Joyce O'Shaughnessy1, Angela DeMichele2, Cynthia X Ma3, Paul Richards4, Denise A Yardley5, Gail Shaw Wright6, Kevin Kalinsky7, Ronald Steis8, Sami Diab9, Gerard Kennealey10, Ryan Geschwindt10, Wei Jiang10, Hope S Rugo11. 1. Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, TX, USA. joyce.oshaughnessy@usoncology.com. 2. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 3. Washington University School of Medicine, St Louis, MO, USA. 4. Oncology & Hematology Associates of Southwest Virginia, Inc, Salem, VA, USA. 5. Sarah Cannon Research Institute and Tennessee Oncology PLLC, Nashville, TN, USA. 6. Florida Cancer Specialists, St. Petersburg, FL, USA. 7. Columbia University Medical Center, New York, NY, USA. 8. Northside Hospital, Inc, Atlanta, GA, USA. 9. Rocky Mountain Cancer Centers, Aurora, CO, USA. 10. Incyte Corporation, Wilmington, DE, USA. 11. University of California San Francisco Comprehensive Cancer Center, San Francisco, CA, USA.
Abstract
PURPOSE: The Janus-associated kinase (JAK)/signal transducer and activator of transcription pathway is a key regulator of inflammatory signaling, associated with tumorigenesis, cell survival, and progression. This randomized phase 2 trial evaluated the efficacy and safety of the addition of ruxolitinib, a JAK1/JAK2 inhibitor, to capecitabine in patients with HER2-negative advanced breast cancer and high systemic inflammation (modified Glasgow Prognostic Score [mGPS] ≥ 1). METHODS:Patients with ≤ 2 prior chemotherapy regimens for advanced or metastatic disease or hormone receptor-positive patients with disease progression on prior hormonal therapies were randomized 1:1 to 21-day cycles of ruxolitinib (n = 76) or placebo (n = 73) plus capecitabine. The primary endpoint was overall survival (OS). RESULTS: Baseline characteristics were well balanced between groups. For ruxolitinib plus capecitabine versus placebo plus capecitabine, median OS was 11.2 months versus 10.9 months (log-rank test P = 0.762); median progression-free survival (PFS) was 4.5 months versus 2.5 months (log-rank test P = 0.151); and overall response rate (ORR) was 28.9% versus 13.7% (Cochran-Mantel-Haenszel test P = 0.024), respectively. A more favorable change in health-related quality of life (HRQoL) was observed with ruxolitinib plus capecitabine versus placebo plus capecitabine. Both regimens were generally tolerable. A higher incidence of grade 3/4 anemia (25.4% vs 5.6%) and a lower incidence of grade 3/4 palmar-plantar erythrodysesthesia (1.4% vs 12.7%) occurred with ruxolitinib plus capecitabine versus placebo plus capecitabine. CONCLUSIONS: The addition of ruxolitinib to capecitabine for patients with advanced breast cancer and high systemic inflammation was generally tolerable; ORR was numerically greater, a more favorable change in HRQoL was observed, but neither OS nor PFS was improved compared with placebo plus capecitabine.
RCT Entities:
PURPOSE: The Janus-associated kinase (JAK)/signal transducer and activator of transcription pathway is a key regulator of inflammatory signaling, associated with tumorigenesis, cell survival, and progression. This randomized phase 2 trial evaluated the efficacy and safety of the addition of ruxolitinib, a JAK1/JAK2 inhibitor, to capecitabine in patients with HER2-negative advanced breast cancer and high systemic inflammation (modified Glasgow Prognostic Score [mGPS] ≥ 1). METHODS:Patients with ≤ 2 prior chemotherapy regimens for advanced or metastatic disease or hormone receptor-positive patients with disease progression on prior hormonal therapies were randomized 1:1 to 21-day cycles of ruxolitinib (n = 76) or placebo (n = 73) plus capecitabine. The primary endpoint was overall survival (OS). RESULTS: Baseline characteristics were well balanced between groups. For ruxolitinib plus capecitabine versus placebo plus capecitabine, median OS was 11.2 months versus 10.9 months (log-rank test P = 0.762); median progression-free survival (PFS) was 4.5 months versus 2.5 months (log-rank test P = 0.151); and overall response rate (ORR) was 28.9% versus 13.7% (Cochran-Mantel-Haenszel test P = 0.024), respectively. A more favorable change in health-related quality of life (HRQoL) was observed with ruxolitinib plus capecitabine versus placebo plus capecitabine. Both regimens were generally tolerable. A higher incidence of grade 3/4 anemia (25.4% vs 5.6%) and a lower incidence of grade 3/4 palmar-plantar erythrodysesthesia (1.4% vs 12.7%) occurred with ruxolitinib plus capecitabine versus placebo plus capecitabine. CONCLUSIONS: The addition of ruxolitinib to capecitabine for patients with advanced breast cancer and high systemic inflammation was generally tolerable; ORR was numerically greater, a more favorable change in HRQoL was observed, but neither OS nor PFS was improved compared with placebo plus capecitabine.
Authors: Nicholas P McAndrew; Lisa Bottalico; Clementina Mesaros; Ian A Blair; Patricia Y Tsao; Jennifer M Rosado; Tapan Ganguly; Sarah J Song; Phyllis A Gimotty; Jun J Mao; Angela DeMichele Journal: NPJ Breast Cancer Date: 2021-01-22
Authors: Humaid O Al-Shamsi; Ibrahim Abu-Gheida; Ahmed S Abdulsamad; Aydah AlAwadhi; Sadir Alrawi; Khaled M Musallam; Banu Arun; Nuhad K Ibrahim Journal: Oncologist Date: 2021-08-14
Authors: Su Yon Jung; Jeanette C Papp; Eric M Sobel; Matteo Pellegrini; Herbert Yu; Zuo-Feng Zhang Journal: Front Oncol Date: 2021-02-03 Impact factor: 6.244