IN A RETROSPECTIVE analysis of median overall survival from the phase III METEOR trial,1 Ignacio Duran, MD, PhD, and colleagues sought to determine whether early tumor shrinkage following therapy with cabozantinib or everolimus could be an early indicator of prognosis for patients with metastatic renal cell carcinoma. Dr. Duran is with the Hospital Universitario Marques de Valdecilla, in Santander, Spain. He presented preliminary findings from the group’s analysis at the 2019 Genitourinary Cancers Symposium in San Francisco.2
Ignacio Duran, MD, PhD
The Phase III METEOR trial was reported earlier by Toni K. Choueiri, MD, et al.1 Dr. Choueiri is Director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute in Boston.
In the study, patients with previously treated advanced renal cell carcinoma were randomly assigned 1:1 to receive either the multitargeted tyrosine kinase inhibitor (TKI) cabozantinib, or the inhibitor of mammalian target of rapamycin (mTOR) everolimus. Patients in the group receiving cabozantinib experienced greater overall survival, progression-free survival, and objective response rates than those receiving everolimus.
IN THE RETROSPECTIVE analysis of the METEOR study, Duran et al assigned all study participants (n = 658) to one of three groups based on response, namely: early tumor shrinkage of any level; tumor shrinkage of 30% or greater; or no tumor shrinkage following treatment with cabozantinib or everolimus. Patients who received cabozantinib had greater degrees of tumor shrinkage compared to those who received everolimus, the investigators noted.
“This [retrospective, phase III METEOR trial] is a preliminary analysis ... but I think this is important data.”— Ignacio Duran, MD, PhD
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Duran and colleagues sought to identify whether the degree of early tumor shrinkage was predictive of outcomes. They noted that more patients treated with cabozantinib achieved 30% or greater levels of early tumor shrinkage compared to those who were treated with everolimus (20% vs 5%); further, the degree of any early tumor shrinkage was higher in the group treated with cabozantinib (73% vs 47%).
The investigators estimated median overall survival at the first computed tomography/magnetic resonance imaging scan at 8 weeks. At a median follow-up of 28 months, median overall survival rates were not reached for those patients with 30% or greater levels of early tumor shrinkage who were treated with cabozantinib, vs 10.2 months for those treated with everolimus. For those patients with any early tumor shrinkage, median overall survival was 23.7 months vs 17.3 months (P < .05) for those treated with everolimus. Median overall survival rates were similar for patients who showed no early tumor shrinkage following treatment with cabozantinib or everolimus.
Summary of Findings
DR. DURAN NOTED there were a few interesting take-home messages from the analysis based on the data presented. Namely, cabozantinib was superior to everolimus in achieving any level of early tumor shrinkage, as well as 30% or greater levels of early tumor shrinkage. Further, early tumor shrinkage could potentially be an early indicator of prognosis for patients with metastatic renal cell carcinoma treated with cabozantinib.
The investigators concluded that “cabozantinib demonstrated a higher rate and greater magnitude of early tumor shrinkage at first post-baseline scan compared with everolimus, and early tumor shrinkage was associated with prolonged overall survival in patients treated with cabozantinib. Dr. Duran noted, “This is a preliminary analysis, and we are working on further analyses, but I think this is important data.”
DISCLOSURE: Dr. Duran reported he has received honoraria from Ipsen, Bristol-Myers Squibb, and Roche/Genentech; has served in a consulting or advisory role for Bayer, Bristol-Myers Squibb, Roche/Genentech, and MSK Oncology; received research funding (paid to his institution) from Roche/Genentech; and has been compensated for travel, accommodations, and expenses by Roche/Genentech. Dr. Choueiri has received grants and personal fees from AstraZeneca, Bristol-Myers Squibb, Eisai, Exelixis, GlaxoSmithKline, Merck, Novartis, Pfizer, Peloton, and Roche/Genentech; personal fees from Bayer, Cerulean, Corvus, Foundation Medicine, and Prometheus Laboratories; and grants from Tracon.
1. Choueiri TK, Escudier B, Powles T, et al: Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): Final results from a randomized, open-label, phase III trial. Lancet Oncol 17:917-927, 2016.
2. Duran I, Maroto P, Suárez C, et al: Analysis of overall survival based on early tumor shrinkage in the phase III METEOR study of cabozantinib versus everolimus in advanced renal cell carcinoma. Abstract 550. Presented at the 2019 Genitourinary Cancers Symposium. February 16, 2019.