151 A RANDOMIZED,OPEN CLINICAL TRIAL TO COMPARE THE EFFICACY AND SAFETY OF ANLOTINIB PLUS IRINOTECAN VERSUS IRINOTECAN IN PATIENTS WITH ESCC

The benefit of systemic treatment in esophageal squamous cell carcinoma (ESCC) which has progressed after chemotherapy is still uncertain. Anlotinib (AL3818) is a novel multi-target TKI, inhibiting tumor angiogenesis and proliferation. A phase II trial (NCT02649361) has demonstrated that anlotinib has a durable antitumor activity with a manageable adverse event profile in refractory metastatic ESCC. This study (NCT03387904) aimed at comparing the effects and safety of Anlotinib Plus Irinotecan versus Irinotecan in patients with ESCC. Methods We conducted a prospective randomized, multicenter, phase II trial to compare the efficacy of Anlotinib Plus Irinotecan with Irinotecan in recurrent ESCC patients who had resistance to platinum or taxane-based chemotherapy. Eligible patients were adults with pathologically confirmed recurrent ESCC, and 82 patients were randomized 1:1 to Irinotecan (65 mg/m2/day 1 and day 8) with or without anlotinib (12 mg qd day 1 to 14) of a 21-day cycle till progression or intolerable. The primary endpoint is the disease control rate (DCR) and progression-free survival (PFS) and the secondary end points are objective response rate (ORR) and overall survival (OS). Results Between 13/1 2019 and 20/1 2020, a total of 43 patients were enrolled and randomly assigned to either the anlotinib plus irinotecan (n = 22) or the irinotecan group (n = 21).The mPFS was longer in trial group than in control group (89 days vs 66 days, HR = 0.447, P = 0.055). The Disease control rate (DCR) was 54.5% in trial group and 38.1% in the control group. The treatment-related adverse events (>10%) were fatigue (59.1%), nausea (50.0%), decreased appetite (36.4%), hoarseness (27.3%), thyroid-stimulating hormone elevation (22.7%), diarrhea (9.1%), and decreased lymphocytes count(9.1%) in trial group. Grade 3 AEs included fatigue (4.5% vs 4.8%), nausea (4.5% vs 0%) and diarrhea (4.5% vs 0%) in two groups. Conclusion Anlotinib plus irinotecan was similarly tolerable but prolonged PFS compared to irinotecan monotherapy as a second-line treatment in patients with recurrent ESCC.