Adding ruxolitinib to capecitabine significantly improved the survival rate of a subgroup of patients with recurrent or treatment-refractory pancreatic cancer compared with patients in the same population who received capecitabine alone.
Paul A. Friedman, MD
Ruxolitinib (Jakafi) significantly improved the survival rate of a subgroup of patients with recurrent or treatment-refractory pancreatic cancer—those who were expected to benefit from the drug the most when given in combination with the chemotherapy agent capecitabine—compared with patients in the same population who received capecitabine alone, according to top-line results of a phase II proof-of-concept study.
The drug’s manufacturer, Incyte, announced the results on Wednesday. Full results from the study are expected to be presented at a future scientific meeting.
Ruxolitinib is a potent and selective oral JAK1 and JAK2 inhibitor that was approved by the FDA in 2011 for the treatment of myelofibrosis, a form of blood cancer characterized by bone marrow failure and spleen enlargement.
In this phase II trial, known as the RECAP trial, patients with metastatic pancreatic cancer who had failed first-line treatment with gemcitabine, or another chemotherapy agent if they were ineligible to receive gemcitabine, received capectabine 2000 mg/m2 or 1000mg/m2 twice a day and were randomized to receive either ruxolitinib 15mg twice a day or a placebo.
The doses of capecitabine and ruxolitinib could be increased during the study, and patients received the drugs in continuous 21-day cycles as long as they were tolerated, with capecitabine being self-administered during the first 14 days of the cycle and ruxolitinib being self-administered during the entire cycle.
A subgroup analysis found that patients who were prospectively identified as more likely to benefit from JAK pathway inhibition—who represented 50% of the total patient population—had a survival rate at six months of 42% compared with 11% in similar patients who received a placebo (hazard ratio [HR] = 0.47; one-sided P = .005).
The announcement noted that durable tumor responses were only observed in patients who received ruxolitinib, and these patients also achieved a significant improvement in body weight relative to those on the placebo. In the study’s intent-to-treat population, the HR for improvement in overall survival was 0.79, though this was not considered statistically significant (one-sided P = .12).
Incyte also provided some safety data, with researchers finding that the combination of ruxolitinib and capecitabine was generally well tolerated in this study. The discontinuation rate as the result of an adverse event was 12% in the combination arm compared with 20% in the control arm.
The most frequently observed new-onset grade 3 adverse event in the combination arm was anemia, which occurred in 16% of patients compared with 2% of patients in the control arm. The rates of new onset-grade 3 thrombocytopenia and neutropenia were 2% and 0% in the combination arm, respectively, compared with 3% and 2% in the control arm, respectively.
“Results of the RECAP trial provide the first evidence that JAK inhibition is active in this disease and suggest a demonstrable survival benefit in a well-defined group of patients with refractory metastatic pancreatic cancer who can be identified without the development of a companion diagnostic test,” said Paul A. Friedman, MD, president and chief executive officer at Incyte, in a statement. “Coupled with the overall survival benefit observed in the ongoing Phase III trials in myelofibrosis, these results solidify our belief in the therapeutic opportunity that exists for Jakafi, and provide us with an acceleration strategy to advance our JAK1 inhibitor portfolio into additional areas of unmet medical need.”
Ruxolitinib is also under investigation for the treatment of chronic myeloid leukemia, breast cancer, non-Hodgkin lymphoma, and other indications in patients with myelofibrosis.