Treatment with cabozantinib induced similar quality of life results as treatment with everolimus in patients with advanced renal cell carcinoma, according to results of the randomized, open-label, international phase III METEOR trial.
David Cella, PhD
Treatment with cabozantinib (Cabometyx) induced similar quality of life (QoL) results as treatment with everolimus (Afinitor) in patients with advanced renal cell carcinoma (RCC), according to results of the randomized, open-label, international phase III METEOR trial.1
In the trial, investigators randomly assigned 658 patients with clear cell RCC to 60 mg of daily cabozantinib (n = 330) or 10 mg of daily everolimus (n = 328). By MSK criteria, approximately 46% of patients in each arm were in the favorable prognostic risk category, 41% were intermediate, and 13% were poor.
Patients in both arms completed the 19-item Functional Assessment of Cancer TherapyKidney Symptom Index (FKSI-19) and the 5-level EuroQol (EQ-5D-5L) questionnaires at baseline and throughout the study. Investigators converted severity scores from the 5 dimensions into a single population-based index value (EQ-Index) normalized across the 9 countries in the study for which index value sets were available.
Investigators also analyzed the 9-item FKSIDisease-Related Symptoms (FKSI-DRS), a subset of FKSI-19. Patients also completed a 20-cm vertical visual analog scale (EQ-VAS) scored from zero (“worst health you can imagine”) to 100 (“best health you can imagine”).
Investigators summarized data descriptively and by repeated-measures analysis; an effect size ≥0.3 was considered a clinically relevant difference.
FKSI-19 Total Score was 3.483 in the cabozantinib group versus –2.214 in the everolimus arm (effect size, –0.13). FKSI-DRS was –0.52 in the cabozantinib group versus –0.93 in the everolimus arm (effect size, 0.087). EQ-VAS was –1.32 in the cabozantinib group versus –1.27 in the everolimus group (effect size, –0.003). EQ-Index was –0.02 in both arms (effect size, –0.009).
“The METEOR trial showed that QoL declined initially and was generally maintained over time to a similar extent in both the cabozantinib and everolimus arms,” wrote first author David Cella, PhD, Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, and colleagues. “The totality of results, including progression-free survival (PFS), overall survival (OS), and objective response rate, shows that cabozantinib has a favorable clinical benefit compared with everolimus for previously treated patients with advanced RCC.”
A majority of patients in each arm had received 1 prior VEGFR tyrosine kinase inhibitor (TKI; 71%), with approximately 30% of patients having received ≥2 prior VEGFR TKIs. Use of prior VEGFR TKIs included sunitinib (Sutent; 64% in the cabozantinib arm vs 62% in the everolimus arm), pazopanib (Votrient; 44% vs 41%), axitinib (Inlyta; 16% vs 17%), and sorafenib (Nexavar; 6% vs 9%). The rates of prior cytokines, PD-1/PD-L1 agents, and bevacizumab (Avastin) between the cabozantinib and everolimus arms were similar as well, at 12% versus 16%, 5% versus 4%, and 2% versus 3%, respectively. Across the study, approximately 33% of patients had received radiotherapy and 86% of patients had undergone nephrectomy.
Investigators found no differences between the treatment arms on the basis of descriptive summaries for the FKSI-19 Total, FKSI-DRS, or for the EQ instrument over time. There were also no treatment differences on the basis of a prespecified repeated-measures model change from baseline analysis for FKSI-19 Total or FKSI-DRS. Among the 19 individual items, the only differences observed were lower scores in the cabozantinib arm for diarrhea (1.280 vs –0.326) and nausea (–0.236 vs 0.069), and lower scores in the everolimus arm for shortness of breath (0.029 vs –0.271).
Based on the overall results from the METEOR trial, cabozantinib was approved by the FDA in April 2016 for the treatment of patients with advanced RCC following prior antiangiogenic therapy. The median OS in the overall population was 21.4 months with cabozantinib versus 16.5 months with everolimus (HR, 0.66;P= .0003). The median PFS was 7.4 months versus 3.9 months, respectively (HR, 0.51; P<.0001).2