Among patients with metastatic pancreatic cancer, the addition of ruxolitinib to second-line capecitabine therapy was well tolerated but did not improve clinical outcomes, according to a study being presented at the 2017 Gastrointestinal Cancers Symposium.1
Because the JAK-STAT pathway plays a role in the pathogenesis of pancreatic cancer, researchers conducted a phase 2 study to evaluate the activity of JAK1/2 inhibition with ruxolitinib in combination with capecitabine among patients with metastatic pancreatic cancer and evidence of systemic inflammation. The study showed a survival benefit with the combination compared with capecitabine alone.
Researchers developed 2 phase 3 trials to assess the efficacy and safety of ruxolitinib plus capecitabine in patients with advanced pancreatic cancer requiring second-line therapy. For the Janus 1 trial (ClinicalTrials.gov Identifier: NCT02117479) and the Janus 2 trial (ClinicalTrials.gov Identifier: NCT02119663), investigators randomly assigned 321 and 86 patients, respectively, 1:1 to receive ruxolitinib plus capecitabine or placebo plus capecitabine.
Based on efficacy findings of a planned interim analysis, investigators terminated the study early. Results showed no significant difference in median overall survival between the 2 arms in either Janus 1 (hazard ratio [HR], 0.969; 95% CI, 0.75-1.26; P = .409) or Janus 2 (HR, 1.584; 95% CI, 0.89-2.83; P = .942).
In Janus 1, median progression-free survival was 43 days with ruxolitinib vs 44 days with placebo (HR, 1.056; 95% CI, 0.83-1.35; P = .666); median progression-free survival was 48 days and 61 days, respectively, in the Janus 2 study (HR, 1.166; 95% CI, 0.69-1.98; P = .720).
Less than 5% of patients in each treatment group achieved an overall response.
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The most common grade 3 to 4 non-hematologic adverse events were abdominal pain, palmar-plantar erythrodysesthesia syndrome, pulmonary embolism, dyspnea, and vomiting. The most frequent grade 3 to 4 hematologic abnormalities were anemia and lymphopenia. Four percent of ruxolitinib-treated patients in Janus 1 and 12% in Janus 2 discontinued treatment due to adverse events compared with 10% and 12% of patients given placebo in Janus 1 and Janus 2, respectively.
- Hurwitz H, Van Cutsem E, Bendell JC, et al. Two randomized, placebo-controlled phase 3 studies of ruxolitinib (Rux) + capecitabine (C) in patients (pts) with advanced/metastatic pancreatic cancer (mPC) after failure/intolerance of first-line chemotherapy: JANUS 1 (J1) and JANUS 2 (J2). J Clin Oncol. 2017;35(suppl):4S. Abstract 343.