Incyte has announced top-line results of the Phase II, randomized, double-blind, placebo-controlled RECAP trial of Ruxolitinib ( Jakafi ), its oral JAK1 and JAK2 inhibitor, in combination with Capecitabine ( Xeloda ) in patients with recurrent or treatment refractory metastatic pancreatic cancer.
The hazard ratio ( HR ) for overall survival in the intent to treat population was 0.79 ( one-sided p=0.12 ), and in a pre-specified subgroup analysis conducted in patients identified prospectively as most likely to benefit from JAK pathway inhibition, the HR for overall survival was 0.47 ( one-sided p=0.005 ).
Within this subgroup of patients, which represented 50% of the randomized population, 6 month survival in the Ruxolitinib arm was 42% vs. 11% for placebo.
Durable tumor responses were only observed in patients receiving Ruxolitinib, and Ruxolitinib treated patients achieved a significant improvement in body weight relative to placebo.

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.

The purpose of RECAP trial was to determine whether Ruxolitinib in combination with Capecitabine could improve the overall survival of patients with refractory metastatic pancreatic cancer as compared to Capecitabine alone.
RECAP included pre-specified analyses to determine the base line characteristics of patients most likely to benefit from treatment with Ruxolitinib.
The study included a total of 136 patients and consisted of an open-label, safety run-in period involving nine patients to determine the safety of the Ruxolitinib and Capecitabine combination. This was followed by a double-blind study of 127 patients randomized 1 to 1 to Capecitabine plus Ruxolitinib or Capecitabine plus placebo. Patients received treatment as long as the regimen was tolerated or the patient did not meet any of the discontinuation criteria.
In the event of disease progression, Capecitabine therapy was discontinued while treatment with Ruxolitinib or placebo continued unless patients withdrew consent for further participation in the trial.
In addition to the primary endpoint of overall survival, secondary endpoints included progression free survival, body weight and nutritional markers, tumor response rate, quality of life outcomes and pain status.

Ruxolitinib in combination with Capecitabine was generally well tolerated in this study. Among patients receiving Ruxolitinib plus Capecitabine 12% discontinued therapy for an adverse event, compared with 20% who received Capecitabine alone. The rates of new onset grade 3 anemia, thrombocytopenia or neutropenia were 16%, 2% and 0%, respectively, among patients receiving Ruxolitinib plus Capecitabine and were 2%, 3% and 2%, respectively, among patients receiving Capecitabine alone.

Pancreatic cancer is the fourth leading cause of cancer-related death in the US and the eighth leading cause of cancer-related death worldwide.
For patients with advanced pancreatic cancer, the 5-year overall survival rate is less than 1%. Most patients die within the first year. Pancreatic cancer has the lowest 5-year overall survival rate of any cancer in the US.
In Europe, the reported survival rate is less than 10% survival at five years.
Most patients do not exhibit symptoms until their disease is advanced. Additionally, pancreatic cancer progresses and metastasizes rapidly. ( Xagena )

Source: Incyte, 2013

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