Hand-foot syndrome and survival in patients with advanced non-small-cell lung cancer receiving anlotinib: a subgroup analysis of data from the ALTER 0303 study

Background The ALTER 0303 study showed that anlotinib can significantly improve overall survival (OS) compared with the placebo in advanced non-small-cell lung cancer (NSCLC). Hand-foot syndrome (HFS) is a common anlotinib-related adverse event. The aim of this study was to assess the association of HFS with clinical benefit. Methods A subgroup analysis of patients treated with anlotinib from the ALTER 0303 study was performed. Our analysis assessed if the appearance of anlotinib-related HFS in the first 42 days (second-cycle HFS) and at any time could produce better clinical benefits. Results In this study, 294 patients were treated with anlotinib. Of which, 129 patients had HFS at any time, and 76 patients developed HFS in the first 2 cycles. Patients who received anlotinib and developed HFS had significantly prolonged OS, progression-free survival (PFS) compared to those who did not develop HFS in the first 2 cycles (13.5 vs 8.7 months, p = 0.001; adjusted hazard ratio (HR) 0.63 (95% confidence interval [CI] 0.44–0.89), p = 0.009; 5.8 vs 4.5 months, p = 0.001; adjusted HR, 0.59 [0.43–0.81], p = 0.001). The significant OS and PFS benefits for patients with HFS versus without were seen at any time (14.5 vs 7.3 months, p = 0.000; adjusted HR, 0.50 [0.36–0.67], p = 0.000; 5.8 vs 4.2 months, p = 0.000; adjusted HR, 0.49 [0.37–0.65], p = 0.000). In addition, the grade of severity of HFS was strongly correlated with OS ( p = 0.000). Conclusion Presence of HFS may be a potential clinical marker for the treatment of NSCLC with anlotinib.