Bosutinib in combination with the aromatase inhibitor letrozole: A phase II trial in postmenopausalwomen evaluating first-line endocrine therapy in locally advanced or metastatic hormone receptor-positive/HER2-negative breast cancer

Beverly Moy, Patrick Neven, Fabienne Lebrun, Meritxell Bellet, Binghe Xu, Tomasz Sarosiek, Louis Chow, Paul Goss, Charles Zacharchuk, Eric Leip, Kathleen Turnbull, Nathalie Bardy-Bouxin, Ladan Duvillié, I. Láng

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background. Endocrine therapy resistance in hormone receptorpositive (HR+) breast cancer (BC) may involve crosstalk between HRs and growth factor signaling pathways. We evaluated bosutinib, a dual Src/Abl tyrosine kinase inhibitor that has previously demonstrated some antitumor activity in BC, plus letrozole as first-line endocrine therapy in locally advanced or metastatic HR+/HER2- BC. Methods. Sixteen postmenopausal women were enrolled in a phase II study evaluating the safety/efficacy of bosutinib plus letrozole. In the single-arm safety/dose-confirming lead-in (part 1), patients received oral bosutinib at 400 mg/day plus letrozole at 2.5mg/day; adverse events (AEs)anddose-limiting toxicities (DLTs) were monitored, and initial efficacy was assessed. A randomized efficacy/safety phase (part 2) was planned to evaluate the combination versus letrozole monotherapy. Results. Fifteen of 16 subjects experienced treatment-related AEs, most commonly diarrhea (69%). Treatment-related hepatotoxicity AEs (primarily alanine aminotransferase [ALT] or aspartate aminotransferase [AST] elevations) occurred in 6 of 16 patients (38%). Four of 15 evaluable patients (27%) experienced a DLT (grade 3/4 ALT/AST elevations, n = 2; grade 3 rash, n = 1; grade 3 diarrhea or vomiting, n = 1), including 1 Hy's law hepatotoxicity case. All DLTs resolved following treatment discontinuation. One patient achieved confirmed partial response; one had stable disease for >24 weeks. Study termination occurred before part 2. Conclusion. The unfavorable risk-benefit ratio did not warrant further investigation of bosutinib plus letrozole.

Original languageEnglish
Pages (from-to)348-349
Number of pages2
JournalOncologist
Volume19
Issue number4
DOIs
Publication statusPublished - 2014

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letrozole
Aromatase Inhibitors
Hormones
Breast Neoplasms
Aspartate Aminotransferases
Alanine Transaminase
Safety
Diarrhea
Therapeutics
src-Family Kinases
Exanthema
Vomiting
Intercellular Signaling Peptides and Proteins
Odds Ratio
bosutinib

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Bosutinib in combination with the aromatase inhibitor letrozole : A phase II trial in postmenopausalwomen evaluating first-line endocrine therapy in locally advanced or metastatic hormone receptor-positive/HER2-negative breast cancer. / Moy, Beverly; Neven, Patrick; Lebrun, Fabienne; Bellet, Meritxell; Xu, Binghe; Sarosiek, Tomasz; Chow, Louis; Goss, Paul; Zacharchuk, Charles; Leip, Eric; Turnbull, Kathleen; Bardy-Bouxin, Nathalie; Duvillié, Ladan; Láng, I.

In: Oncologist, Vol. 19, No. 4, 2014, p. 348-349.

Research output: Contribution to journalArticle

Moy, Beverly ; Neven, Patrick ; Lebrun, Fabienne ; Bellet, Meritxell ; Xu, Binghe ; Sarosiek, Tomasz ; Chow, Louis ; Goss, Paul ; Zacharchuk, Charles ; Leip, Eric ; Turnbull, Kathleen ; Bardy-Bouxin, Nathalie ; Duvillié, Ladan ; Láng, I. / Bosutinib in combination with the aromatase inhibitor letrozole : A phase II trial in postmenopausalwomen evaluating first-line endocrine therapy in locally advanced or metastatic hormone receptor-positive/HER2-negative breast cancer. In: Oncologist. 2014 ; Vol. 19, No. 4. pp. 348-349.
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abstract = "Background. Endocrine therapy resistance in hormone receptorpositive (HR+) breast cancer (BC) may involve crosstalk between HRs and growth factor signaling pathways. We evaluated bosutinib, a dual Src/Abl tyrosine kinase inhibitor that has previously demonstrated some antitumor activity in BC, plus letrozole as first-line endocrine therapy in locally advanced or metastatic HR+/HER2- BC. Methods. Sixteen postmenopausal women were enrolled in a phase II study evaluating the safety/efficacy of bosutinib plus letrozole. In the single-arm safety/dose-confirming lead-in (part 1), patients received oral bosutinib at 400 mg/day plus letrozole at 2.5mg/day; adverse events (AEs)anddose-limiting toxicities (DLTs) were monitored, and initial efficacy was assessed. A randomized efficacy/safety phase (part 2) was planned to evaluate the combination versus letrozole monotherapy. Results. Fifteen of 16 subjects experienced treatment-related AEs, most commonly diarrhea (69{\%}). Treatment-related hepatotoxicity AEs (primarily alanine aminotransferase [ALT] or aspartate aminotransferase [AST] elevations) occurred in 6 of 16 patients (38{\%}). Four of 15 evaluable patients (27{\%}) experienced a DLT (grade 3/4 ALT/AST elevations, n = 2; grade 3 rash, n = 1; grade 3 diarrhea or vomiting, n = 1), including 1 Hy's law hepatotoxicity case. All DLTs resolved following treatment discontinuation. One patient achieved confirmed partial response; one had stable disease for >24 weeks. Study termination occurred before part 2. Conclusion. The unfavorable risk-benefit ratio did not warrant further investigation of bosutinib plus letrozole.",
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AU - Moy, Beverly

