Predictive role of hand–foot syndrome in patients receiving first-line capecitabine plus bevacizumab for HER2-negative metastatic breast cancer

Christoph Zielinski, I. Láng, Semir Beslija, Z. Kahán, Moshe J. Inbar, Salomon M. Stemmer, Rodica Anghel, Damir Vrbanec, Diethelm Messinger, Thomas Brodowicz

Research output: Contribution to journalArticle

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Abstract

Background:Correlations between development of hand–foot syndrome (HFS) and efficacy in patients receiving capecitabine (CAP)-containing therapy are reported in the literature. We explored the relationship between HFS and efficacy in patients receiving CAP plus bevacizumab (BEV) in the TURANDOT randomised phase III trial.Methods:Patients with HER2-negative locally recurrent/metastatic breast cancer (LR/mBC) who had received no prior chemotherapy for LR/mBC were randomised to BEV plus paclitaxel or BEV–CAP until disease progression or unacceptable toxicity. This analysis included patients randomised to BEV–CAP who received ⩾1 CAP dose. Potential associations between HFS and both overall survival (OS; primary end point) and progression-free survival (PFS; secondary end point) were explored using Cox proportional hazards analyses with HFS as a time-dependent covariate (to avoid overestimating the effect of HFS on efficacy). Landmark analyses were also performed.Results:Among 277 patients treated with BEV–CAP, 154 (56%) developed HFS. In multivariate analyses, risk of progression or death was reduced by 44% after the occurrence of HFS; risk of death was reduced by 56%. The magnitude of effect on OS increased with increasing HFS grade. In patients developing HFS within the first 3 months, median PFS from the 3-month landmark was 10.0 months vs 6.2 months in patients without HFS. Two-year OS rates were 63% and 44%, respectively.Conclusions:This exploratory analysis indicates that HFS occurrence is a strong predictor of prolonged PFS and OS in patients receiving BEV–CAP for LR/mBC. Early appearance of HFS may help motivate patients to continue therapy.British Journal of Cancer advance online publication, 10 December 2015; doi:10.1038/bjc.2015.419 www.bjcancer.com.

Original languageEnglish
JournalBritish Journal of Cancer
DOIs
Publication statusAccepted/In press - Dec 10 2015

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Breast Neoplasms
Bevacizumab
Capecitabine
Paclitaxel
Disease-Free Survival
Disease Progression
Publications
Multivariate Analysis
Drug Therapy
Survival
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Predictive role of hand–foot syndrome in patients receiving first-line capecitabine plus bevacizumab for HER2-negative metastatic breast cancer. / Zielinski, Christoph; Láng, I.; Beslija, Semir; Kahán, Z.; Inbar, Moshe J.; Stemmer, Salomon M.; Anghel, Rodica; Vrbanec, Damir; Messinger, Diethelm; Brodowicz, Thomas.

In: British Journal of Cancer, 10.12.2015.

Research output: Contribution to journalArticle

Zielinski, Christoph ; Láng, I. ; Beslija, Semir ; Kahán, Z. ; Inbar, Moshe J. ; Stemmer, Salomon M. ; Anghel, Rodica ; Vrbanec, Damir ; Messinger, Diethelm ; Brodowicz, Thomas. / Predictive role of hand–foot syndrome in patients receiving first-line capecitabine plus bevacizumab for HER2-negative metastatic breast cancer. In: British Journal of Cancer. 2015.
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abstract = "Background:Correlations between development of hand–foot syndrome (HFS) and efficacy in patients receiving capecitabine (CAP)-containing therapy are reported in the literature. We explored the relationship between HFS and efficacy in patients receiving CAP plus bevacizumab (BEV) in the TURANDOT randomised phase III trial.Methods:Patients with HER2-negative locally recurrent/metastatic breast cancer (LR/mBC) who had received no prior chemotherapy for LR/mBC were randomised to BEV plus paclitaxel or BEV–CAP until disease progression or unacceptable toxicity. This analysis included patients randomised to BEV–CAP who received ⩾1 CAP dose. Potential associations between HFS and both overall survival (OS; primary end point) and progression-free survival (PFS; secondary end point) were explored using Cox proportional hazards analyses with HFS as a time-dependent covariate (to avoid overestimating the effect of HFS on efficacy). Landmark analyses were also performed.Results:Among 277 patients treated with BEV–CAP, 154 (56{\%}) developed HFS. In multivariate analyses, risk of progression or death was reduced by 44{\%} after the occurrence of HFS; risk of death was reduced by 56{\%}. The magnitude of effect on OS increased with increasing HFS grade. In patients developing HFS within the first 3 months, median PFS from the 3-month landmark was 10.0 months vs 6.2 months in patients without HFS. Two-year OS rates were 63{\%} and 44{\%}, respectively.Conclusions:This exploratory analysis indicates that HFS occurrence is a strong predictor of prolonged PFS and OS in patients receiving BEV–CAP for LR/mBC. Early appearance of HFS may help motivate patients to continue therapy.British Journal of Cancer advance online publication, 10 December 2015; doi:10.1038/bjc.2015.419 www.bjcancer.com.",
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AU - Kahán, Z.

AU - Inbar, Moshe J.

AU - Stemmer, Salomon M.

AU - Anghel, Rodica

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AU - Messinger, Diethelm

AU - Brodowicz, Thomas

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AB - Background:Correlations between development of hand–foot syndrome (HFS) and efficacy in patients receiving capecitabine (CAP)-containing therapy are reported in the literature. We explored the relationship between HFS and efficacy in patients receiving CAP plus bevacizumab (BEV) in the TURANDOT randomised phase III trial.Methods:Patients with HER2-negative locally recurrent/metastatic breast cancer (LR/mBC) who had received no prior chemotherapy for LR/mBC were randomised to BEV plus paclitaxel or BEV–CAP until disease progression or unacceptable toxicity. This analysis included patients randomised to BEV–CAP who received ⩾1 CAP dose. Potential associations between HFS and both overall survival (OS; primary end point) and progression-free survival (PFS; secondary end point) were explored using Cox proportional hazards analyses with HFS as a time-dependent covariate (to avoid overestimating the effect of HFS on efficacy). Landmark analyses were also performed.Results:Among 277 patients treated with BEV–CAP, 154 (56%) developed HFS. In multivariate analyses, risk of progression or death was reduced by 44% after the occurrence of HFS; risk of death was reduced by 56%. The magnitude of effect on OS increased with increasing HFS grade. In patients developing HFS within the first 3 months, median PFS from the 3-month landmark was 10.0 months vs 6.2 months in patients without HFS. Two-year OS rates were 63% and 44%, respectively.Conclusions:This exploratory analysis indicates that HFS occurrence is a strong predictor of prolonged PFS and OS in patients receiving BEV–CAP for LR/mBC. Early appearance of HFS may help motivate patients to continue therapy.British Journal of Cancer advance online publication, 10 December 2015; doi:10.1038/bjc.2015.419 www.bjcancer.com.

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