A phase 2 trial of dasatinib in patients with advanced HER2-positive and/or hormone receptor-positive breast cancer

Erica L. Mayer, Jean Francois Baurain, Joseph A. Sparano, Lewis Strauss, Mario Campone, Pierre Fumoleau, Hope Rugo, Ahmad Awada, Oumar Sy, Antonio Llombart-Cussac

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Purpose: SRC-family kinases (SFK) are involved in numerous oncogenic signaling pathways. A phase 2 trial of dasatinib, a potent oral tyrosine kinase inhibitor of SFKs, was carried out in patients with human epidermal growth factor receptor 2-positive (HER2+) and/or hormone receptor-positive (HR+) advanced breast cancer. Experimental Design: Patients with measurable tumors and progression after chemotherapy and HER2 and/or HR-targeted agents in adjuvant or metastatic settings (maximum of two prior metastatic setting regimens) received twice daily dasatinib. Primary endpoint was Response Evaluation Criteria in Solid Tumors-defined response rate. Secondary endpoints included toxicity and limited pharmacokinetics. Results: Seventy patients (55 years median age) were treated, 83% of HER2+ patients had received prior HER2-directed therapy, and 61% of HR+ patients had received prior endocrine therapy in the advanced setting. Dasatinib starting dose was reduced from 100 to 70 mg twice daily to limit toxicity. Median therapy duration was 1.8 months in both dose groups and most discontinuations were due to progression. Of 69 evaluable patients, three had confirmed partial responses and six had stable disease for 16 weeks or more (disease control rate = 13.0%); all nine of these tumors were HR+ (two were also HER2+). The most common drug-related toxicities were gastrointestinal complaints, headache, asthenia, and pleural effusion. Grade 3-4 toxicity occurred in 37% of patients and was comparable between doses; drug-related serious adverse events were less frequent with 70 mg twice daily than 100 mg twice daily. Conclusion: Limited single-agent activity was observed with dasatinib in patients with advanced HR+ breast cancer.

Original languageEnglish (US)
Pages (from-to)6897-6904
Number of pages8
JournalClinical Cancer Research
Volume17
Issue number21
DOIs
StatePublished - Nov 1 2011

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Hormones
Breast Neoplasms
Asthenia
Dasatinib
Pleural Effusion
Drug-Related Side Effects and Adverse Reactions
Protein-Tyrosine Kinases
Headache
Neoplasms
Research Design
Phosphotransferases
Therapeutics
Pharmacokinetics
Drug Therapy
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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A phase 2 trial of dasatinib in patients with advanced HER2-positive and/or hormone receptor-positive breast cancer. / Mayer, Erica L.; Baurain, Jean Francois; Sparano, Joseph A.; Strauss, Lewis; Campone, Mario; Fumoleau, Pierre; Rugo, Hope; Awada, Ahmad; Sy, Oumar; Llombart-Cussac, Antonio.

In: Clinical Cancer Research, Vol. 17, No. 21, 01.11.2011, p. 6897-6904.

Research output: Contribution to journalArticle

Mayer, EL, Baurain, JF, Sparano, JA, Strauss, L, Campone, M, Fumoleau, P, Rugo, H, Awada, A, Sy, O & Llombart-Cussac, A 2011, 'A phase 2 trial of dasatinib in patients with advanced HER2-positive and/or hormone receptor-positive breast cancer', Clinical Cancer Research, vol. 17, no. 21, pp. 6897-6904. https://doi.org/10.1158/1078-0432.CCR-11-0070
Mayer, Erica L. ; Baurain, Jean Francois ; Sparano, Joseph A. ; Strauss, Lewis ; Campone, Mario ; Fumoleau, Pierre ; Rugo, Hope ; Awada, Ahmad ; Sy, Oumar ; Llombart-Cussac, Antonio. / A phase 2 trial of dasatinib in patients with advanced HER2-positive and/or hormone receptor-positive breast cancer. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 21. pp. 6897-6904.
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AU - Strauss, Lewis

AU - Campone, Mario

AU - Fumoleau, Pierre

AU - Rugo, Hope

AU - Awada, Ahmad

AU - Sy, Oumar

AU - Llombart-Cussac, Antonio

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