The value of adding carboplatin (Cb) to neoadjuvant chemotherapy for TNBC is debated. Current evidence supports the association between Cb use and increased pathological complete response (pCR) rate. However, treatment schedules and doses adopted in randomized trials were not always consistent with those used in clinical practice.
Clinicopathological data of TNBC (ER & PgR<10%) patients treated at our Institution with neoadjuvant anthracycline and taxane (AT) with or without Cb were collected. Propensity score was used to control selection bias. Variables considered for matching were: age, Ki67, cT, cN, histologic grade, histotype, BRCA status. Tumor infiltrating lymphocytes (TILs) were not used as matching variable since data were lacking for 39% of cases. The distribution of TILs in the two matched groups was similar (p = 0.669). Binary logistic regression was used to test the association of Cb treatment with pCR (ypT0/is ypN0). Cox regression was used for survival analyses.
166 patients were included: 61% treated with AT, 39% with AT+Cb (all patients in this group received Cb AUC2 weekly administered concomitantly to the taxane segment). Main characteristics: median age 50 yrs, ductal histology 93%, grade 3 90%, cT > 2cm 86%, cN + 57%, median TILs 10%, median Ki67 60%, BRCA mutated 10%. After propensity score matching, pCR rate was significantly higher for AT+Cb vs AT: 52% vs 31% (OR 2.39 95%CI 1.04-5.50, p = 0.040). In multivariable analysis, treatment with AT+Cb maintained an independent association with pCR: OR 2.51 95%CI 1.03-6.11, P = 0.043. The achievement of pCR was significantly associated with improved disease-free survival (HR 0.16, 95%CI 0.06-0.45). No difference in DFS was observed comparing AT+Cb vs AT: HR 0.99, 95%CI 0.44-2.25.
We confirmed in a clinical practice setting the association of Cb-containing neoadjuvant chemotherapy with higher pCR rates. Additional data are needed to clarify the impact on long-term survival. These data support the conditional positive recommendation for Cb inclusion in neoadjuvant chemotherapy for TNBC provided by the Italian Association of Medical Oncology Guidelines on Breast Cancer.
Clinical trial identification
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M.V. Dieci: Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Celgene; Advisory / Consultancy: Genomic Health.
V. Guarneri: Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Speaker Bureau / Expert testimony: Eli Lilly; Speaker Bureau / Expert testimony: Novartis; Research grant / Funding (institution): Roche. All other authors have declared no conflicts of interest.