Cabozantinib improves quality-adjusted survival in advanced RCC
medwireNews: Treatment with cabozantinib gives patients with advanced renal cell carcinoma (RCC) significantly more time without disease progression and toxicity relative to treatment with sunitinib, CABOSUN trial data show.
Darren Feldman (Memorial Sloan Kettering Cancer Center, New York, USA) and colleagues say their findings “offer patients and their physicians a more comprehensive and personalized understanding of the impact of treatment with cabozantinib compared with sunitinib.”
The phase 2 CABOSUN trial previously showed that cabozantinib significantly delays disease progression versus sunitinib in treatment-naïve patients with advanced RCC. In the current post-hoc analysis, the researchers used the Quality‐adjusted Time Without Symptoms of disease or Toxicity of treatment (Q-TWiST) method to measure quality-adjusted survival in the 157 participants.
The authors explain in Cancer that Q-TWiST incorporates three health states that are each weighted with utility scores from 0 to 1 to reflect patient preferences for each state. These include time spent before disease progression without toxicity (TWiST, with toxicity defined as a grade 3 or 4 adverse event), time spent before disease progression with toxicity (TOX), and time after relapse (REL).
The team found that, across all TOX and REL utility weighting combinations (scored in 0.25-point increments), cabozantinib was associated with a longer mean time spent without progression or toxicity versus sunitinib. The difference ranged from 137 additional quality-adjusted days when TOX and REL both carried utility weights of 0 points to 24 days when the utility weights were 1. In all scenarios, TWiST carried a utility weight of 1 as this would be the optimal health state.
The differences were statistically significant and clinically meaningful (≥80 days) when the utility values were 0 or 0.25 points for REL, any value for TOX, and 1 point for TWiST, ranging from 103 to 137 days.
“This finding can be interpreted to indicate that a patient who places maximal importance on avoiding disease recurrence (ie, REL utility weighting of 0) without regard for toxicity (ie, TOX utility weighting of 0-1) can expect to spend a mean of up to 137 additional quality-adjusted days (Q-TWiST) with first-line cabozantinib compared with sunitinib,” Feldman et al remark.
They conclude that their findings “may help to inform clinical decision making” and may also “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 accompanying editorial, Jeanny Aragon-Ching (Inova Schar Cancer Institute, Fairfax, Virginia, USA) and Ravi Madan (National Cancer Institute, Bethesda, Maryland, USA) say that although the analyses have shown statistical significance, they are limited by the fact that duration of grade 3 or 4 toxicity and the impact of lower grade toxicity are not taken into account.
For example, lower grade toxicity such as fatigue “can alter quality of life but may not be heavily considered in the toxicity measure,” they write.
The editorialists also say: “Although the comparison of 2 VEGF inhibitors is important, a more ideal comparison would involve checkpoint inhibitor therapy such as nivolumab and ipilimumab or pembrolizumab or avelumab compared to cabozantinib.”
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