progression-free survival, overall survival (OS), time to response, duration of response (DOR), DCR, quality of life, and safety.
At baseline, the mean age in the overall population (n = 127) was 64.2 years (SD, 9.3). Most patients were male (75.6%), had an ECOG performance status of 0 (60.6%), had intermediate-risk disease per International Metastatic RCC Database Consortium criteria (68.0%), had metastatic disease (61.6%), and had metastatic sites on the lungs at the initiation of treatment with cabozantinib (70.6%). The median treatment duration was 6.4 months (IQR, 2.5-12.4).
Additional findings from CaboPoint showed that the investigator-assessed ORRs in cohorts A and B were 49.4% (95% CI, 38.4%-60.5%) and 33.3% (95% CI, 19.6%-49.5%), respectively. The median PFS by ICR was 10.9 months (95% CI, 8.2-14.2) and 8.3 months (95% CI, 5.6-11.1), respectively. The median OS was 24.3 months (95% CI, 18.5-31.8) and 24.1 months (95% CI, 17.1-not calculable [NC]), respectively. The median DOR by ICR was NC (95% CI, 11.6-NC) and 8.3 months (95% CI, 5.6-NC), respectively.
In terms of safety, most patients (99.2%) in the overall cohort experienced any-grade treatment-emergent adverse effects (TEAEs); the study authors noted that most TEAEs were mild to moderate in terms of severity. Grade 3 or 4 TEAEs occurred in 75.6% of patients, including 83.5% of patients in the safety population of cohort A (n = 85) and 59.5% of patients in the safety population of cohort B (n = 42).
The most common any-grade TEAEs that were reported in at least 15% of patients in cohort A included diarrhea (71.8%), hypertension (50.6%), and decreased appetite (48.2%). In cohort B, the most common any-grade TEAEs that occurred in at least 15% of patients included diarrhea (76.2%), decreased appetite (54.8%), hypertension (47.6%), and stomatitis (47.6%). No deaths due to TEAEs occurred in either cohort A or B and treatment-related serious TEAEs occurred in 29.4% and 16.7% of patients in the respective cohorts.
“No new safety signals were reported. Our findings support the continued use of [second-line] cabozantinib monotherapy in patients whose disease progresses on [first-line checkpoint inhibitor]–based therapies and serves as a benchmark for future [second-line] trials,” Albiges and her coauthors wrote in their conclusion.
