Abstract
Background
Platinum-based chemotherapy is widely used in patients with advanced triple-negative
breast cancer (TNBC). However, the most effective platinum-based combination in the
first-line treatment setting remains unclear.
Materials and Methods
We evaluated the efficacy of first-line carboplatin-paclitaxel (CP) or carboplatin-gemcitabine
(CG) combinations in advanced TNBC patients treated between April 2007 and April 2021.
CP and CG were compared in terms of progression-free survival (PFS), overall survival
(OS), and incidence of adverse events (AEs). Multivariable Cox Models were used to
adjust the efficacy of CP versus CG for clinically relevant covariates.
Results
Of 88 consecutive advanced TNBC patients receiving first-line carboplatin-based doublets,
56 (63.6%) received CP and 32 (36.4%) CG. After adjusting for clinically relevant
variables, patients receiving CG had significantly better PFS when compared to CP-treated
patients (HR: 0.49 (95% CI, 0.27-0.87), P value 0.014). Of note, CG was associated with better PFS only among patients previously
treated with taxanes in the (neo)adjuvant setting (HR: 0.39; 95% CI, 0.21-0.75), but
not in patients not exposed to taxanes (HR: 1.20; 95% CI, 0.37-3.88). CG was also
independently associated with better OS when compared to CP (HR: 0.31 (95% CI: 0.15-0.64),
P value 0.002). Overall, grade 3-4 AEs were more common in patients treated with CG
than in patients treated with CP (68.8% vs. 21.4%, P value .009).
Conclusion
CG and CP are effective and well tolerated first-line platinum doublets in advanced
TNBC patients. CG could be more effective than CP in patients previous exposed to
taxanes despite worse toxicity profile.
Keywords
Abbreviations:
AEs (Adverse Events), AUC (Area Under the Curve), BC (Breast Cancer), BMI (Body Mass Index), CG (Carboplatin plus Gemcitabine), CI (Confidence Interval), CP (Carboplatin plus Paclitaxel), CR (Complete Response), DCR (Disease Control Rate), DFI (Disease-Free Interval), DOR (Duration Of Response), ECOG (Eastern Cooperative Oncology Group), ER (Estrogen Receptor), HER2 (Human Epidermal Growth Factor Receptor 2), HR (Hazard Ratio), i.v. (Intravenous), IHC (ImmunoHistoChemistry), ISH (In Situ Hybridization), ORR (Overall Response Rate), OS (Overall Survival), PARPi (Polyadenosine Diphosphate-Ribose Polymerase Inhibitors), PD-L1 (Programmed Death-Ligand 1), PFS (Progression Free Survival), PgR (Progesterone Receptor), PR (Partial Response), PS (Performance Status), SD (Stable Disease), TNBC (Triple Negative Breast Cancer)To read this article in full you will need to make a payment
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References
- Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin. 2021; 71: 209-249
- Clinical and biologic features of triple-negative breast cancers in a large cohort of patients with long-term follow-up.Breast Cancer Res Treat. 2012; 136: 795-804
- Incorporation of clinical and biological factors improves prognostication and reflects contemporary clinical practice.NPJ Breast Cancer. 2020; 6: 11
- Triple-negative breast cancer: clinical features and patterns of recurrence.Clin Cancer Res. 2007; 13 (Pt 1): 4429-4434
- Survival with metastatic breast cancer based on initial presentation, de novo versus relapsed.Breast Cancer Res Treat. 2017; 161: 549-556
- IMpassion130 trial investigators. atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer.N Engl J Med. 2018; 379: 2108-2121
- nab-Paclitaxel plus carboplatin or gemcitabine versus gemcitabine plus carboplatin as first-line treatment of patients with triple-negative metastatic breast cancer: results from the tnAcity trial.Ann Oncol. 2018; 29: 1763-1770
- Time trends of overall survival among metastatic breast cancer patients in the real-life ESME cohort.Eur J Cancer. 2018; 96: 17-24
- Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies.J Clin Invest. 2011; 121: 2750-2767
- Biological subtypes of breast cancer: Prognostic and therapeutic implications.World J Clin Oncol. 2014; 5: 412-424
- Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation.N Engl J Med. 2017; 377: 523-533
- Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation.N Engl J Med. 2018; 379: 753-763
- Chemotherapy of metastatic triple negative breast cancer: Experience of using platinum-based chemotherapy.Oncotarget. 2015; 6: 43135-43143
