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Clinical Trial
. 2018 Oct;18(5):387-394.
doi: 10.1016/j.clbc.2018.03.010. Epub 2018 Mar 15.

Phase II Study of Paclitaxel and Dasatinib in Metastatic Breast Cancer

Patrick G Morris  1 , Selene Rota  2 , Karen Cadoo  3 , Stephen Zamora  3 , Sujata Patil  3 , Gabriella D'Andrea  3 , Theresa Gilewski  3 , Jacqueline Bromberg  3 , Chau Dang  3 , Maura Dickler  3 , Shanu Modi  3 , Andrew D Seidman  3 , Nancy Sklarin  3 , Larry Norton  3 , Clifford A Hudis  3 , Monica N Fornier  4
Affiliations
Clinical Trial

Phase II Study of Paclitaxel and Dasatinib in Metastatic Breast Cancer

Patrick G Morris et al. Clin Breast Cancer. 2018 Oct.

Abstract

Background: Overexpression and activation of tyrosine kinase Src has been linked to breast carcinogenesis and bone metastases. We showed the feasibility of combining the SRC inhibitor dasatinib with weekly paclitaxel in patients with metastatic breast cancer (MBC) and herein report the subsequent phase II trial.

Patients and methods: Patients had received ≤ 2 chemotherapy regimens for measurable, HER2-negative MBC. Patients received paclitaxel and dasatinib (120 mg daily) and were assessed according to Response Evaluation Criteria in Solid Tumors for overall response rate (ORR), the primary end point. Secondary end points included progression-free survival (PFS) and overall survival (OS). A 30% ORR (n = 55) was deemed worthy of further investigation. Exploratory biomarkers included N-telopeptide (NTX) and plasma vascular epidermal growth factor (VEGF) receptor 2 as predictors of clinical benefit.

Results: From March 2010 to March 2014, 40 patients, including 2 men enrolled. The study was stopped early because of slow accrual. Overall, 32 patients (80%) had estrogen receptor-positive tumors and 23 (58%) had previously received taxanes. Of the 35 assessable patients, 1 (3%) had complete response and 7 (20%) partial response, resulting in an ORR of 23%. The median PFS and OS was 5.2 (95% confidence interval [CI], 2.9-9.9) and 20.6 (95% CI, 12.9-25.2) months, respectively. As expected, fatigue (75%), neuropathy (65%), and diarrhea (50%) were common side effects, but were generally low-grade. Median baseline NTX was similar in patients who had clinical benefit (8.2 nmol BCE) and no clinical benefit (10.9 nmol BCE). Similarly, median baseline VEGF levels were similar between the 2 groups; 93.0 pg/mL versus 83.0 pg/mL.

Conclusion: This phase II study of dasatinib and paclitaxel was stopped early because of slow accrual but showed some clinical activity. Further study is not planned.

Keywords: Advanced breast cancer; Dasatinib; Metastatic breast cancer; Paclitaxel; SRC.

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Figures

Figure 1.
Figure 1.
Consort Diagram
Figure 2.
Figure 2.. Best Response of Target Lesions in Evaluable Patients (n=35)
P= prior therapy with paclitaxel Green: patients with triple negative breast cancer Blue: patients with ER positive disease *Best Response = Progression of Disease (due to development of new lesions or progression of non-measurable disease)
Figure 3
Figure 3
Progression Free Survival (A) and Overall Survival (B)
Figure 3
Figure 3
Progression Free Survival (A) and Overall Survival (B)
Figure 4
Figure 4. A, B, C Predictive Biomarkers of Benefit from Paclitaxel and Dasatinib
NTX; Collagen Type IV or N-telopeptide, VEGF; vascular epidermal growth factor receptor 2 CTC; circulating tumor cells Box and Whisker plots comparing median (horizontal line), interquartile range (shaded box) and range
Figure 4
Figure 4. A, B, C Predictive Biomarkers of Benefit from Paclitaxel and Dasatinib
NTX; Collagen Type IV or N-telopeptide, VEGF; vascular epidermal growth factor receptor 2 CTC; circulating tumor cells Box and Whisker plots comparing median (horizontal line), interquartile range (shaded box) and range
See this image and copyright information in PMC

Comment in

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