Anlotinib in radioiodine-refractory differentiated thyroid carcinoma: A subanalysis based on ALTER01032 study for patients with poor baseline characteristics.

Abstract

6022 Background: Anlotinib (anlo), a multikinase inhibitor, has demonstrated a significant survival benefit in treating locally advanced or metastatic radioiodine-refractory differentiated thyroid carcinoma (RAIR-DTC) with a nearly 4 folds prolongation in median progression-free survival (mPFS) (HR = 0.21, p < 0.0001) compared with placebo in a randomized, placebo-controlled phase 2 study (ALTER01032, NCT02586337). Older age, bone metastasis, structural progression within a short time are generally indicated as negative prognostic factors for thyroid cancer. This subanalysis explored the outcomes of patients (pts) enrolled in ALTER01032 study with these poor baseline characteristics. Methods: 113 pts were enrolled, 76 in anlo arm and 37 in placbo arm. The primary endpoint is PFS. Pts with older age (≥ 55), bone metastasis or radiographic documented disease progression within 3 months (mo) before enrollment were selected. The PFS and overall survival (OS) for these pts were estimated and compared. Since 64.9% pts in placebo arm received crossover treatment with open label anlo after progression while only 3 pts in anlo arm received post-study treatment, the penitential bias for OS from imbalance of subsequent treatment was adjusted by a two-stage estimation method. Results: The results of subanalysis were summarized in the table below. Pts with poor baseline characteristics showed higher risk of progression and death. Significant PFS prolongation was shown across all subgroups in pts received anlo compared with their counterparts who received placebo ( P < 0.05). In pts with bone metastasis or structural progression within 3 mo, anlo treatment achieved significant OS benefit ( P < 0.05). Also, in older pts, a trend of OS improvement was observed (HR = 0.85 (95% CI 0.37, 1.97)). Most pts in placebo arm received crossover anlo. After adjustment, a near-significant decrease of death risk was observed in older pts received anlo compared with those received placebo (HR = 0.48 (95% CI 0.20, 1.13)). Conclusions: This subanalysis showed anlo effectively improved both PFS and OS of pts with RAIR-DTC who have poor baseline characteristics above. Interestingly, although most pts in placebo arm received crossover anlo, they still have higher risk of death, indicating the importance of earlier treatment for these pts. Clinical trial information: NCT02586337. [Table: see text]