Ponatinib shows promise for advanced gastrointestinal stromal tumors

CHICAGO — Ponatinib demonstrated encouraging activity in patients with advanced gastrointestinal stromal tumors who had failed on previous therapy with a tyrosine kinase inhibitor, according to initial results of a phase 2 study presented at the ASCO Annual Meeting.

Michael C. Heinrich, MD, of Oregon Health and Science University’s Knight Cancer Institute, and colleagues conducted an initial analysis of 35 patients. The median age of the population was 58 years, and a median 6 years had elapsed since their diagnosis.

Seventy-four percent of patients had received four or more prior cancer therapies. Forty-six percent of patients had received two prior TKIs, and an additional 46% had received three prior TKIs.

Heinrich and colleagues divided patients into one of two cohorts based on KIT exon 11 mutation status. All patients received 45 mg daily ponatinib (Iclusig, Ariad).

Seventeen patients discontinued treatment — eight due to progressive disease, five due to adverse events and four due to other reasons.

Median follow-up for the KIT-positive cohort was 4 months, and follow-up for patients with wild-type KIT was 3 months.

In the KIT mutation cohort, researchers calculated a 55% clinical benefit rate — which included one partial response and 10 patients who achieved stable disease — after at least 16 weeks. The objective response rate for this cohort was 8% (n=2).

Five patients who had baseline PET scans demonstrated decreased fluorodeoxyglucose uptake in active lesions. All of these patients were still receiving study treatment with stable disease or better at the time of the analysis.

The clinical benefit rate of patients without a KIT mutation was 22% (n=2), and the objective response rate was 0%.

The most common treatment-emergent adverse events in both cohorts were rash (54%), fatigue (46%), myalgia (46%), dry skin (40%), headache (40%), abdominal pain (34%) and constipation (34%). Abdominal pain (11%), nausea (6%), vomiting (6%) and fatigue (6%) were the most common serious adverse events. One patient experienced myocardial ischemia, and one patient died due to pneumonia.

“Initial analysis of this ongoing trial suggests that ponatinib has activity in patients with advanced gastrointestinal stromal tumors after failure of prior TKI therapy,” the researchers concluded.

For more information:

Heinrich MC. Abstract #10506. Presented at: ASCO Annual Meeting; May 30-June 3, 2014; Chicago.

Disclosure: Researchers report consultant/advisory roles or employment/leadership positions with, stock ownership in, honoraria or research funding from, and expert testimony for Ariad Pharmaceuticals, Bayer, Blueprint Medicines, GlaxoSmithKline, MolecularMD, Novartis, Onyx and Pfizer.