Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy: JANUS 1 and 2 randomized phase III studies.

Autor:	Hurwitz, Herbert, Van Cutsem, Eric, Bendell, Johanna, Hidalgo, Manuel, Li, Chung-Pin, Salvo, Marcelo Garrido, Macarulla, Teresa, Sahai, Vaibhav, Sama, Ashwin, Greeno, Edward, Yu, Kenneth H., Verslype, Chris, Dawkins, Fitzroy, Walker, Chris, Clark, Jason, O’Reilly, Eileen M.
Předmět:	THERAPEUTIC use of antimetabolites ANEMIA ANTIMETABOLITES C-reactive protein CANCER chemotherapy COMBINATION drug therapy CONFIDENCE intervals DRUG tolerance HEMATOLOGIC agents METASTASIS PANCREATIC tumors SURVIVAL TUMOR classification FUTILE medical care RANDOMIZED controlled trials TREATMENT effectiveness DISEASE progression ODDS ratio PROGNOSIS
Zdroj:	Investigational New Drugs; Aug2018, Vol. 36 Issue 4, p683-695, 13p
Abstrakt:	Background Ruxolitinib, a Janus kinase 1 (JAK1)/JAK2 inhibitor, plus capecitabine improved overall survival (OS) vs capecitabine in a subgroup analysis of patients with metastatic pancreatic cancer and systemic inflammation (C-reactive protein [CRP] >13 mg/dL) in the randomized phase II RECAP study. We report results from two randomized phase III studies, JANUS 1 (NCT02117479) and JANUS 2 (NCT02119663). Patients and Methods Adults with advanced/metastatic pancreatic cancer, one prior chemotherapy regimen and CRP >10 mg/L were randomized 1:1 (stratified by modified Glasgow Prognostic Score [1 vs 2] and Eastern Cooperative Oncology Group performance status [0/1 vs 2]) to 21-day cycles of ruxolitinib 15 mg twice daily plus capecitabine 2000 mg/m2/day (Days 1-14) or placebo plus capecitabine. The primary endpoint was OS. Results Both studies were terminated following a planned interim futility/efficacy analysis of JANUS 1. Overall, 321 and 86 patients were randomized in JANUS 1 (ruxolitinib: n = 161; placebo: n = 160) and JANUS 2 (ruxolitinib: n = 43; placebo: n = 43). There was no significant difference in OS or progression-free survival (PFS) between treatments in JANUS 1 (OS: hazard ratio [HR], 0.969, 95% confidence interval [CI], 0.747-1.256; PFS: HR, 1.056; 95% CI, 0.827-1.348) or JANUS 2 (OS: HR, 1.584; 95% CI, 0.886-2.830; PFS: HR, 1.166; 95% CI, 0.687-1.978). The most common hematologic adverse event was anemia. No new safety signals with ruxolitinib or capecitabine were identified. Conclusions Ruxolitinib plus capecitabine was well tolerated in refractory pancreatic cancer patients; this combination did not improve survival. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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