Early tumor shrinkage associated with OS benefit from cabozantinib in advanced kidney cancer

SAN FRANCISCO — Cabozantinib induced early tumor shrinkage — associated with prolonged OS — at a higher rate and to a greater degree than everolimus among patients with advanced renal cell carcinoma, according to data from the phase 3 METEOR study presented at Genitourinary Cancers Symposium.

“Early tumor shrinkage is defined as a decrease in the sum of the longest diameters of the target lesion in the first CT scan performed after initiating therapy,” Ignacio Duran, MD, PhD, of the department of medical oncology at Hospital University Virgen del Rocio Instituto de Biomedicina de Sevilla in Spain, said during his presentation. “It is also true that early tumor shrinkage has been correlated with better survival in previous works in metastatic kidney cancer.”

Earlier results from the METEOR study showed that cabozantinib (Cometriq/Cabometyx, Exelixis) improved median OS compared with everolimus (Afinitor/Zortress, Novartis; 21.4 months vs. 16.5 months; HR = 0.66).

Duran and colleagues sought to determine the impact of early tumor shrinkage on OS in the METEOR study.

The study included 658 patients with previously treated advanced renal cell carcinoma who were randomly assigned to receive cabozantinib 60 mg once daily (n = 330) or everolimus 10 mg once daily (n = 328).

The investigators stratified participants by Memorial Sloan Kettering Cancer Center risk group and number of previous vascular endothelial growth factor receptor tyrosine kinase inhibitor treatments.

Researchers assessed target lesion size by independent radiology review through CT/MRI scans at baseline, every 8 weeks for the first 12 months and every 12 weeks thereafter. They estimated median OS for three groups of patients: those with 30% or more, any or no early tumor shrinkage at first post-baseline scan, conducted at week 8.
Median follow-up was 28 months (interquartile range, 25-30).
A greater proportion of patients assigned cabozantinib had any (73.3% vs. 47.3%) or at least 30% (19.7% vs. 4.9%) early tumor shrinkage, whereas more patients assigned everolimus had no early tumor shrinkage (47.6% vs. 23.3%).

Researchers then correlated the degree of early tumor shrinkage to OS.

Among patients with any early tumor shrinkage, median OS with was 23.7 months (95% CI, 21.7-27.7) with cabozantinib vs. 17.3 months (95% CI, 15.4-20.8) with everolimus (stratified HR = 0.62; 95% CI, 0.48-0.8).

In the group of patients who achieved 30% or greater early tumor shrinkage, median OS was not reached (95% CI, 23.7-not reached) with cabozantinib vs. 10.2 months (95% CI, 3.9-not estimable) with everolimus (stratified HR = 0.45; 95% CI, 0.21-0.95).
appeared comparable between the two drugs in patients with no early tumor shrinkage (15.9 months vs. 17.4 months: HR = 0.94; 95% CI, 0.67-1.32).

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Results showed median time to objective response of 1.91 months (range, 1.6-11) with cabozantinib vs. 2.14 months (range, 1.9-9.2) with everolimus.

“Putting all these data together, I think we can say that in the phase 3 METEOR trial, cabozantinib demonstrated a greater magnitude and higher rate of early tumor shrinkage than everolimus,” Duran said. “In patients treated with cabozantinib, any early tumor shrinkage and 30% or more early tumor shrinkage were associated with prolonged OS.

“So, early tumor shrinkage at first post-baseline scan may be an early indicator of clinical benefit in patients with metastatic kidney cancer who are receiving cabozantinib treatment,” he added. “Nevertheless, this is a preliminary analysis, and further analyses are warranted to better characterize this association.” – by Jennifer Byrne
Reference:

Duran I, et al. Abstract 242769. Presented at: Genitourinary Cancers Symposium; Feb 14-16, 2019; San Francisco.

Disclosures: Duran reports honoraria from Astellas Pharma, Bristol-Myers Squibb, Ipsen, Janssen Oncology and Roche/Genentech; consultant/advisory roles with Bayer, Bristol-Myers Squibb, Janssen Oncology, MSD Oncology, Novartis, Pharmacyclics, Roche/Genentech and Seattle Genetics; institutional research funding from Astellas Pharma, AstraZeneca Spain, Janssen Oncology and Roche/Genentech; and travel/accommodations expenses from AstraZeneca Spain and Roche/Genentech. Please see the abstract for all other researchers’ relevant financial disclosures.