Efficacy and safety of intermittent versus continuous dose apatinib plus docetaxel as second-line therapy in patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma: a randomized controlled study

Abstract

Background: Previous studies of the second-line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma (GC/GEJAC) had reported that apatinib combined with chemotherapy improved the treatment outcomes. However, the benefits were sometimes limited due to the tolerance of continuous dose regimen. This randomized controlled study aimed to investigate the efficacy and safety of intermittent or continuous dose apatinib plus docetaxel as a second-line therapy in patients with advanced GC/GEJAC. Methods: Advanced GC/GEJAC patients who failed first-line chemotherapy were recruited (enrollment time: from September 15, 2017 to July 21, 2019), and randomly assigned to either the intermittent dose group (IG group) or the continuous dose group (CG group) (1:1 ratio) using the block randomization method. In the IG group, patients received apatinib 500 mg/d for 5 consecutive days then held for 2 days plus docetaxel 60 mg/m 2 q3w, in a 3-week cycle. In the CG group, patients received apatinib 500 mg daily plus docetaxel 60 mg/m 2 q3w, in a 3-week cycle. The progression free survival (PFS) was evaluated every two cycles and follow-ups were performed monthly. The primary endpoint was PFS, and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.Results: In total, 76 eligible patients were enrolled and randomly assigned (1:1 ratio). The IG group exhibited similar PFS compared to the CG group [median PFS: 3.88 (95% CI: 1.72-6.03) months vs. 3.98 (95% CI: 1.06-6.90) months, P=0.546] and OS [median OS: 9.00 (95% CI: 5.31-12.70) months vs. 9.40 (95% CI: 5.20-13.59) months, P=0.310]. ORR (21.1% vs. 18.4%, P=0.773) and DCR (60.5% vs. 60.5%, P=1.000) were of not statistically different between the IG and CG groups. As for safety, the IG group exhibited less frequent hypoproteinemia (31.6% vs. 55.3%, P=0.037) and lactate dehydrogenase increased (18.4% vs. 44.7%, P=0.014), while no differences in other adverse events were observed between the two groups.Conclusions: Intermittent dose apatinib plus docetaxel was equally effective and more tolerable than continuous dose apatinib plus docetaxel as a second-line therapy in patients with advanced GC/GEJAC.

Evaluation of second-line apatinib plus irinotecan as a treatment for advanced gastric adenocarcinoma or gastroesophageal conjunction adenocarcinoma: a prospective, multicenter phase II trial

“…The current study was a prospective, multicenter, phase II clinical study focusing on second-line apatinib plus irinotecan in patients with advanced GAC or GEJA, which could further verify the therapeutic potential of second-line apatinib plus irinotecan for the treatment of these patients. The data revealed that the ORR and DCR were 28.6% and 75.0%, respectively, in advanced GAC or GEJA patients who received second-line apatinib plus irinotecan, which was within the range of previous study-reported ORR and DCR (15)(16)(17)(18)(19)(20)(21). In addition, the ORR and DCR were numerically higher than those in advanced GAC patients receiving second-line chemotherapy (19).…”

“…Meanwhile, apatinib, an oral tyrosine kinase inhibitor that also targets VEGF receptor-2, has been recommended as the third-line treatment for advanced GAC and GEJA in China since it dramatically prolongs progression-free survival in patients with advanced GAC and GEJA (9,14). In the last two years, some clinical studies have shown that advanced GAC or GEJA patients who receive second-line apatinib plus chemotherapy present satisfactory response and survival, suggesting that apatinib plus chemotherapy may serve as a potential second-line therapy for advanced GAC and GEJA (14)(15)(16)(17)(18)(19)(20)(21). In addition, a recent phase II study investigating ramucirumab plus irinotecan as second-line therapy in patients with advanced GAC also reveals the efficacy and safety of VEGF receptor-2 inhibitor plus irinotecan in those patients (22).…”

Meta-Analysis of Efficacy and Safety of Karelizumab Combined with Apatinib in the Treatment of Advanced Gastric Cancer

“…After the duplicate literatures were eliminated, the titles and abstracts of the literatures were read. Based on the inclusion criteria and exclusion criteria, 20 literatures were finally included in this systematic analysis [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. The screening process is shown in Figure 1.…”

“…All the included 20 literatures [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] reported DCR, and the heterogeneity among 20 studies was low (P = 0:87, I 2 = 0%). The fixed effect model was used to analyze the data, which showed that the ROO of gastric cancer patients in the observation group was significantly higher than that in the blank group (OR = 3:09, 95% CI [2.29, 4.16], P < 0:01), as recorded in Figure 4 for details.…”

“…Literature Quality. Review Manager 5.3 software was used to evaluate the literature quality of 20 included[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] literatures by Cochrane risk bias evaluation tool. The overall quality of the 20 included in this study was low.…”