Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer

Joyce O'Shaughnessy, Beth Hellerstedt, Lee Schwartzberg, Denise A. Yardley, Michael A. Danso, Nicholas Robert, Paul Richards, Kathy Miller, Hope S. Rugo, Robert W. Carlson, Richard S. Finn, Marcus Neubauer, Mansoor Saleh, Jennifer M. Specht, Eric Charpentier, Ignacio Garcia-Ribas, Eric P. Winer

Research output: Contribution to journalArticle

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Abstract

Purpose: There is a lack of treatments providing survival benefit for patients with metastatic triple-negative breast cancer (mTNBC), with no standard of care. A randomized phase II trial showed significant benefit for gemcitabine, carboplatin, and iniparib (GCI) over gemcitabine and carboplatin (GC) in clinical benefit rate, response rate, progression-free survival (PFS), and overall survival (OS). Here, we formally compare the efficacy of these regimens in a phase III trial. Patients and Methods: Patients with stage IV/locally recurrent TNBC who had received no more than two previous chemotherapy regimens for mTNBC were randomly allocated to gemcitabine 1,000 mg/m2 and carboplatin area under the curve 2 (days 1 and 8) alone or GC plus iniparib 5.6 mg/kg (days 1, 4, 8, and 11) every 3 weeks. Random assignment was stratified by the number of prior chemotherapies. The coprimary end points were OS and PFS. Patients receiving GC could cross over to iniparib on progression. Results: Five hundred nineteen patients were randomly assigned (261 GCI; 258 GC). In the primary analysis, no statistically significant difference was observed for OS (hazard ratio [HR] = 0.88; 95% CI, 0.69 to 1.12; P = .28) nor PFS (HR = 0.79; 95% CI, 0.65 to 0.98; P = .027). An exploratory analysis showed that patients in the second-/third-line had improved OS (HR = 0.65; 95% CI, 0.46 to 0.91) and PFS (HR = 0.68; 95% CI, 0.50 to 0.92) with GCI. The safety profile for GCI was similar to GC. Conclusion: The trial did not meet the prespecified criteria for the coprimary end points of PFS and OS in the ITT population. The potential benefit with iniparib observed in second-/third-line subgroup warrants further evaluation.

Original languageEnglish
Pages (from-to)3840-3847
Number of pages8
JournalJournal of Clinical Oncology
Volume32
Issue number34
DOIs
StatePublished - Dec 1 2014

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gemcitabine
Triple Negative Breast Neoplasms
Carboplatin
Disease-Free Survival
Survival
iniparib
Drug Therapy
Standard of Care

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer. / O'Shaughnessy, Joyce; Hellerstedt, Beth; Schwartzberg, Lee; Yardley, Denise A.; Danso, Michael A.; Robert, Nicholas; Richards, Paul; Miller, Kathy; Rugo, Hope S.; Carlson, Robert W.; Finn, Richard S.; Neubauer, Marcus; Saleh, Mansoor; Specht, Jennifer M.; Charpentier, Eric; Garcia-Ribas, Ignacio; Winer, Eric P.

In: Journal of Clinical Oncology, Vol. 32, No. 34, 01.12.2014, p. 3840-3847.

