Cabo inhibits VEGFR2, MET, and AXL. In the phase 3 METEOR study, cabo improved OS (median 21.4 vs. 16.5 months; HR, 0.66; 95% CI, 0.53–0.83), progression-free survival and objective response rate compared with eve in patients with previously treated advanced RCC. Retrospective studies have shown that early tumor shrinkage (eTS), based on target lesion reduction from baseline to first post-baseline scan, has predictive value for targeted therapies in RCC. The goal of this study was to evaluate the impact of eTS on OS in the METEOR study.
Dr. Duran then summarized the study design. 658 pts were randomized 1:1 to receive cabo (60 mg qd) or eve (10 mg qd), stratified by MSKCC risk group and number of prior VEGFR TKIs. Target lesion size was assessed by independent radiology review using CT/MRI scans at baseline, every 8 weeks for the first 12 months and every 12 weeks thereafter. Median OS was estimated for patients with ≥30% eTS, any eTS or no eTS at first post-baseline scan (week 8);
Dr. Duran then highlighted the results of the METEOR study. Median follow-up was 28 months (IQR 25, 30). Median (range) time to objective response was 1.91 (1.6, 11.0) months with cabo and 2.14 (1.9, 9.2) months with eve, and corresponded to the time to the first post-baseline scan. A greater proportion of pts had ≥30% eTS with cabo (20%) than with eve (5%), and the rate of any eTS was higher in the cabo arm (73%) than with eve (47%). Median OS with cabo vs. eve for pts with ≥30% eTS was not reached (NR; 95% CI, 23.7–NR) vs. 10.2 months (95% CI, 3.9–NE), respectively (stratified HR, 0.45; 95% CI, 0.21–0.95; p<0.05). Median OS with cabo vs eve for patients with any eTS was 23.7 (95% CI, 21.7–27.7) vs 17.3 months (95% CI, 15.4–20.8), respectively; (stratified HR, 0.62; 95% CI, 0.48–0.80; p<0.05). OS was similar for cabo and eve for pts with no eTS.
Dr. Duran concluded his talk with a summary from the study showing that Cabo demonstrated a higher rate and greater magnitude of eTS at first post-baseline scan compared with eve. In patients treated with cabo, any eTS and ≥30% eTS were associated with prolonged OS in patients treated with cabo. eTS at first post-baseline scan may be an early indicator of clinical benefit in patients with mRCC who are receiving cabo treatment. Dr. Duran stressed that further analyses are warranted to better characterize this association.
Presented by: Ignacio Duran, MD, PhD, Princess Margaret Cancer Centre, University of Toronto
Written by: Abhishek Srivastava, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Fox Chase Cancer Center, Philadelphia, PA at the Annual ASCO GU meeting 2019, San Francisco, CA, Twitter: @shekabhishek at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA