Phase I/II trial of ruxolitinib in combination with trastuzumab in metastatic HER2 positive breast cancer

Matthew Kearney, Lauren Franks, Shing Lee, Amy Tiersten, Della F. Makower, Tessa Cigler, Prabhjot Mundi, Dow Chung Chi, Anupama Goel, Pam Klein, Eleni Andreopoulou, Joseph Sparano, Meghna Trivedi, Melissa Accordino, Andrea Califano, Dawn L. Hershman, Jose Silva, Kevin Kalinsky

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Preclinical data demonstrate STAT3 as an important regulator in HER2+ tumors, and disruption of the IL6-JAK2-STAT-S100A8/S100A9 signaling cascade reduces HER2+ cell viability. Ruxolitinib is an FDA approved inhibitor of JAK1 and JAK2. We performed a phase I/II trial investigating the safety and efficacy of the combination of trastuzumab and ruxolitinib in patients with trastuzumab-resistant metastatic HER2+ breast cancer. Methods: Patients with metastatic HER2+ breast cancer progressing on at least 2 lines of HER2-directed therapy were eligible. The phase I portion determined the tolerable dose of ruxolitinib in combination with trastuzumab. The primary objective of the phase II was to assess the progression free survival (PFS) of the combination of ruxolitinib plus trastuzumab compared to historical control. Results: Twenty-eight patients were enrolled, with a median number of prior therapies of 4.5. Ruxolitinib 25 mg twice daily was the recommended phase II dose with no dose limiting toxicities (DLTs). Of 26 evaluable patients in phase II, the median PFS was 8.3 weeks (95% CI 7.1, 13.9). Among the 14 patients with measurable disease, 1 patient had a partial response and 4 patients had stable disease. Most of the adverse events were hematologic. Conclusion: While well tolerated with a strong preclinical rationale, the combination of ruxolitinib and trastuzumab did not lead to an improvement in PFS compared to historical control in patients with trastuzumab-resistant metastatic HER2+ breast cancer.

Original languageEnglish (US)
Pages (from-to)177-185
Number of pages9
JournalBreast Cancer Research and Treatment
Volume189
Issue number1
DOIs
StatePublished - Aug 2021
Externally publishedYes

Keywords

  • Breast cancer
  • HER2 positive
  • JAK2
  • Ruxolitinib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Phase I/II trial of ruxolitinib in combination with trastuzumab in metastatic HER2 positive breast cancer'. Together they form a unique fingerprint.

Cite this