Health-related quality-of-life analyses from a multicenter, randomized, double-blind phase 2 study of patients with differentiated thyroid cancer treated with lenvatinib 18 or 24 mg/day

Abstract

Background: In the phase 2 double-blind Study 211, a starting dose of lenvatinib 18 mg/day was compared with the approved starting dose of 24 mg/day in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). Predefined criteria for noninferiority for efficacy in the 18 mg arm were not met; safety was similar in both arms. Impact of lenvatinib treatment on health-related quality-of-life (HRQoL) was a secondary endpoint of Study 211.

Methods: Patients with RR-DTC were randomly assigned to a blinded starting dose of lenvatinib 18 mg/day or 24 mg/day. HRQoL was assessed at baseline, every 8 weeks until Week 24, then every 16 weeks, and at the off-treatment visit, using the EQ-5D-3L and FACT-G instruments. Completion and compliance rates, mean change from baseline, and times to first and definitive deterioration were evaluated.

Results: Baseline EQ-5D and FACT-G scores, and overall changes from baseline, were comparable between patients in the lenvatinib 18 mg/day (n = 77) and 24 mg/day arms (n = 75). For the 18 mg versus 24 mg arms, least squares mean differences were -0.42 (95% CI -4.88, 4.03) for EQ-5D-VAS and 0.47 (95% CI -3.45, 4.39) for FACT-G total. Time to first deterioration did not significantly favor either arm; EQ-5D-VAS HR [18 mg/24 mg] 0.93 (95% CI 0.61-1.40), EQ-5D-HUI HR [18 mg/24 mg] 0.68 (95% CI 0.44-1.05), FACT-G total HR [18 mg/24 mg] 0.73 (95% CI 0.48-1.12). Time to definitive deterioration did not significantly favor either arm, though EQ-5D-VAS showed a trend in favor of the 24 mg arm (HR [18 mg/24 mg] 1.72; 95% CI 0.99-3.01); EQ-5D-HUI HR [18 mg/24 mg] was 0.96 (95% CI 0.57-1.63), FACT-G total HR [18 mg/24 mg] was 0.72 (95% CI 0.43-1.21).

Conclusions: In Study 211, HRQoL for patients in the lenvatinib 18 mg/day arm was not statistically different from that of patients in the 24 mg/day arm. These data further support the use of the approved lenvatinib starting dose of 24 mg/day in patients with RR-DTC.

Gov number: NCT02702388.

Keywords: HRQoL; dose intensity; kinase inhibitor; lenvatinib; quality of life; radioiodine-refractory differentiated thyroid cancer.

FIGURE 1

Mean scores over time for (A) EQ‐VAS, (B) FACT‐G total, and (C) FACT‐G physical well‐being functional scale. Scheduled assessments with fewer than 10% of patients still enrolled in each treatment arm are not displayed. CI, confidence interval; EQ‐VAS, EuroQol visual analog scale; FACT‐G, Functional Assessment of Cancer Therapy–General.

FIGURE 2

TTD^a in patients who received starting doses of lenvatinib 18 mg/day versus 24 mg/day. (A) Time to first deterioration. (B) Time to definitive deterioration. ^aA deterioration event for a HRQoL outcome was defined as a detrimental change in score relative to baseline that exceeded the MID threshold for decline for that score. MIDs used in this analysis were: decrease of ≥7 points (FACT‐G ¹⁹ , ²⁰ ), decrease of ≥0.08 points (HUI ²¹ ), and decrease of ≥7 points (EQ‐VAS ²¹ ). Time to first deterioration was defined as the number of weeks between randomization and the first deterioration event during the treatment period. Time to definitive deterioration was defined as the number of weeks between randomization and the earliest deterioration event during the treatment period with no subsequent recovery above the deterioration threshold. CI, confidence interval; EQ‐5D, EuroQol 5‐dimension scale; FACT‐G, Functional Assessment of Cancer Therapy–General; HUI, health utilities index; MID, minimally important difference; NE, not estimable; TTD, time to deterioration; VAS, visual analog scale.

FIGURE 3

TTD^a in radiologic responders versus nonresponders to lenvatinib. (A) Time to first deterioration. (B) Time to definitive deterioration. ^aA deterioration event for a HRQoL outcome was defined as a detrimental change in score relative to baseline that exceeded the MID threshold for decline for that score. MIDs used in this analysis were: decrease of ≥7 points (FACT‐G ¹⁹ , ²⁰ ), decrease of ≥0.08 points (HUI ²¹ ), and decrease of ≥7 points (EQ‐VAS ²¹ ). Time to first deterioration was defined as the number of weeks between randomization and the first deterioration event during the treatment period. Time to definitive deterioration was defined as the number of weeks between randomization and the earliest deterioration event during the treatment period with no subsequent recovery above the deterioration threshold. CI, confidence interval; EQ‐5D, EuroQol 5‐dimension scale; FACT‐G, Functional Assessment of Cancer Therapy–General; HUI, health utilities index; MID, minimally important difference; NE, not estimable; TTD, time to deterioration; VAS, visual analog scale.