Efficacy and safety of anlotinib plus XELOX regimen as first-line therapy for mCRC: a single-arm, multicenter, phase II study (ALTER-C-001)

Bo Song; Hai Hu; Li Zhang; Su-Juan Ye; Yong-Dong Jin; Chang-Ling Shang; Jun Zhang; Hao Sun; Ke Zhang; Bo Yi; Yun-Wei Han; Jin Yan

doi:10.3389/fonc.2023.1238553

Efficacy and safety of anlotinib plus XELOX regimen as first-line therapy for mCRC: a single-arm, multicenter, phase II study (ALTER-C-001)

Front Oncol. 2023 Sep 1:13:1238553. doi: 10.3389/fonc.2023.1238553. eCollection 2023.

Authors

Bo Song¹, Hai Hu¹, Li Zhang², Su-Juan Ye³, Yong-Dong Jin⁴, Chang-Ling Shang³, Jun Zhang², Hao Sun⁵, Ke Zhang¹, Bo Yi¹, Yun-Wei Han³, Jin Yan¹

Affiliations

¹ Department of Gastrointestinal Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
² Department of Medical Oncology, Chongqing University Three Gorges Hospital, Chongqing, China.
³ Department of Medical Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
⁴ Department of Medical Oncology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
⁵ Gastrointestinal Cancer Center, Chongqing University Cancer Hospital, Chongqing, China.

Abstract

Background: Anlotinib showed encouraging anti-tumor activity in metastatic colorectal cancer (mCRC). This study was designed to assess the efficacy and safety of anlotinib plus XELOX as first-line therapy in mCRC patients.

Materials and methods: Eligible patients aged ≥18 with mCRC were enrolled in this multicenter, single-arm, phase II, exploratory study. Patients received at least 6 cycles of anlotinib, oxaliplatin, and capecitabine as initial therapy. Subsequently, patients received anlotinib monotherapy as maintenance therapy until tumor progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS).

Results: Thirty-one patients were included between December 2019 and March 2022. The median follow-up was 17.5 (95% CI, 3.0-17.5) months. The median PFS was 8.3 (95% CI, 6.3-10.0) months, with 6- and 12-month PFS rates of 82.3% (95% CI, 59.2%-93.0%) and 18.9% (95% CI, 4.8%-40.1%), respectively. Fifteen (48.4%) achieved partial response for an ORR of 48.4% (95% CI, 30.2%-66.9%). The disease control rate was 71.0% (95% CI, 52.0%-85.8%) due to 7 (22.6%) stable diseases. The median duration of response was 6.0 (95% CI, 3.6-8.0) months and 1 patient had the longest ongoing response of 17.3 months. Of 24 patients with evaluable imaging, 23 (74.2%) obtained tumor shrinkage. The median PFS (11.0 vs. 6.9 months) and ORR (66.7% vs. 60.0%) for patients with RAS/BRAF wild-type were numerically better than those with mutation. Three patients are still ongoing treatment. The grade 3 or more treatment-emergent adverse events (TEAEs) were mainly hypertension (12.9%) and decreased neutrophil count (12.9%). Four (12.9%) had serious TEAEs, primarily including abdominal pain and incomplete intestinal obstruction.

Conclusion: Anlotinib plus XELOX as first-line therapy in patients with mCRC showed anti-tumor activity and safety profile, which is worth further investigation.

Clinical trial registration: chictr.org.cn, identifier ChiCTR1900028417.

Keywords: XELOX; anlotinib; efficacy; first-line therapy; metastatic colorectal cancer; safety.