Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer

A systematic review and meta-analysis

F. Poggio, M. Bruzzone, M. Ceppi, N. F. Pondé, G. La Valle, L. Del Mastro, E. De Azambuja, Matteo Lambertini

Research output: Contribution to journalReview article

24 Citations (Scopus)

Abstract

Background: The role of platinum-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients is highly controversial and it is not endorsed by current guidelines. Our meta-analysis aimed to better elucidate its activity, efficacy and safety. Material and methods: A systematic search of Medline, Web of Science and conferences proceedings up to 30 October 2017 was carried out to identify randomized controlled trials (RCTs) investigating platinum-based versus platinum-free neoadjuvant chemotherapy in TNBC patients. Using the fixed and random effects models, pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CI) were calculated for pathological complete response (pCR, defined as ypT0/is pN0), event-free survival (EFS), overall survival (OS) and grade 3 and 4 adverse events (AEs: neutropenia, anemia, thrombocytopenia and neuropathy). Results: Nine RCTs (N=2109) were included. Overall, platinum-based neoadjuvant chemotherapy significantly increased pCR rate from 37.0% to 52.1% (OR 1.96, 95% CI 1.46-2.62, P<0.001). Platinum-based neoadjuvant chemotherapy remained significantly associated with increased pCR rate also after restricting the analysis to the three RCTs (N=611) that used the same standard regimen in both groups of weekly paclitaxel (with or without carboplatin) followed by anthracycline and cyclophosphamide (OR 2.53, 95% CI 1.37-4.66, P=0.003). Conversely, among the 96 BRCA-mutated patients included in two RCTs, the addition of carboplatin was not associated with significantly increased pCR rate (OR 1.17, 95% CI 0.51-2.67, P=0.711). Two RCTs (N=748) reported survival outcomes: no significant difference in EFS (HR 0.72, 95% CI 0.49-1.06, P=0.094) and OS (HR 0.86, 95% CI 0.46-1.63, P=0.651) was observed. A significant higher risk of grade 3 and 4 hematological AEs, with no increased risk of grade 3 and 4 neuropathy was observed with platinum-based neoadjuvant chemotherapy. Conclusion: In TNBC patients, platinum-based neoadjuvant chemotherapy is associated with significantly increased pCR rates at the cost of worse hematological toxicities. Platinum-based neoadjuvant chemotherapy may be considered an option in TNBC patients. PROSPERO registration number: CRD42018080042.

Original languageEnglish
Pages (from-to)1497-1508
Number of pages12
JournalAnnals of Oncology
Volume29
Issue number7
DOIs
Publication statusPublished - Jul 1 2018

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Triple Negative Breast Neoplasms
Platinum
Meta-Analysis
Drug Therapy
Confidence Intervals
Randomized Controlled Trials
Odds Ratio
Carboplatin
Disease-Free Survival
Survival
Anthracyclines
Paclitaxel
Neutropenia
Thrombocytopenia
Cyclophosphamide
Anemia
Guidelines
Safety

Keywords

  • BRCA
  • Neoadjuvant chemotherapy
  • Platinum agents
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer : A systematic review and meta-analysis. / Poggio, F.; Bruzzone, M.; Ceppi, M.; Pondé, N. F.; La Valle, G.; Del Mastro, L.; De Azambuja, E.; Lambertini, Matteo.

In: Annals of Oncology, Vol. 29, No. 7, 01.07.2018, p. 1497-1508.

Research output: Contribution to journalReview article

Poggio, F. ; Bruzzone, M. ; Ceppi, M. ; Pondé, N. F. ; La Valle, G. ; Del Mastro, L. ; De Azambuja, E. ; Lambertini, Matteo. / Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer : A systematic review and meta-analysis. In: Annals of Oncology. 2018 ; Vol. 29, No. 7. pp. 1497-1508.
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title = "Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: A systematic review and meta-analysis",
abstract = "Background: The role of platinum-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients is highly controversial and it is not endorsed by current guidelines. Our meta-analysis aimed to better elucidate its activity, efficacy and safety. Material and methods: A systematic search of Medline, Web of Science and conferences proceedings up to 30 October 2017 was carried out to identify randomized controlled trials (RCTs) investigating platinum-based versus platinum-free neoadjuvant chemotherapy in TNBC patients. Using the fixed and random effects models, pooled odds ratios (ORs) and hazard ratios (HRs) with 95{\%} confidence intervals (CI) were calculated for pathological complete response (pCR, defined as ypT0/is pN0), event-free survival (EFS), overall survival (OS) and grade 3 and 4 adverse events (AEs: neutropenia, anemia, thrombocytopenia and neuropathy). Results: Nine RCTs (N=2109) were included. Overall, platinum-based neoadjuvant chemotherapy significantly increased pCR rate from 37.0{\%} to 52.1{\%} (OR 1.96, 95{\%} CI 1.46-2.62, P<0.001). Platinum-based neoadjuvant chemotherapy remained significantly associated with increased pCR rate also after restricting the analysis to the three RCTs (N=611) that used the same standard regimen in both groups of weekly paclitaxel (with or without carboplatin) followed by anthracycline and cyclophosphamide (OR 2.53, 95{\%} CI 1.37-4.66, P=0.003). Conversely, among the 96 BRCA-mutated patients included in two RCTs, the addition of carboplatin was not associated with significantly increased pCR rate (OR 1.17, 95{\%} CI 0.51-2.67, P=0.711). Two RCTs (N=748) reported survival outcomes: no significant difference in EFS (HR 0.72, 95{\%} CI 0.49-1.06, P=0.094) and OS (HR 0.86, 95{\%} CI 0.46-1.63, P=0.651) was observed. A significant higher risk of grade 3 and 4 hematological AEs, with no increased risk of grade 3 and 4 neuropathy was observed with platinum-based neoadjuvant chemotherapy. Conclusion: In TNBC patients, platinum-based neoadjuvant chemotherapy is associated with significantly increased pCR rates at the cost of worse hematological toxicities. Platinum-based neoadjuvant chemotherapy may be considered an option in TNBC patients. PROSPERO registration number: CRD42018080042.",
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author = "F. Poggio and M. Bruzzone and M. Ceppi and Pond{\'e}, {N. F.} and {La Valle}, G. and {Del Mastro}, L. and {De Azambuja}, E. and Matteo Lambertini",
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TY - JOUR

T1 - Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer

T2 - A systematic review and meta-analysis

AU - Poggio, F.

