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Phase I study of JAK1/2 inhibitor ruxolitinib with weekly paclitaxel for the treatment of HER2-negative metastatic breast cancer.
- Source :
- Cancer Chemotherapy & Pharmacology; May2021, Vol. 87 Issue 5, p673-679, 7p
- Publication Year :
- 2021
-
Abstract
- Purpose: Preclinical studies support the JAK2–STAT3 signaling pathway as a key driver in CD44+ CD24− "stem-cell-like" breast cancer cells. Ruxolitinib is an orally bioavailable JAK1/2 inhibitor. We aimed to identify the recommended phase 2 dose (RP2D) of ruxolitinib in combination with paclitaxel in patients with HER2-negative metastatic breast cancer (MBC). Methods: Eligible patients had HER2-negative MBC and had received ≤ 3 chemotherapy regimens for advanced disease. Patients received oral ruxolitinib (10–25 mg bid) in a 3 + 3 dose escalation design in combination with weekly paclitaxel 80 mg/m<superscript>2</superscript> in a 3-week cycle. The primary objective was to determine the maximum tolerated dose (MTD) and the RP2D. Results: Nineteen patients received protocol therapy (mean age 52 years). Eight (42%) had triple-negative breast cancer and 11 (58%) had hormone receptor-positive disease; 12 (63%) had visceral disease. Ten (53%) patients had not received prior treatment for advanced disease. Patients received a median number of 5 cycles of combination therapy (range 1–12) and five patients continued single-agent ruxolitinib. The MTD of ruxolitinib was 25 mg bid when combined with paclitaxel, and the RP2D for the combination was 15 mg bid. Thirteen (68%) patients required dose reductions or holds. Most frequent toxicities reported of any grade were neutropenia (50%) and anemia (33%). There were no grade 4/5 toxicities attributed to study drug. Four (21%) patients had PR, 12 (63%) had SD and three (16%) had PD as their best response. Conclusion: The combination of ruxolitinib and weekly paclitaxel was well tolerated with evidence of clinical activity. Further analysis of this combination is ongoing (NCT02041429). Trial registration: NCT02041429. Date of registration: January 22, 2014. [ABSTRACT FROM AUTHOR]
- Subjects :
- PACLITAXEL
METASTATIC breast cancer
TRIPLE-negative breast cancer
Subjects
Details
- Language :
- English
- ISSN :
- 03445704
- Volume :
- 87
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Cancer Chemotherapy & Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 149694287
- Full Text :
- https://doi.org/10.1007/s00280-021-04245-x