Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis

• Published in: Annals of oncology Vol. 29; no. 7; pp. 1497 - 1508
• Main Authors: Poggio, F., Bruzzone, M., Ceppi, M., Pondé, N.F., La Valle, G., Del Mastro, L., de Azambuja, E., Lambertini, M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2018; Oxford University Press
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; BRCA; Chemotherapy, Adjuvant; Female; Humans; neoadjuvant chemotherapy; Neoadjuvant Therapy; Organoplatinum Compounds - therapeutic use; platinum agents; Prognosis; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - pathology; triple-negative breast cancer; neoadjuvant chemotherapy; BRCA; triple-negative breast cancer; platinum agents
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdy127

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. 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). 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. 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. CRD42018080042.