Cabozantinib Appears to be More Effective for Treating Advanced RCC Compared with Sunitinib

First-line cabozantinib (Cabometyx) provides longer quality-adjusted time without symptoms of disease or toxicity of treatment (Q-TWiST) compared with sunitinib (Sutent) in patients with advanced renal cell carcinoma (RCC), according to a post hoc analysis of the CABOSUN trial published in Cancer.¹

When using utility weightings that were relevant for patients with advanced RCC, the differences in Q-TWiST observed between cabozantinib and sunitinib that were statistically significant were of a clinically important magnitude. Specifically, the longer duration of Q-TWiST seen with cabozantinib was primarily related to a longer period of time spent without disease progression and without grade 3-4 toxicities.

“Taken together, the findings of the current study, which integrated treatment efficacy, toxicity, and patient preference, have indicated that the overall benefit of quality-adjusted survival is longer with cabozantinib than with sunitinib and may help to inform clinical decision making in the management of patients with aRCC,” the authors wrote.

Survival plots for cabozantinib and sunitinib with 650 days of follow-up were split into 3 health states, including time spent before disease progression without toxicity (TWiST), time spent before disease progression with toxicity (TOX), and time after disease recurrence or progression to death (REL). Moreover, Q-TWiST was the sum of the mean time spent in each health state, with each state weighted to reflect patient preferences (from 0 [worst] to 1 [best]) using utility scores.

Ultimately, across all utility combinations tested, Q-TWiST was longer with cabozantinib versus sunitinib (range of differences, +24 days to +137 days). Further, Q-TWiST differences that were deemed to be statistically significant (+92 days [95% CI, 5-178] to +137 days [95% CI, 60-214]) were of a clinically meaningful effect size (≥80 days), and were based on utility values that included those considered relevant for patients with advanced RCC (REL utility weight of 0.355, TOX utility weight of 0-1, and TWiST utility weight of 1).

“The results of the current analysis offer patients and their physicians a more comprehensive and personalized understanding of the impact of treatment with cabozantinib compared with sunitinib among patients with [advanced RCC] because it integrated [overall survival; OS], disease control, and toxicity together with an individual patient’s preference for each of these health states,” the authors wrote. “These findings also may offer additional insights to payers seeking to estimate the overall cost impact and management implications of treatment regimens when implemented in routine care.”

In an editorial written by Jeanny B. Aragon-Ching, MD, the clinical program director of Genitourinary Cancers within the Inova Schar Cancer Institute, and Ravi A. Madan, MD, clinical director of the Genitourinary Malignancies Branch at the National Cancer Institute, it was noted that even with a mathematical model such as the Q-TWiST metric, it remains difficult to measure the effects of treatment on the basis of a single metric.² Thus, it is their hope that research moving forward will focus on metrics which will better aid in determining which quality of life gains are most important with regard to toxicity.

“In the future, it is hoped that Q-TWiST analysis and perhaps emerging wearable technology for each phase 3 clinical trial will complement the [progression free survival; PFS] and OS data and will help physicians and patients to decide on what quality-of-life gains are meaningful in the face of the potential nontrivial existence of toxicity,” the editorial authors concluded.

References:

1. Chen RC, Choueiri TK, Feuilly M, et al. Quality-Adjusted Survival With First-Line Cabozantinib or Sunitinib for Advanced Renal Cell Carcinoma in the CABOSUN Randomized Clinical Trial (Alliance). Cancer. doi: 10.1002/cncr.33169

2. Aragon-Ching JB, Madan RA. Life Under the CABOSUN: Cabozantinib Improves Quality-Adjusted Survival in Comparison With Sunitinib. Cancer. doi: 10.1002/cncr.33168