AU - Neven, Patrick

AU - Lebrun, Fabienne

AU - Bellet, Meritxell

AU - Xu, Binghe

AU - Sarosiek, Tomasz

AU - Chow, Louis

AU - Goss, Paul

AU - Zacharchuk, Charles

AU - Leip, Eric

AU - Turnbull, Kathleen

AU - Bardy-Bouxin, Nathalie

AU - Duvillié, Ladan

AU - Láng, I.

PY - 2014

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N2 - Background. Endocrine therapy resistance in hormone receptorpositive (HR+) breast cancer (BC) may involve crosstalk between HRs and growth factor signaling pathways. We evaluated bosutinib, a dual Src/Abl tyrosine kinase inhibitor that has previously demonstrated some antitumor activity in BC, plus letrozole as first-line endocrine therapy in locally advanced or metastatic HR+/HER2- BC. Methods. Sixteen postmenopausal women were enrolled in a phase II study evaluating the safety/efficacy of bosutinib plus letrozole. In the single-arm safety/dose-confirming lead-in (part 1), patients received oral bosutinib at 400 mg/day plus letrozole at 2.5mg/day; adverse events (AEs)anddose-limiting toxicities (DLTs) were monitored, and initial efficacy was assessed. A randomized efficacy/safety phase (part 2) was planned to evaluate the combination versus letrozole monotherapy. Results. Fifteen of 16 subjects experienced treatment-related AEs, most commonly diarrhea (69%). Treatment-related hepatotoxicity AEs (primarily alanine aminotransferase [ALT] or aspartate aminotransferase [AST] elevations) occurred in 6 of 16 patients (38%). Four of 15 evaluable patients (27%) experienced a DLT (grade 3/4 ALT/AST elevations, n = 2; grade 3 rash, n = 1; grade 3 diarrhea or vomiting, n = 1), including 1 Hy's law hepatotoxicity case. All DLTs resolved following treatment discontinuation. One patient achieved confirmed partial response; one had stable disease for >24 weeks. Study termination occurred before part 2. Conclusion. The unfavorable risk-benefit ratio did not warrant further investigation of bosutinib plus letrozole.

AB - Background. Endocrine therapy resistance in hormone receptorpositive (HR+) breast cancer (BC) may involve crosstalk between HRs and growth factor signaling pathways. We evaluated bosutinib, a dual Src/Abl tyrosine kinase inhibitor that has previously demonstrated some antitumor activity in BC, plus letrozole as first-line endocrine therapy in locally advanced or metastatic HR+/HER2- BC. Methods. Sixteen postmenopausal women were enrolled in a phase II study evaluating the safety/efficacy of bosutinib plus letrozole. In the single-arm safety/dose-confirming lead-in (part 1), patients received oral bosutinib at 400 mg/day plus letrozole at 2.5mg/day; adverse events (AEs)anddose-limiting toxicities (DLTs) were monitored, and initial efficacy was assessed. A randomized efficacy/safety phase (part 2) was planned to evaluate the combination versus letrozole monotherapy. Results. Fifteen of 16 subjects experienced treatment-related AEs, most commonly diarrhea (69%). Treatment-related hepatotoxicity AEs (primarily alanine aminotransferase [ALT] or aspartate aminotransferase [AST] elevations) occurred in 6 of 16 patients (38%). Four of 15 evaluable patients (27%) experienced a DLT (grade 3/4 ALT/AST elevations, n = 2; grade 3 rash, n = 1; grade 3 diarrhea or vomiting, n = 1), including 1 Hy's law hepatotoxicity case. All DLTs resolved following treatment discontinuation. One patient achieved confirmed partial response; one had stable disease for >24 weeks. Study termination occurred before part 2. Conclusion. The unfavorable risk-benefit ratio did not warrant further investigation of bosutinib plus letrozole.

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