Drug combo may extend survival in advanced pancreas cancer

Last Updated: 2015-04-20

By Larry Hand

NEW YORK (Reuters Health) - Two subsets of patients with inoperable pancreatic ductal adenocarcinoma (PDAC) had extended survival with gemcitabine plus masitinib in an international phase 3 trial.

Dr. Gael Deplanque of Saint Joseph Hospital, Paris, France and colleagues randomly assigned 353 patients from 73 centers to receive oral masitinib 9 mg/kg/day plus gemcitabine 1000 mg/m2 daily, or gemcitabine plus placebo.

For the study population as a whole, the combination didn't prolong overall survival. Median overall survival was 7.7 months for the combination treatment and 7.1 months for gemcitabine plus placebo, the researchers reported online April 9 in Annals of Oncology.

But patients with overexpression of the ACOX1 gene and patients with higher baseline pain intensities based on visual analog scale (VAS) fared better.

Among those with ACOX1 overexpression, median overall survival was 5.6 months in the 20 individuals who received gemcitabine plus placebo, vs 11.7 months in the 20 patients who also received masitinib (p=0.001).

And patients with higher baseline pain intensities also had better overall survival with masitinib (8.0 vs 5.4 months; p=0.012).

Toxicity was increased with the combination treatment, but side effects were manageable, the researchers reported.

The researchers say the two subgroups combined may represent 63% of the PDAC population.

"The survival benefit observed for PDAC patients with overexpression of ACOX1 in blood or reporting baseline pain of VAS >20 mm when treated with masitinib plus gemcitabine, coupled with manageable toxicity, suggests a positive benefit-risk ratio," the researchers concluded.

Masitinib (AB Science; Paris, France) is a tyrosine kinase inhibitor that has regulatory approval for treating mast cell tumors in animals and is under investigation for multiple human indications. The authors speculate that patients with high baseline pain and overexpression of ACOX1 may have increased mast cell activity in the tumor microenvironment.

A confirmatory study is under way that may validate use of masitinib plus gemcitabine "as a new treatment option for these two subgroups of PDAC patients," the researchers wrote.

The researchers did not respond to requests for comment. AB Science representatives declined to comment.

AB Science and Acobiom, both in France, funded this research and employed five of the 16 authors; another three coauthors reported consulting for AB Science.

SOURCE: http://bit.ly/1ES2GVZ

Ann Oncol 2015.