Famitinib versus placebo in the treatment of refractory metastatic colorectal cancer: a multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial

Rui-Hua Xu, Lin Shen, Ke-Ming Wang, Gang Wu, Chun-Mei Shi, Ke-Feng Ding, Li-Zhu Lin, Jin-Wan Wang, Jian-Ping Xiong, Chang-Ping Wu, Jin Li, Yun-Peng Liu, Dong Wang, Yi Ba, Jue-Ping Feng, Yu-Xian Bai, Jing-Wang Bi, Li-Wen Ma, Jian Lei, Qing Yang, Hao Yu, Rui-Hua Xu, Lin Shen, Ke-Ming Wang, Gang Wu, Chun-Mei Shi, Ke-Feng Ding, Li-Zhu Lin, Jin-Wan Wang, Jian-Ping Xiong, Chang-Ping Wu, Jin Li, Yun-Peng Liu, Dong Wang, Yi Ba, Jue-Ping Feng, Yu-Xian Bai, Jing-Wang Bi, Li-Wen Ma, Jian Lei, Qing Yang, Hao Yu

Abstract

Background: Metastatic colorectal cancer (mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC.

Methods: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), quality-of-life (QoL), and safety.

Results: Between July 18, 2012 and Jan 22, 2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib (n = 99) or placebo (n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups (hazard ratio = 0.60, 95% confidence interval = 0.41-0.86, P = 0.004). The DCR was 59.8% and 31.4% (P = 0.002) and the ORR was 2.2% and 0.0% (P = 0.540) in the famitinib and placebo groups, respectively. The most frequent grade 3-4 adverse events were hypertension (11.1%), hand-foot syndrome (10.1%), thrombocytopenia (10.1%), and neutropenia (9.1%). Serious adverse events occurred in 11 (11.1%) patients in the famitinib group and 5 (9.1%) in the placebo group (P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months (P = 0.657).

Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability. Trial registration This study was registered on ClinicalTrials.gov (NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal Symposium.

Keywords: Colorectal cancer; Efficacy; Famitinib; Safety.

Figures

Fig. 1
Fig. 1
The flow diagram of patient enrollment for the phase II clinical trial of famitinib versus placebo in the treatment of refractory metastatic colorectal cancer (mCRC)
Fig. 2
Fig. 2
Kaplan–Meier estimates of progression-free survival (PFS) and overall survival (OS) probability of mCRC patients treated with famitinib and placebo. a the median PFS in the famitinib group was significantly longer than that in the placebo group (P = 0.004); b there is no significant difference in the median OS between the two groups
Fig. 3
Fig. 3
Factors associated with PFS of mCRC patients as identified by stratified analysis. LDH lactate dehydrogenase, ULN upper limit of normal, HR hazard ratio, 95% CI 95% confidence interval
Fig. 4
Fig. 4
Mean overall quality of life (QoL) score of mCRC patients over early study visits at baseline and during famitinib or placebo treatment. All data points are presented as mean ± standard deviation

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