Therapeutic effect of apatinib on overall survival is mediated by prolonged progression-free survival in advanced gastric cancer patients

Abstract

Apatinib is reported to significantly improve the overall survival (OS) of patients with advanced gastric cancer who have previously failed second-line chemotherapy. However, it is not well understood whether apatinib acts by improving progression or by prolonging post-progression survival. Here, based on phase III clinical trial data, the mediating effect of apatinib on patient overall survival was systematically quantified, through progression-free survival (PFS), post-progression survival (PPS), and the disease control rate (DCR). PFS was the primary mediator of the association between apatinib treatment and OS, with an indirect-effect mean survival time ratio of 1.63 (95%CI 1.35-1.97), which mediated 93.5% of the treatment effect. The DCR was also a significant mediator among secondary efficacy endpoints, and had an indirect-effect mean survival time ratio of 1.47 (95%CI 1.20-1.79, 50.9% mediated). Both primary and other targets of the DCR had similar results. The results indicated that apatinib treatment prolongs progression-free survival rather than post-progression survival, and in turn, leads to improved overall survival. Additionally, our study highlights the value of mediation analysis in clinical trials in providing additional information to build upon traditional primary analysis.

Fatal hemoptysis in patients with advanced esophageal cancer treated with apatinib

“…Apatinib is a novel, oral, small molecule, anti-angiogenic agent, which has shown good survival benefits for gastric cancer and esophagogastric junction adenocarcinoma in Phase III clinical trials 4–7. However, the efficacy of treating esophageal cancer with apatinib is not clear.…”

Advanced alveolar soft part sarcoma responds to apatinib

“…The drug was approved by the China Food and Drug Administration in December 2014 for treatment of metastatic gastric cancer patients. Apatinib can improve progression-free survival, and consequently overall survival, in advanced gastric cancer patients [ 13 ]. Apatinib could potentially augment therapeutic options in a variety of sarcomas, including angiosarcoma, malignant fibrous histiocytoma, and myxoid/round cell liposarcoma [ 14 – 16 ].…”

Gastric cancer: Basic aspects

“…Apatinib (Rivoceranib ® ) is a novel potent small inhibitor acting through the selective binding to the tyrosine kinase domain of VEGFR2, and the consequent impairment of endothelial cell proliferation and migration. Having been clinically approved in China, apatinib‐based monotherapy showed no signs of excessive or unpredicted toxicity and was able to effectively prolong the median OS and PFS of GC patients with advanced disease in both phase II and phase III clinical trials . Of extreme relevance is the apparent efficacy of apatinib in highly resistance refractory tumors.…”

“…Having been clinically approved in China, apatinib-based monotherapy showed no signs of excessive or unpredicted toxicity and was able to effectively prolong the median OS and PFS of GC patients with advanced disease in both phase II and phase III clinical trials. [37][38][39] Of extreme relevance is the apparent efficacy of apatinib in highly resistance refractory tumors.…”