Adding weekly carboplatin to sequential anthracycline and paclitaxel-based chemotherapy as neoadjuvant treatment for triple negative breast cancer (TNBC) patients: a propensity scorematched study

Background: The addition of carboplatin (Cb) to neoadjuvant anthracycline and taxane -based chemotherapy for TNBC increases pathological complete response (pCR) rate at the cost of worse hematologic toxicity. However, treatment schedules and doses adopted in randomized trials were not always consistent with current clinical practice. We evaluated the role of adding weekly Cb (wCb) to neoadjuvant sequential anthracycline and paclitaxel. Methods: Clinicopathological data of TNBC (ER & PgR<10%) patients treated at three Institutions (Istituto Oncologico Veneto IOV-IRCCS – Padova, Policlinico Gemelli – Roma, AOUI – Modena) were retrieved. Patients should have received sequential treatment with anthracycline- based chemotherapy and weekly paclitaxel (A/wP) with or without wCb. Propensity score was used to control selection bias. Variables considered for matching were: age (continuous), cT (cT1 vs cT2 vs cT3-4), cN (pos vs neg), histologic grade (2 vs 3), BRCA status (mutated vs non informative or unknown). A caliper width of 0.2 was applied for matching. Binary logistic regression was used to test the association of Cb treatment with pCR (ypT0/is ypN0). Cox regression was used for survival analyses. Results: 247 patients were included: 60% treated with A/ wP+wCb, 40% with A/wP. Main characteristics: median age 51 yrs, ductal histology 95%, histologic grade 3 95%, cT1 18%, cT2 66%, cT3-4 16%, cN+ 51%, BRCA mutated 13%. After propensity score matching, pCR rate was significantly higher for A/wP+wCb vs A/wP in logistic regression analysis corrected for matching variables: 47% vs 33% (OR 2.14 95%CI 1.08-4.23, p=0.029). Grade⩾3 neutropenia was more frequent with wCb (35% vs 47%). The achievement of pCR was significantly 10 Tumori Journal 107(2S) associated with improved disease-free survival (HR 0.26, 95%CI 0.11-0.63, p=0.003). No difference in disease-free survival was observed comparing A/wP+wCb vs A/wP: HR 1.50, 95%CI 0.79-2.85, p=0.220. Conclusions: The relative and absolute positive effect on pCR of adding wCb to sequential A/wP in a clinical practice setting is in line with data from randomized trials adopting different treatment schedules. Inclusion of wCb increases the risk of hematologic toxicity. Additional data are needed to clarify the impact on long-term survival. These results support the conditional positive GRADE recommendation for Cb inclusion in neoadjuvant chemotherapy for TNBC provided by the AIOM Guidelines on Breast Cancer.