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A randomized, double-blind, phase 2 study of ruxolitinib or placebo in combination with capecitabine in patients with advanced HER2-negative breast cancer and elevated C-reactive protein, a marker of systemic inflammation

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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.

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Acknowledgements

We thank the patients, their families, and their caregivers for participating in the trial. Medical writing assistance was provided by Abigail Marmont, Evidence Scientific Solutions Inc., Wilmslow, UK, and funded by Incyte Corporation.

Author information

Authors and Affiliations

  1. Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, TX, USA

    Joyce O’Shaughnessy

  2. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Angela DeMichele

  3. Washington University School of Medicine, St Louis, MO, USA

    Cynthia X. Ma

  4. Oncology & Hematology Associates of Southwest Virginia, Inc, Salem, VA, USA

    Paul Richards

  5. Sarah Cannon Research Institute and Tennessee Oncology PLLC, Nashville, TN, USA

    Denise A. Yardley

  6. Florida Cancer Specialists, St. Petersburg, FL, USA

    Gail Shaw Wright

  7. Columbia University Medical Center, New York, NY, USA

    Kevin Kalinsky

  8. Northside Hospital, Inc, Atlanta, GA, USA

    Ronald Steis

  9. Rocky Mountain Cancer Centers, Aurora, CO, USA

    Sami Diab

  10. Incyte Corporation, Wilmington, DE, USA

    Gerard Kennealey, Ryan Geschwindt & Wei Jiang

  11. University of California San Francisco Comprehensive Cancer Center, San Francisco, CA, USA

    Hope S. Rugo

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  1. Joyce O’Shaughnessy
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Corresponding author

Correspondence to Joyce O’Shaughnessy.

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Conflict of interest

RG and WJ are employees of Incyte Corporation. GK is a contractor for Incyte Corporation. AD has received research funding from Incyte (institutional). HSR received research funding from Incyte for this trial. JOS, CXM, PR, DAY, GSW, KK, RS, and SD have no financial relationship with Incyte.

Ethical Approval

The protocol and all amendments were reviewed and approved by qualified institutional review boards/independent ethics committees before enrollment of participants in the study at each site. This study was conducted in accordance with the ethical principles of Good Clinical Practice, according to the International Conference on Harmonisation Guidelines. All aspects of the ethics review were conducted in accordance with the Declaration of Helsinki. Informed consent was obtained from each subject in writing before protocol-specific screening tests were performed.

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O’Shaughnessy, J., DeMichele, A., Ma, C.X. et al. A randomized, double-blind, phase 2 study of ruxolitinib or placebo in combination with capecitabine in patients with advanced HER2-negative breast cancer and elevated C-reactive protein, a marker of systemic inflammation. Breast Cancer Res Treat 170, 547–557 (2018). https://doi.org/10.1007/s10549-018-4770-6

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  • DOI: https://doi.org/10.1007/s10549-018-4770-6

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