Anlotinib plus chemotherapy as first-line therapy for patients with gastrointestinal tumor with unresectable liver metastasis: Results from a multi-cohort, multicenter phase II trial (ALTER-G-001).
Authors: Zhou Chenfei , Wu Junwei , Yan Jun , Wang Chun , Mao Yong , Tang Xinyu , Zhu Lingjun , Chen Jun , Wang Chunbing , Qin Zhiquan , Han Zhengxiang , Shangguan Chengfang , Zhang Jun 
Published: June 2023

e16268 Background: Patients (pts) with advanced gastrointestinal (GI) tumors, such as colorectal cancer (CRC), esophageal squamous cell carcinoma (ESCC), gastric cancer (GC) or pancreatic cancer (PC), often developed liver metastases (LMs) with poor prognosis. Currently, there was no formal option for those, thus, more effective regimens were needed. Previously clinical trials had demonstrated anlotinib plus chemotherapy as first-line regimen had encouraging efficacy and safety in advanced CRC and ESCC, especially in pts with LMs. Therefore, we conducted a phase II trial evaluate efficacy and safety of anlotinib plus chemotherapy as first-line treatment in pts with unresectable LMs GI tumors. Methods: A total of 116 eligible pts with unresectable LMs gastrointestinal tumors and without previous systemic treatment would be divided into cohort A (mCRC), cohort B (ESCC) and cohort C (others, such as PC, GC, etc.,). All enrolled patients received 6 cycles (3 weeks per cycle) of induction therapy, cohort A receiving anlotinib (12mg, po, qd, d1-d14), oxaliplatin (130 mg/m2, iv, d1) and capecitabine (850 mg/m2, po, bid, d1-d14), cohort B receiving anlotinib, cisplatin (60-750 mg/m2, i.v., d1/d1-3) and paclitaxel (135 mg/m2, i.v., d1) or docetaxel (75 mg/m2, i.v., d1) and cohort C receiving anlotinib plus standard chemotherapy. Then, pts in all cohorts without PD and radical resection received anlotinib and metronomic capecitabine (500mg, po. bid, d1-21, q3w) until PD or unacceptable toxicity. The primary endpoint was ORR (RECIST 1.1). Secondary endpoints included DoR, PFS, OS, DCR, radical resection rate for LMs and safety. Results: As of February 8th, 2023, 55 pts were enrolled, 23 in cohort A, 2 in cohort B and 30 in cohort C (including 18 PC, 6 GC, 5 biliary tract cancer (BTC) and others), with a median age of 62.5 years old (range 34-74), 67.3% of male, 89.1% of ECOG PS 1. 70.9% of pts had LMs only. After induction therapy, 7 pts (5 CRC, 1 PC, 1 BTC) received surgical resection. In 24 evaluable pts in cohort C, 12 had partial response (PR), 9 had stable disease (SD). ORR was 50.0% and DCR was 87.5%. Among 13 evaluable pts with PC, 7 had PR, 5 had SD, with an ORR of 53.8%. In 15 evaluable pts in cohort A, 11 reached PR and 4 had SD. The ORR of cohort A was 73.3% and DCR was 100.0%. For one evaluable ESCC pts in cohort B, the best response was PR. The median PFS was not reached. 50.9% of pts had treatment emergent adverse events (TEAEs). Incidence of grade 3/4 TEAEs was 16.4%, mainly included white blood cell decreased (7.3%), neutropenia and hypertension (5.5%). Conclusions: Anlotinib plus chemotherapy showed significant efficacy and manageable toxicities as first-line treatment in advanced gastrointestinal tumors with LMs, especially in pancreatic cancer, which might provide a new treatment strategy for those. Clinical trial information: NCT05262335 .