Maintenance of clinical efficacy after dose reduction of ixabepilone plus capecitabine in patients with anthracycline- and taxane-resistant metastatic breast cancer

A retrospective analysis of pooled data from 2 phase III randomized clinical trials

Vicente Valero, Eduard Vrdoljak, Binghe Xu, Eva Thomas, Henry Gómez, Alexey Manikhas, Carlos Medina, Rubi Khaw Li, Jungsil Ro, Linda Bosserman, Linda Vahdat, Pralay Mukhopadhyay, Diane Opatt, Joseph A. Sparano

Research output: Contribution to journalArticle

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Abstract

Background: This retrospective analysis aimed to determine whether early dose reduction impacts the efficacy of ixabepilone plus capecitabine in women with metastatic breast cancer (MBC). Patients and Methods: In 2 phase III trials, patients (N = 1973) with anthracycline/taxane-pretreated MBC were randomized to receive ixabepilone 40 mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice daily (BID) on days 1 to 14 or single-agent capecitabine 1250 mg/m2 BID on days 1 to 14 of a 3-week course. Because of the similar design and populations, data from trials were pooled to evaluate efficacy of the combination regimen among women who did or did not undergo ixabepilone dose reduction during the first 4 courses. To adjust for bias resulting from selecting patients with inherently better outcome based on longer treatment durations, these analyses were restricted to patients who received < 4 courses of ixabepilone. Results: The pooled cohort included 566 patients with measurable disease who were evaluable for efficacy. Patients who had early dose reduction showed similar objective response rates (ORRs) and progression-free survival (PFS) as did those with no/late dose reduction. ORRs were 62.6% (95% confidence interval [CI], 55.8%-69.0%) and 55.3% (95% CI, 49.9%-60.6%), respectively; median PFS was 7.2 months (95% CI, 6.6-8.0) and 7.0 months (95% CI, 6.5-7.5), respectively (hazard ratio = 0.98; 95% CI, 0.83-1.17). Conclusion: These data suggest that early ixabepilone dose reduction did not affect the overall efficacy of ixabepilone plus capecitabine in patients with MBC who received < 4 courses of treatment. By making appropriate dose reductions, ixabepilone-related toxicities can be minimized while maintaining clinical efficacy.

Original languageEnglish (US)
Pages (from-to)240-246
Number of pages7
JournalClinical Breast Cancer
Volume12
Issue number4
DOIs
StatePublished - 2012

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Phase III Clinical Trials
Anthracyclines
Randomized Controlled Trials
Maintenance
Breast Neoplasms
Confidence Intervals
Disease-Free Survival
Capecitabine
ixabepilone
taxane
Therapeutics
Population

Keywords

  • Epothilones
  • Microtubules
  • Minimizing toxicity
  • Treatment tolerability

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Maintenance of clinical efficacy after dose reduction of ixabepilone plus capecitabine in patients with anthracycline- and taxane-resistant metastatic breast cancer : A retrospective analysis of pooled data from 2 phase III randomized clinical trials. / Valero, Vicente; Vrdoljak, Eduard; Xu, Binghe; Thomas, Eva; Gómez, Henry; Manikhas, Alexey; Medina, Carlos; Li, Rubi Khaw; Ro, Jungsil; Bosserman, Linda; Vahdat, Linda; Mukhopadhyay, Pralay; Opatt, Diane; Sparano, Joseph A.

In: Clinical Breast Cancer, Vol. 12, No. 4, 2012, p. 240-246.

Research output: Contribution to journalArticle

Valero, Vicente ; Vrdoljak, Eduard ; Xu, Binghe ; Thomas, Eva ; Gómez, Henry ; Manikhas, Alexey ; Medina, Carlos ; Li, Rubi Khaw ; Ro, Jungsil ; Bosserman, Linda ; Vahdat, Linda ; Mukhopadhyay, Pralay ; Opatt, Diane ; Sparano, Joseph A. / Maintenance of clinical efficacy after dose reduction of ixabepilone plus capecitabine in patients with anthracycline- and taxane-resistant metastatic breast cancer : A retrospective analysis of pooled data from 2 phase III randomized clinical trials. In: Clinical Breast Cancer. 2012 ; Vol. 12, No. 4. pp. 240-246.
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abstract = "Background: This retrospective analysis aimed to determine whether early dose reduction impacts the efficacy of ixabepilone plus capecitabine in women with metastatic breast cancer (MBC). Patients and Methods: In 2 phase III trials, patients (N = 1973) with anthracycline/taxane-pretreated MBC were randomized to receive ixabepilone 40 mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice daily (BID) on days 1 to 14 or single-agent capecitabine 1250 mg/m2 BID on days 1 to 14 of a 3-week course. Because of the similar design and populations, data from trials were pooled to evaluate efficacy of the combination regimen among women who did or did not undergo ixabepilone dose reduction during the first 4 courses. To adjust for bias resulting from selecting patients with inherently better outcome based on longer treatment durations, these analyses were restricted to patients who received < 4 courses of ixabepilone. Results: The pooled cohort included 566 patients with measurable disease who were evaluable for efficacy. Patients who had early dose reduction showed similar objective response rates (ORRs) and progression-free survival (PFS) as did those with no/late dose reduction. ORRs were 62.6{\%} (95{\%} confidence interval [CI], 55.8{\%}-69.0{\%}) and 55.3{\%} (95{\%} CI, 49.9{\%}-60.6{\%}), respectively; median PFS was 7.2 months (95{\%} CI, 6.6-8.0) and 7.0 months (95{\%} CI, 6.5-7.5), respectively (hazard ratio = 0.98; 95{\%} CI, 0.83-1.17). Conclusion: These data suggest that early ixabepilone dose reduction did not affect the overall efficacy of ixabepilone plus capecitabine in patients with MBC who received < 4 courses of treatment. By making appropriate dose reductions, ixabepilone-related toxicities can be minimized while maintaining clinical efficacy.",
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AU - Vrdoljak, Eduard

