Effect of second-line cabozantinib on health states for patients with advanced hepatocellular carcinoma (aHCC) after sorafenib: QTWiST analysis from the CELESTIAL study

Current strategies for the treatment of intermediate and advanced hepatocellular carcinoma

“…Similar to the other TKIs, grade 3/4 side effects occurred in 68% of patients and predominantly involved hand-foot syndrome, hypertension, transaminase elevation and fatigue. In order to assess the impact of cabozantinib on QoL, a post-hoc analysis compared patient experience of three discrete health states: time with grade 3/4 toxicity before progression (TOX), time without grade 3/4 toxicity before progression (TWiST) and survival time after progression (REL) [44]. Despite an increase in days with grade 3/4 toxicity before progression, patients treated with cabozantinib spent significantly more time without disease symptoms and toxicity than those receiving placebo.…”

Navigating the new landscape of second‐line treatment in advanced hepatocellular carcinoma

“…An overview of product characteristics is provided in Table 1. Pivotal clinical trial data are provided in Tables 2 37,49,61,69,71,72 and 3, 37,49,59,61,69,71,72 covering trial design and efficacy outcomes, and safety/tolerability and health-related quality of life (HRQoL) respectively.…”

“…With continued cabozantinib treatment, health utility increased 58 . A retrospective analysis of data from CELESTIAL found that patients receiving cabozantinib after sorafenib spent significantly more time without disease symptoms and toxicity than those receiving placebo, despite an increase in days with grade 3/4 toxicity before progression 59 …”

Which choice of therapy when many are available? Current systemic therapies for advanced hepatocellular carcinoma

“…Importantly, for HCC patients undergoing two lines of treatment, the median overall survival (OS) now exceeds 20 months, and a delayed time to clinical deterioration was reported when lenvatinib or ramucirumab was compared to sorafenib or placebo, respectively. Significant gains in terms of quality‐adjusted life‐years and time without symptoms and toxicity were also observed after treatment with cabozantinib …”

“…Significant gains in terms of quality-adjusted life-years and time without symptoms and toxicity were also observed after treatment with cabozantinib. 13,14 In the US, two immune checkpoint inhibitors (ICI), namely, nivolumab and pembrolizumab, have been approved by the FDA in a second-line context on the basis of the CheckMate 040 15 and Keynote-224 16 Provided that patients must always meet essential eligibility criteria such as a preserved liver function (ie, Child-Pugh score A) and good clinical conditions, these drugs cannot be used interchangeably. While head-to-head comparisons do not exist (except for lenvatinib and sorafenib, which were compared in the frame of a noninferiority trial), 7 safety profiles and specific criteria that drew the framework of their development in the respective pivotal trials might better inform the clinicians' decisions.…”