Research output: Contribution to journalArticle

O'Shaughnessy, J, Hellerstedt, B, Schwartzberg, L, Yardley, DA, Danso, MA, Robert, N, Richards, P, Miller, K, Rugo, HS, Carlson, RW, Finn, RS, Neubauer, M, Saleh, M, Specht, JM, Charpentier, E, Garcia-Ribas, I & Winer, EP 2014, 'Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer', Journal of Clinical Oncology, vol. 32, no. 34, pp. 3840-3847. https://doi.org/10.1200/JCO.2014.55.2984
O'Shaughnessy, Joyce ; Hellerstedt, Beth ; Schwartzberg, Lee ; Yardley, Denise A. ; Danso, Michael A. ; Robert, Nicholas ; Richards, Paul ; Miller, Kathy ; Rugo, Hope S. ; Carlson, Robert W. ; Finn, Richard S. ; Neubauer, Marcus ; Saleh, Mansoor ; Specht, Jennifer M. ; Charpentier, Eric ; Garcia-Ribas, Ignacio ; Winer, Eric P. / Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer. In: Journal of Clinical Oncology. 2014 ; Vol. 32, No. 34. pp. 3840-3847.
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abstract = "Purpose: There is a lack of treatments providing survival benefit for patients with metastatic triple-negative breast cancer (mTNBC), with no standard of care. A randomized phase II trial showed significant benefit for gemcitabine, carboplatin, and iniparib (GCI) over gemcitabine and carboplatin (GC) in clinical benefit rate, response rate, progression-free survival (PFS), and overall survival (OS). Here, we formally compare the efficacy of these regimens in a phase III trial. Patients and Methods: Patients with stage IV/locally recurrent TNBC who had received no more than two previous chemotherapy regimens for mTNBC were randomly allocated to gemcitabine 1,000 mg/m2 and carboplatin area under the curve 2 (days 1 and 8) alone or GC plus iniparib 5.6 mg/kg (days 1, 4, 8, and 11) every 3 weeks. Random assignment was stratified by the number of prior chemotherapies. The coprimary end points were OS and PFS. Patients receiving GC could cross over to iniparib on progression. Results: Five hundred nineteen patients were randomly assigned (261 GCI; 258 GC). In the primary analysis, no statistically significant difference was observed for OS (hazard ratio [HR] = 0.88; 95{\%} CI, 0.69 to 1.12; P = .28) nor PFS (HR = 0.79; 95{\%} CI, 0.65 to 0.98; P = .027). An exploratory analysis showed that patients in the second-/third-line had improved OS (HR = 0.65; 95{\%} CI, 0.46 to 0.91) and PFS (HR = 0.68; 95{\%} CI, 0.50 to 0.92) with GCI. The safety profile for GCI was similar to GC. Conclusion: The trial did not meet the prespecified criteria for the coprimary end points of PFS and OS in the ITT population. The potential benefit with iniparib observed in second-/third-line subgroup warrants further evaluation.",
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T1 - Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer

AU - O'Shaughnessy, Joyce

AU - Hellerstedt, Beth

AU - Schwartzberg, Lee

AU - Yardley, Denise A.

AU - Danso, Michael A.

AU - Robert, Nicholas

AU - Richards, Paul

AU - Miller, Kathy

AU - Rugo, Hope S.

AU - Carlson, Robert W.

AU - Finn, Richard S.

AU - Neubauer, Marcus

AU - Saleh, Mansoor

AU - Specht, Jennifer M.

AU - Charpentier, Eric

AU - Garcia-Ribas, Ignacio

AU - Winer, Eric P.

PY - 2014/12/1

Y1 - 2014/12/1

N2 - Purpose: There is a lack of treatments providing survival benefit for patients with metastatic triple-negative breast cancer (mTNBC), with no standard of care. A randomized phase II trial showed significant benefit for gemcitabine, carboplatin, and iniparib (GCI) over gemcitabine and carboplatin (GC) in clinical benefit rate, response rate, progression-free survival (PFS), and overall survival (OS). Here, we formally compare the efficacy of these regimens in a phase III trial. Patients and Methods: Patients with stage IV/locally recurrent TNBC who had received no more than two previous chemotherapy regimens for mTNBC were randomly allocated to gemcitabine 1,000 mg/m2 and carboplatin area under the curve 2 (days 1 and 8) alone or GC plus iniparib 5.6 mg/kg (days 1, 4, 8, and 11) every 3 weeks. Random assignment was stratified by the number of prior chemotherapies. The coprimary end points were OS and PFS. Patients receiving GC could cross over to iniparib on progression. Results: Five hundred nineteen patients were randomly assigned (261 GCI; 258 GC). In the primary analysis, no statistically significant difference was observed for OS (hazard ratio [HR] = 0.88; 95% CI, 0.69 to 1.12; P = .28) nor PFS (HR = 0.79; 95% CI, 0.65 to 0.98; P = .027). An exploratory analysis showed that patients in the second-/third-line had improved OS (HR = 0.65; 95% CI, 0.46 to 0.91) and PFS (HR = 0.68; 95% CI, 0.50 to 0.92) with GCI. The safety profile for GCI was similar to GC. Conclusion: The trial did not meet the prespecified criteria for the coprimary end points of PFS and OS in the ITT population. The potential benefit with iniparib observed in second-/third-line subgroup warrants further evaluation.

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