Low-Dose Apatinib Combined With S-1 in Refractory Metastatic Colorectal Cancer: A Phase 2, Multicenter, Single-Arm, Prospective Study

Ning Li, Wenying Deng, Guifang Zhang, Yali Du, Yanwei Guo, Yijie Ma, Chen Wei, Liangyu Bie, Chi Zhang, Tao Song, Suxia Luo, Baijun Fang, Ning Li, Wenying Deng, Guifang Zhang, Yali Du, Yanwei Guo, Yijie Ma, Chen Wei, Liangyu Bie, Chi Zhang, Tao Song, Suxia Luo, Baijun Fang

Abstract

Purpose: Apatinib is an approved third-line treatment for metastatic gastric cancer in China and demonstrates good safety, tolerability, and efficacy in other advanced solid tumors. The aim of this prospective, single-arm, multicenter, phase 2 study was to assess the efficacy and safety of low-dose apatinib combined with S-1 in the treatment of refractory mCRC.

Patients and methods: Patients with refractory mCRC were enrolled and administered apatinib combined with S-1 until disease progression, patient decision to withdraw, or unacceptable toxic effects. The primary endpoint was investigator-evaluated progression-free survival (PFS) and the secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR).

Results: From December 2017 to December 2018, 30 patients were enrolled and 29 patients were eligible for the evaluation of efficacy and safety. The median PFS (mPFS) and OS (mOS) were 7.9 and 12.9 months, respectively. Exploratory analysis revealed that patients administered S-1 ≥ 70 days achieved longer mPFS and mOS. Four patients achieved a partial response, 22 achieved stable disease, and three had progressive disease, attributing to an ORR of 13.79% and a DCR of 89.66%. Ten grade 3 adverse events were reported and the frequency of each grade 3 adverse event was less than 5%. No grade 4 side events were observed.

Conclusions: These results indicated that apatinib combined with S-1 showed promising efficacy and manageable toxicity in patients with progressive mCRC after at least 2 prior lines of therapy, making it a promising therapeutic option for mCRC treatment.

Clinical trial registration: https://ichgcp.net/clinical-trials-registry/NCT03397199, identifier NCT03397199.

Keywords: S-1; apatinib; colorectal cancer; efficacy; metastatic.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Li, Deng, Zhang, Du, Guo, Ma, Wei, Bie, Zhang, Song, Luo and Fang.

Figures

Figure 1
Figure 1
Waterfall plot of best reduction in tumor size compared with baseline. Bar graph depicting the best percentage change in tumor size compared to baseline in 29 patients. * patient evaluation of tumor is SD, but pleural effusion increased significantly.
Figure 2
Figure 2
Summary of 29 patients treated with low-dose apatinib and S1. (A) progression-free survival (PFS). (B) overall survival (OS).
Figure 3
Figure 3
Kaplan-Meier curves for progression-free survival (PFS) and overall survival (OS). (A) Progression free survival in 29 patients. (B) Overall survival in 29 patients.

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