Apatinib prolongs survival in advanced gastric cancer

Last Updated: 2016-02-19

By Will Boggs MD

NEW YORK (Reuters Health) - Treatment with the VEGFR-2 inhibitor apatinib prolongs survival in patients with chemotherapy-refractory advanced or metastatic gastric cancer, researchers from China report.

Apatinib improved overall survival and progression-free survival in an earlier phase II study of patients with chemotherapy-refractory advanced or metastatic gastric carcinoma, the team notes in the Journal of Clinical Oncology, online February 16.

Dr. Shukui Qin from 81st Hospital of People's Liberation Army in Nanjing and colleagues investigated the efficacy and safety of apatinib in a phase 3 placebo-controlled study of 267 patients with advanced or metastatic gastric or gastroesophageal junction adenocarcinoma for whom at least two lines of previous systemic chemotherapies had failed.

At the time of data cut-off, the mean overall survival was 6.5 months for the apatinib group versus 4.7 months for the placebo group (p=0.015), the team found.

Progression-free survival (PFS) averaged 2.6 months with apatinib and 1.8 months with placebo (p<0.001).

Objective response rates were 2.84% with apatinib and 0% with placebo, not a significant difference, and disease control rates were 42.05% for apatinib and 8.79% for placebo (p<0.001).

The groups did not differ in quality of life scores at any point, but grade 3 to 4 hand-foot skin reaction, hypertension, and proteinuria were more common among apatinib patients.

"These data demonstrate that apatinib could be a new treatment option for patients with metastatic gastric cancer experiencing progression after two or more lines of chemotherapy," the researchers conclude.

"On the basis of the data from this phase III study, apatinib was approved in October 2014 by the China Food and Drug Administration for metastatic gastric or gastroesophageal junction adenocarcinoma after second-line chemotherapy. A series of additional studies designed to assess the potential application of apatinib in other solid tumors such as non-small-cell lung cancer and hepatocellular carcinoma is ongoing," they note.

Dr. David H. Ilson, from Memorial Sloan-Kettering Cancer Center, New York, who wrote an editorial related to this report, told Reuters Health by email, "VEGF targeted therapy has modest activity in later-line treatment of advanced gastric cancer. These results are consistent with recent trials of the second-line use of ramucirumab."

"Current optimal use of these agents is the second-line use of paclitaxel plus ramucirumab in the U.S.," Dr. Ilson said. "These and other later-line agents will need to have cost analyses relative to the modest benefits; i.e., what is the cost per years of life increased?"

Dr. Richard D. Kim, from H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida, recently reviewed second-line treatments for advanced gastric cancer. He told Reuters Health by email, "This is another trial illustrating the benefit of VEGF inhibition in refractory gastric cancer, similar to ramucirumab. Similar to other TKIs (in other disease) there was an improvement in overall survival and PFS but no difference in response rate."

"The patients in this study were a very heavily treated patient population, which may not necessarily reflect the patients we see here in U.S.," Dr. Kim said. "Also since the trial was done in China a similar study should be repeated here in U.S. where ramucirumab is available in the second-line setting."

Jiangsu Hengrui Medicine and Shanghai Hengrui Pharmaceutical supported the trial. Jiangsu Hengrui Medicine employed one of the authors.

Dr. Qin did not respond to a request for comments.

SOURCE: bit.ly/1QpJUXl and bit.ly/1mLxvFq

J Clin Oncol 2016.