Clinical efficacy and safety of apatinib in patients with advanced colorectal cancer as the late-line treatment

Abstract

There is currently no standard therapeutic regimen available for patients with advanced colorectal cancer in whom the disease continues to progress after 2 or more lines of chemotherapy. The purpose of this study is to investigate the efficacy and safety of apatinib in patients with advanced colorectal cancer for whom at least two lines of prior chemotherapy had failed.Twenty seven patients with advanced colorectal cancer who had failed at least 2 lines chemotherapy were treated with apatinib (500 mg/day). As a comparison control, 26 advanced colorectal cancer patients with comparable clinical baseline characteristics including age, sex, Eastern Cooperative Oncology Group (ECOG) score, pathological type, carcinoembryonic antigen (CEA) level, tumor location, number and location(s) of metastasis, and previous chemotherapies were subject to observation. Survival analyses were performed via the Kaplan–Meier method. The toxicity were evaluated in all patients this study according to the National Cancer Institute Common Toxicity Criteria 4 (NCI CTC version 4.0).A total of 53 well-matched patients with advanced colorectal cancer were retrospectively analyzed. The median follow-up time was 6.0 months (2.0–16.0 months). The median PFS was significantly longer for apatinib group than for observation group (2.0 vs. 1.1 months; HR = 3.88; 95% confidence interval [CI], 1.91–7.88; P < .001). However, there was no significant difference between the 2 groups for median OS (5.0 vs. 4.0 months; HR = 1.03; 95% CI, 0.56–1.90; P = .914). The disease control rate of the apatinib group was significantly better than that of the observation group (70.4% vs 26.9%, P = .002). There was no significant difference in the overall remission rate between the 2 groups (3.7% vs 0%, P = .322). Advanced colorectal cancer patients with 2 or fewer metastatic sites experienced longer PFS than those with more than 2 sites. High ECOG scores, cancer localization to the right side of colon and lymph node metastasis were associated with increased risk of death and all remained independent factors affecting OS. The most common grade 3/4 treatment-related adverse events were hypertension and hand-foot skin syndrome.Apatinib treatment for patients with advanced colorectal cancer who had failed chemotherapy achieved better disease control and prolonged PFS relative to untreated controls. The toxicity was manageable.

Apatinib Monotherapy for Chemotherapy-Refractory Metastatic Colorectal Cancer: A Multi-centre, Single-Arm, Prospective Study

“…The moderate initial dose in our study resulted in a more manageable toxicity profile and a lower proportion of dose modification than those in the previous studies of apatinib 850 mg in advanced gastric cancer 33,34 . Furthermore, it seems comparable to the modification reported in the studies of apatinib 500 mg in mCRC 10,[13][14][15][16] .…”

“…This finding further supports the use of apatinib as an alternative option based on the strategy of continued administration of newer anti-angiogenic agents as the new standard of care. In a retrospective case-controlled study, apatinib exhibited weaker survival outcomes with PFS and OS of 2.0 and OS 5.0 months, respectively, in late-line setting in mCRC 16 . We speculated that the inconsistency could be because the previous study had a relatively shorter follow-up time (6.0 months), higher proportion of patients with performants status of 2 (48.1%), smaller sample size (25 patients in apatinib group), and higher selection bias than those of our present study.…”

“…It is currently approved by China Food and Drug Administration (CFDA) for treatment in the third-line settings in the patients with metastatic gastric or gastroesophageal junction adenocarcinoma. Preclinical and clinical trials have shown its vigorous antitumour activity and good tolerability in multiple malignancies including non-small cell lung cancer, triple-negative breast cancer, ovarian cancer, and colorectal cancer 7,[9][10][11][12][13][14][15][16][17][18][19][20] , Presently, the evidence that apatinib may improve survival in chemotherapy-refractory mCRC is based on limited retrospective studies 10,13,15,16 . The impact of previous anti-angiogenic therapies on the efficacy of apatinib remains unknown.…”

Influence of KDR Genetic Variation on the Efficacy and Safety of Patients with Chemotherapy Refractory Metastatic CRC Who Received Apatinib Treatment

“…Management of the patients in retrospective study was not sufficient and normative compared with a well-designed phase ІІ clinical trial, which was demonstrated in the other retrospective study of apatinib in metastatic CRC (ORR=3.7%, DCR=70.4% and mPFS=2.0 months). 36 Additionally, it should be noted that the proportion of patients with ECOG 2 score in our study was higher than that in the phase ІІ study (43.5% vs 35.4%). To our knowledge, the previous research had suggested that higher ECOG score was associated with worse prognosis among patients with metastatic CRC.…”

Apatinib-loaded CalliSpheres Beads for embolization in a rabbit VX2 liver tumor: characterization in vitro , pharmacokinetics and tumor response in vivo

“…It has been approved as a second-line therapy in Chinese patients with advanced HCC. The systemic adverse events including gastrointestinal reaction, hypertension, abnormal coagulation function, proteinuria after oral administration were still common and even serious (Zhao et al., 2018 ), although improved survival occurred in advanced HCC, non-small-cell lung cancer and colorectal cancer (Liao et al., 2018 ; Wang et al., 2018 ; Wu et al., 2018 ). The local delivery of drug is a novel method to increase tumor drug concentration and reduce systemic toxicity (Zhou et al., 2020 ).…”