A Phase I Study of Anlotinib Combined with PlatinumPemetrexed in Untreated Non-Squamous Non-Small Cell Lung Cancer

Abstract Background Anlotinib hydrochloride is an oral small molecule multi-target tyrosine kinase inhibitor, and it has been approved as third-line therapy for patients with advanced non-small cell lung cancer (NSCLC) in China. This dose-exploration study was designed to investigate the feasibility of anlotinib in combination with chemotherapy in patients with non-squamous NSCLC. Methods This phase I study followed a 3 + 3 dose reduction design with three dose levels of anlotinib (12mg, 10mg, 8mg). Anlotinib was given at an initial dose of 12mg with pemetrexed (500mg/m 2 ) plus cisplatin (75mg/m 2 ) or carboplatin (AUC = 5) on 21-day cycles for 4 cycles. The primary goal of the study was to identify the maximum tolerated dose (MTD) and secondary endpoints included progression free survival (PFS) and overall survival (OS). Results A total of eight participants were enrolled. DLTs were observed in two patients (pts) at anlotinib 12mg (grade 3 hand-foot syndrome and grade 3 appetite loss). No DLTs occurred at anlotinib 10mg and the MTD was 10mg. Among seven pts evaluable, four achieved confirmed partial response (PR) and three had stable disease (SD). With a median follow-up of 10.05 months, the median PFS was 7.00 months (95%CI: 2.76 to NE). Grade 3 treatment-related adverse events (TRAEs) included appetite loss (n = 2), hypertension (n = 2), thrombocytopenia (n = 1), diarrhea (n = 1) and hand-foot syndrome (n = 1). No grade 4 or grade 5 TRAEs observed during the treatment. Conclusion The feasible dose of anlotinib in combination with platinum-pemetrexed as first-line therapy was 10 mg, which was well tolerated and showed promising antitumor activity in advanced non-squamous NSCLC.