Ruxolitinib-Capecitabine May Benefit Patients With Gemcitabine-Pretreated Metastatic Pancreatic Cancer With Systemic Inflammation
In a randomized phase II trial reported in the Journal of Clinical Oncology, Hurwitz et al found no significant survival benefit of adding the JAK1/JAK2 inhibitor ruxolitinib (Jakafi) to capecitabine in patients with advanced pancreatic adenocarcinoma who had treatment failure with gemcitabine. However, a preplanned analysis indicated benefit among patients with evidence of higher systemic inflammation. The JAK/STAT pathway appears to play a role in pancreatic cancer and is a mediator of inflammatory responses in both tumor and normal tissue.
Study Details
In the double-blind trial, 127 patients from 41 U.S. sites were randomly assigned to receive ruxolitinib 15 mg twice daily plus capecitabine 1,000 mg/m2 twice daily (n = 64) or placebo plus capecitabine (n = 63). The primary endpoint was overall survival. A prespecified subgroup analysis assessed outcome in patients with serum C-reactive protein (CRP) levels above and below the median for the study population.
For the ruxolitinib and placebo groups, median age was 66 and 68 years, Karnofsky performance status was 80 to 100 in 75% and 90%, and metastasis sites were liver in 69% and 65% and lung in 45% and 44%; 25% and 14% had prior radiotherapy, 30% and 18% had prior surgery, 58% and 73% had normal/high albumin, and 27% and 33% had high lactate dehydrogenase. Modified Glasgow Prognostic Score (a systemic inflammation-based system) was 0 in 36% and 44%, 1 in 22% and 32%, 2 in 34% and 22%, and missing in 8% and 2%; a score of 0 indicates CRP level of ≤10 mg/L and a score of 1 or 2 indicates CRP of > 10 mg/L.
Survival Outcomes
Median follow-up was 4.4 months. Median overall survival was 4.5 months in the ruxolitinib group vs 4.3 months in the placebo group (hazard ratio [HR] = 0.79, P = .25); the HR for progression-free survival was 0.75 (P = .14). Probability of survival at 3, 6, and 12 months was 64%, 42%, and 22% vs 58%, 35%, and 11%.
In the prespecified subgroup analysis of patients with inflammation defined by serum CRP levels greater than the study population median (> 13 mg/L; 31 in ruxolitinib group, 29 in placebo group), median overall survival was 2.7 vs 1.8 months (HR = 0.47, P = .011), with survival at 3, 6, and 12 months of 48%, 42%, and 11% vs 29%, 11%, and 0%. The HR among patients with CRP levels ≤ 13 mg/L was 0.89 (P =.70). In a post hoc analysis, survival appeared to be better with ruxolitinib among patients with a Modified Glasgow Prognostic Score of 1 or 2 (HR = 0.60, P = .063) than among those with a score of 0 (HR = 0.91, P =.77).
Adverse Events
Adverse events of ≥ grade 3 occurred in 75% and 82% of patients. Those that were more common in the ruxolitinib group included anemia (15% vs 2%), pulmonary embolism (12% vs 5%), pneumonia (8% vs 2%), and stomatitis (7% vs 0%).
The investigators concluded: “Ruxolitinib plus capecitabine was generally well tolerated and may improve survival in patients with metastatic pancreatic cancer and evidence of systemic inflammation.”
Herbert I. Hurwitz, MD, of Duke University Medical Center, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by Incyte Corporation. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