AU - Xu, Binghe

AU - Thomas, Eva

AU - Gómez, Henry

AU - Manikhas, Alexey

AU - Medina, Carlos

AU - Li, Rubi Khaw

AU - Ro, Jungsil

AU - Bosserman, Linda

AU - Vahdat, Linda

AU - Mukhopadhyay, Pralay

AU - Opatt, Diane

AU - Sparano, Joseph A.

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N2 - Background: This retrospective analysis aimed to determine whether early dose reduction impacts the efficacy of ixabepilone plus capecitabine in women with metastatic breast cancer (MBC). Patients and Methods: In 2 phase III trials, patients (N = 1973) with anthracycline/taxane-pretreated MBC were randomized to receive ixabepilone 40 mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice daily (BID) on days 1 to 14 or single-agent capecitabine 1250 mg/m2 BID on days 1 to 14 of a 3-week course. Because of the similar design and populations, data from trials were pooled to evaluate efficacy of the combination regimen among women who did or did not undergo ixabepilone dose reduction during the first 4 courses. To adjust for bias resulting from selecting patients with inherently better outcome based on longer treatment durations, these analyses were restricted to patients who received < 4 courses of ixabepilone. Results: The pooled cohort included 566 patients with measurable disease who were evaluable for efficacy. Patients who had early dose reduction showed similar objective response rates (ORRs) and progression-free survival (PFS) as did those with no/late dose reduction. ORRs were 62.6% (95% confidence interval [CI], 55.8%-69.0%) and 55.3% (95% CI, 49.9%-60.6%), respectively; median PFS was 7.2 months (95% CI, 6.6-8.0) and 7.0 months (95% CI, 6.5-7.5), respectively (hazard ratio = 0.98; 95% CI, 0.83-1.17). Conclusion: These data suggest that early ixabepilone dose reduction did not affect the overall efficacy of ixabepilone plus capecitabine in patients with MBC who received < 4 courses of treatment. By making appropriate dose reductions, ixabepilone-related toxicities can be minimized while maintaining clinical efficacy.

AB - Background: This retrospective analysis aimed to determine whether early dose reduction impacts the efficacy of ixabepilone plus capecitabine in women with metastatic breast cancer (MBC). Patients and Methods: In 2 phase III trials, patients (N = 1973) with anthracycline/taxane-pretreated MBC were randomized to receive ixabepilone 40 mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice daily (BID) on days 1 to 14 or single-agent capecitabine 1250 mg/m2 BID on days 1 to 14 of a 3-week course. Because of the similar design and populations, data from trials were pooled to evaluate efficacy of the combination regimen among women who did or did not undergo ixabepilone dose reduction during the first 4 courses. To adjust for bias resulting from selecting patients with inherently better outcome based on longer treatment durations, these analyses were restricted to patients who received < 4 courses of ixabepilone. Results: The pooled cohort included 566 patients with measurable disease who were evaluable for efficacy. Patients who had early dose reduction showed similar objective response rates (ORRs) and progression-free survival (PFS) as did those with no/late dose reduction. ORRs were 62.6% (95% confidence interval [CI], 55.8%-69.0%) and 55.3% (95% CI, 49.9%-60.6%), respectively; median PFS was 7.2 months (95% CI, 6.6-8.0) and 7.0 months (95% CI, 6.5-7.5), respectively (hazard ratio = 0.98; 95% CI, 0.83-1.17). Conclusion: These data suggest that early ixabepilone dose reduction did not affect the overall efficacy of ixabepilone plus capecitabine in patients with MBC who received < 4 courses of treatment. By making appropriate dose reductions, ixabepilone-related toxicities can be minimized while maintaining clinical efficacy.

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KW - Microtubules

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KW - Treatment tolerability

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