AU - Bruzzone, M.

AU - Ceppi, M.

AU - Pondé, N. F.

AU - La Valle, G.

AU - Del Mastro, L.

AU - De Azambuja, E.

AU - Lambertini, Matteo

PY - 2018/7/1

Y1 - 2018/7/1

N2 - Background: The role of platinum-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients is highly controversial and it is not endorsed by current guidelines. Our meta-analysis aimed to better elucidate its activity, efficacy and safety. Material and methods: A systematic search of Medline, Web of Science and conferences proceedings up to 30 October 2017 was carried out to identify randomized controlled trials (RCTs) investigating platinum-based versus platinum-free neoadjuvant chemotherapy in TNBC patients. Using the fixed and random effects models, pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CI) were calculated for pathological complete response (pCR, defined as ypT0/is pN0), event-free survival (EFS), overall survival (OS) and grade 3 and 4 adverse events (AEs: neutropenia, anemia, thrombocytopenia and neuropathy). Results: Nine RCTs (N=2109) were included. Overall, platinum-based neoadjuvant chemotherapy significantly increased pCR rate from 37.0% to 52.1% (OR 1.96, 95% CI 1.46-2.62, P<0.001). Platinum-based neoadjuvant chemotherapy remained significantly associated with increased pCR rate also after restricting the analysis to the three RCTs (N=611) that used the same standard regimen in both groups of weekly paclitaxel (with or without carboplatin) followed by anthracycline and cyclophosphamide (OR 2.53, 95% CI 1.37-4.66, P=0.003). Conversely, among the 96 BRCA-mutated patients included in two RCTs, the addition of carboplatin was not associated with significantly increased pCR rate (OR 1.17, 95% CI 0.51-2.67, P=0.711). Two RCTs (N=748) reported survival outcomes: no significant difference in EFS (HR 0.72, 95% CI 0.49-1.06, P=0.094) and OS (HR 0.86, 95% CI 0.46-1.63, P=0.651) was observed. A significant higher risk of grade 3 and 4 hematological AEs, with no increased risk of grade 3 and 4 neuropathy was observed with platinum-based neoadjuvant chemotherapy. Conclusion: In TNBC patients, platinum-based neoadjuvant chemotherapy is associated with significantly increased pCR rates at the cost of worse hematological toxicities. Platinum-based neoadjuvant chemotherapy may be considered an option in TNBC patients. PROSPERO registration number: CRD42018080042.

AB - Background: The role of platinum-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients is highly controversial and it is not endorsed by current guidelines. Our meta-analysis aimed to better elucidate its activity, efficacy and safety. Material and methods: A systematic search of Medline, Web of Science and conferences proceedings up to 30 October 2017 was carried out to identify randomized controlled trials (RCTs) investigating platinum-based versus platinum-free neoadjuvant chemotherapy in TNBC patients. Using the fixed and random effects models, pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CI) were calculated for pathological complete response (pCR, defined as ypT0/is pN0), event-free survival (EFS), overall survival (OS) and grade 3 and 4 adverse events (AEs: neutropenia, anemia, thrombocytopenia and neuropathy). Results: Nine RCTs (N=2109) were included. Overall, platinum-based neoadjuvant chemotherapy significantly increased pCR rate from 37.0% to 52.1% (OR 1.96, 95% CI 1.46-2.62, P<0.001). Platinum-based neoadjuvant chemotherapy remained significantly associated with increased pCR rate also after restricting the analysis to the three RCTs (N=611) that used the same standard regimen in both groups of weekly paclitaxel (with or without carboplatin) followed by anthracycline and cyclophosphamide (OR 2.53, 95% CI 1.37-4.66, P=0.003). Conversely, among the 96 BRCA-mutated patients included in two RCTs, the addition of carboplatin was not associated with significantly increased pCR rate (OR 1.17, 95% CI 0.51-2.67, P=0.711). Two RCTs (N=748) reported survival outcomes: no significant difference in EFS (HR 0.72, 95% CI 0.49-1.06, P=0.094) and OS (HR 0.86, 95% CI 0.46-1.63, P=0.651) was observed. A significant higher risk of grade 3 and 4 hematological AEs, with no increased risk of grade 3 and 4 neuropathy was observed with platinum-based neoadjuvant chemotherapy. Conclusion: In TNBC patients, platinum-based neoadjuvant chemotherapy is associated with significantly increased pCR rates at the cost of worse hematological toxicities. Platinum-based neoadjuvant chemotherapy may be considered an option in TNBC patients. PROSPERO registration number: CRD42018080042.

KW - BRCA

KW - Neoadjuvant chemotherapy

KW - Platinum agents

KW - Triple-negative breast cancer

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U2 - 10.1093/annonc/mdy127

DO - 10.1093/annonc/mdy127

M3 - Review article

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JO - Annals of Oncology

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SN - 0923-7534

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