Exploration Of Associations Between Adverse Drug Reactions And Clinical Outcomes In Anlotinib Treatment Against Medullary Thyroid Carcinoma (Mtc): A Subgroup Analysis Based On The Alter01031 Trial.

e18518 Background: Anlotinib demonstrated favorable efficacy in a randomized, placebo-controlled phase 2b trial (ALTER01031, NCT02586350) for MTC which was published in 2019 ASCO annual meeting. Similar with other anti-angiogenesis drugs, hand-foot syndrome (HFS), hypertension and proteinuria were the major adverse drug reactions (ADRs) observed in this trial. We explored the association between common ADRs and the clinical outcomes with anlotinib in this subanalysis. Methods: Patients in the anlotinib group of ALTER01031 were divided into different groups according to the development of ADRs including HFS, hypertension or proteinuria. Kaplan-Meier method was used to estimate median PFS (mPFS) for patients in different groups. The mPFS for patients with or without dose reduction were also evaluated. Results: A total of 62 patients received anlotinib in ALTER 01031. HFS of any grade was observed in 39 patients with a mPFS of 28.5 months, which was longer than in those without HFS (14.0 months, P = 0.079). The hazard ratio for progression was 0.540 (95% CI 0.252, 1.158) although statistical difference was not reached. Similarly, more survival benefit was also observed in 29 and 38 patients who experienced hypertension and proteinuria, with mPFS of 28.5 months and 22.4 months respectively. While the mPFS for patients without corresponding ADRs were only 17.0 months (HR = 0.648 [95% CI 0.320, 1.314], P = 0.237) and 14.0 months (HR = 0.738 [95% CI 0.331, 1.65], P = 0.421). Median PFS had not been reached in 20 patients with dose reduction while was recorded as 17.0 months in those without (HR = 0.707 [95% CI 0.335, 1.496], P = 0.392). Conclusions: This analysis indicated a trend of greater PFS benefit for MTC patients treated with anlotinib who experienced HFS, hypertension or proteinuria although no statistical differences were observed. A possible positive association was also observed between dose reductions and better clinical outcomes. Clinical trial information: NCT02586350.