F Poggio1, M Bruzzone2, M Ceppi2, N F Pondé3, G La Valle4, L Del Mastro5, E de Azambuja3, M Lambertini6. 1. Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium; Department of Medical Oncology, Oncologia Medica 2, School of Medicine, University of Genova, Genova, Italy. 2. Unit of Clinical Epidemiology, School of Medicine, University of Genova, Genova, Italy. 3. Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium. 4. Health Direction, School of Medicine, University of Genova, Genova, Italy. 5. Department of Medical Oncology, U.O. Sviluppo Terapie Innovative, Ospedale Policlinico San Martino IRCCS per l'Oncologia, School of Medicine, University of Genova, Genova, Italy; Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genova, Genova, Italy. 6. Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium; Breast Cancer Translational Research Laboratory, Institute Jules Bordet, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium. Electronic address: matteo.lambertini85@gmail.com.
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.
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.
Authors: S González-Santiago; T Ramón Y Cajal; E Aguirre; J E Alés-Martínez; R Andrés; J Balmaña; B Graña; A Herrero; G Llort; A González-Del-Alba Journal: Clin Transl Oncol Date: 2019-12-30 Impact factor: 3.405
Authors: Larissa A Korde; Mark R Somerfield; Lisa A Carey; Jennie R Crews; Neelima Denduluri; E Shelley Hwang; Seema A Khan; Sibylle Loibl; Elizabeth A Morris; Alejandra Perez; Meredith M Regan; Patricia A Spears; Preeti K Sudheendra; W Fraser Symmans; Rachel L Yung; Brittany E Harvey; Dawn L Hershman Journal: J Clin Oncol Date: 2021-01-28 Impact factor: 44.544