- Mechanism of the formation of DNA-protein cross-links by antitumor cisplatin.Nucleic Acids Res. 2007; 35: 1812-1821
- DNA interstrand crosslink repair and cancer.Nat Rev Cancer. 2011; 11: 467-480
- Results of a phase II open-label, non-randomized trial of cisplatin chemotherapy in patients with BRCA1-positive metastatic breast cancer.Breast Cancer Res. 2012; 14: R110
- Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial.Nat Med. 2018; 24: 628-637
- Single-agent gemcitabine vs. carboplatin-gemcitabine in advanced breast cancer: a retrospective comparison of efficacy and safety profiles.Clin Breast Cancer. 2019; 19 (e18): e306
- Antitumor activity and safety profile of weekly carboplatin plus paclitaxel in metastatic breast cancer: a ten-year, monocentric, retrospective study.Breast Cancer Res Treat. 2017; 165: 365-373
- Weekly paclitaxel and carboplatin plus bevacizumab as first-line treatment of metastatic triple-negative breast cancer. a multicenter phase ii trial by the hellenic oncology research group.Clin Breast Cancer. 2018; 18: 88-94
- Nab-paclitaxel/bevacizumab/carboplatin chemotherapy in first-line triple negative metastatic breast cancer.Clin Breast Cancer. 2013; 13: 416-420
- Phase II studies of gemcitabine and cisplatin in heavily and minimally pretreated metastatic breast cancer.J Clin Oncol. 2009; 27: 2163-2169
- Biweekly gemcitabine-paclitaxel, gemcitabine-carboplatin, or gemcitabine-cisplatin as first-line treatment in metastatic breast cancer after anthracycline failure: a phase II randomized selection trial.Breast Cancer. 2011; 18: 203-212
- Cisplatin plus gemcitabine versus paclitaxel plus gemcitabine as first-line therapy for metastatic triple-negative breast cancer (CBCSG006): a randomised, open-label, multicentre, phase 3 trial.Lancet Oncol. 2015; 16: 436-446
- Vinorelbine and cisplatin in metastatic breast cancer patients previously treated with anthracyclines.Ann Oncol. 2000; 11: 1155-1160
- Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer.J Clin Oncol. 2014; 32: 3840-3847
- Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial.Lancet. 2020; 396: 1817-1828
- Missing data imputation: focusing on single imputation.Ann Transl Med. 2016; 4: 9
- Adjusting survival curves for confounders: a review and a new method.Am J Epidemiol. 1996; 143: 1059-1068
Therneau TM, Crowson CS, Atkinson EJ. Adjusted survival curves. 2015. https://cran.r-project.org/web/packages/survival/vignettes/adjcurve.pdf.
- Resampling Procedures to Compare Two Survival Distributions in the Presence of Right-Censored Data.Biometrics. 1996; 52: 1204-1213
- Platinum-containing regimens for triple-negative metastatic breast cancer.Cochrane Database Syst Rev. 2020; 10CD013750
- Triple negative breast cancer and platinum-based systemic treatment: a meta-analysis and systematic review.BMC Cancer. 2019; 19: 1065
- Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis.Ann Oncol. 2018; 29: 1497-1508
- Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial.Lancet Oncol. 2018; 19: 497-509
- The neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios predict efficacy of platinum-based chemotherapy in patients with metastatic triple negative breast cancer.Sci Rep. 2018; 8: 8703
- Gemcitabine has significant immunomodulatory activity in murine tumor models independent of its cytotoxic effects.Cancer Biol Ther. 2007; 6: 880-885
- Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): a randomised, double-blind, placebo-controlled, phase 3 trial.Lancet Oncol. 2020; 21: 1269-1282
- Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer.N Engl J Med. 2022; 387: 217-226
- A randomized phase 3 trial of Gemcitabine or Nab-paclitaxel combined with cisPlatin as first-line treatment in patients with metastatic triple-negative breast cancer.Nat Commun. 2022; 13: 4025
- Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer.N Engl J Med. 2018; 379: 2108-2121
- Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer.N Engl J Med. 2021; 384: 1529-1541
- Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer.N Engl J Med. 2022; 387: 9-20
Article info
Publication history
Published online: December 16, 2022
Accepted:
December 14,
2022
Received in revised form:
November 19,
2022
Received:
July 22,
2022
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
