DISCUSSION
tumor, TTD, thyroid cancer
DISEASE PROGRESSION, TUMOR, ADVERSE EVENT, SECONDARY, THYROID CANCER
In this analysis, there were no significant differences in HRQoL between the lenvatinib 18 mg/day and 24 mg/day starting dose arms. Specifically, there were no statistically significant differences in LS mean change between treatment arms for both EQ‐5D and FACT‐G HRQoL scores, time to first deterioration, or time to definitive deterioration.The blinded nature of this study allowed us to address lenvatinib starting dose selection while minimizing patient and investigator bias. In real‐world practice, some clinicians initiate lenvatinib treatment at doses lower than the approved 24 mg/day starting dose in an attempt to minimize treatment‐emergent AEs (TEAEs) and optimize HRQoL; however, this may prevent patients from receiving the full efficacy benefits of lenvatinib. The Study 211 HRQoL results combined with the primary analysis suggest that use of a lower lenvatinib starting dose may compromise efficacy without improving HRQoL or safety in patients with RR‐DTC.The HRQoL data from Study 211 are particularly valuable because of the dearth of HRQoL data in patients with thyroid cancer treated with targeted therapies. An analysis that assessed studies that included HRQoL outcomes in patients with thyroid cancer reviewed 94 articles published between 2000 and 2019 and found few studies with data on HRQoL in patients with thyroid cancer treated with kinase inhibitors.In Study 211, respective compliance rates in the lenvatinib 18 mg/day and 24 mg/day starting dose arms were high at baseline (98.7%; 97.3%) and remained high through Week 56 (96.4%; 97.0%), which support the robustness of the data collected. In this HRQoL analysis, no significant differences were seen in either time to first deterioration or time to definitive deterioration; however, some potential patterns can be observed in the TTD data. TTD data are consistent with the hypothesis that time to first deterioration may reflect patients' experience of TEAEs, and time to definitive deterioration may align with disease progression. Time to dose reduction in Study 211 was shorter in the lenvatinib 24 mg starting dose arm compared with the 18 mg starting dose arm,Although some TEAEs are known to negatively impact HRQoL outcomes, it has been suggested that antitumor efficacy might have a beneficial effect on QoL (i.e., if patients have favorable outcomes with treatment, this may positively affect HRQoL). In this analysis, HRQoL was assessed in patients who had radiologic tumor responses versus those who did not. As expected, results showed that there was a trend toward longer TTD among patients who had objective radiologic responses. For time to first deterioration, the EQ‐5D VAS, EQ‐5D HUI, and the FACT‐G total score all numerically favored patients with radiologic responses. For time to definitive deterioration, the EQ‐5D HUI nominally significantly favored patients with radiologic responses, and the EQ‐5D VAS and the FACT‐G total score both numerically favored radiologic responders.The analysis of HRQoL outcomes was a secondary objective of Study 211, with no statistical hypotheses prespecified for these outcomes and, therefore, the results must be viewed as descriptive in nature, and all These results demonstrate that, contrary to common opinions among clinicians, the starting dose of lenvatinib 24 mg/day did not lead to worse HRQoL than the lower dose of lenvatinib 18 mg/day. In the primary analysis, the ORR as of Week 24 was 40.3% in the lenvatinib 18 mg/day starting dose arm versus 57.3% in the 24 mg/day starting dose arm, and the rates of TEAEs with Common Terminology Criteria for Adverse Events grade ≥3 were similar between the arms. Together with the efficacy and safety results,