Abstract P1-15-19: Carboplatin-addition in neoadjuvant treatment of women with triple negative breast cancer (TNBC): Prognostic value in real-world patients
Authors: Coelho S , Abreu MH , Sales C , Lopes AR , Sousa MF , Couto R , Pousa I , Ferreira A , Ferreira M , Vieira C , Leal C , Castro F , Sousa S , Pereira D 
Published: May 2019

Background

The addition of carboplatin to an anthracycline/taxane-based chemotherapy(CT) in neoadjuvant setting has been suggested to improve pathological complete response(pCR) in TNBC. However, the impact of pCR in prognosis is unknown. We aim to study the value and feasibility of the addition of carboplatin in neoadjuvant setting.

Methods

Demographic and clinical data of TNBC patients treated with neoadjuvant CT in a comprehensive cancer center between 2010-2018 were retrospectively collected. Two cohorts were defined: one treated with Carboplatin/Paclitaxel followed by dose-dense Doxorrubicin/Cyclophosphamide(CP-AC) and other with AC followed by Docetaxel(AC-D). Median follow-up time was 3.1 and 6.9 years, respectively. pCR was defined as absence of residual invasive tumor in breast/axilla. Survival analysis using Kaplan-Meier method and Cox proportional-hazards model were applied. Statistical significance was set at p&lt;0.05.

Results

One-hundred and sixty patients were enrolled: 78 CP-AC and 38 AC-D. Groups were balanced regarding patients and tumor characteristics with exception of pre-menopausal status, more frequent in CP-AC(68% vs 47%;p=.04). Age at diagnosis was 47(28-76)years, the majority had ECOG 0(92%) ductal carcinomas(82%), clinicalT2/3 stages(76%), grade 3(81%) with lymph node involvement(N+)(57%). 14% had Inflammatory breast cancer(IBC)(CP-AC 14%;AC-D 13%; p=.9).

Neutropenia was the most prevalent adverse event(G3/4: CP-AC 61%;AC-D 16%;p=.02), 12% and 16% of febrile neutropenia(p=.8). G3/4 thrombocytopenia occurred only in CP-AC(6%). Hypersensitivity reactions were more prevalent in CP-AC(19% vs 2.7%;p=.02), majority to paclitaxel, all G1/2. Hospital admission occurred in 12%(CP-AC 13%;AC-D 9%; p=.8). There were no treatment-related deaths. Treatment schedule was complete in 89%(CP-AC 87%;AC-D 92%;p=.5), with 20% dose reductions(CP-AC 25%;AC-D 11%;p=0.9).

pCR was achieved in 42%(CP-AC 50%;AC-D 28%;p=.03). 1- and 3-year disease-free survival(DFS) was 94%/85% for CP-AC and 72%/58% for AC-D(p=.3). Risk of recurrence was higher in IBC(HR 25.1;CI95% 7.7-81.3;p&lt;.0001), N+ disease(HR 3.6;CI95% 1.2-10.5;p=.02) and non-pCR(HR 10.9;CI95% 2.3-52.3,p=.003). N+ disease was associated with higher recurrence only in AC-D(HR 11.7;CI95% 1.3-104;p=.03).

Cancer-related deaths were 20%(CP-AC 10%;AC-D 40%;p=.001). 1- and 2-year overall survival (OS) was 99%/95% for CP-AC and 70%/61% for AC-D(p=.06). N+ disease was associated with higher risk of death in AC-D(HR 6.3;CI95% 1.1-24.6;p=.04). Risk of death was independently associated with IBC(HR 4.1;CI95% 2.1-18.7; p=.001) but not with N+ disease(HR 2.7;CI95% 0.8-9.5;p=.13) or pCR(HR 4.1;CI95% 0.9-19.7;p=.08) although pCR was statistically significant in univariate analysis (1- and 2-year OS 97% vs 92% and 94% vs 86% for pCR and non-PCR;p=.003).

Conclusions

Carboplatin addition clearly increased pCR with a trend to DFS and OS benefit. This regimen was associated with more, nevertheless manageable, adverse events with most of the patients able to tolerate and complete the full-dose regimen. Though we did not find a subgroup of patients that benefit with carboplatin regimen, we should consider avoiding AC-D at least in N+ disease.

Citation Format: Coelho S, Abreu MH, Sales C, Lopes AR, Sousa MF, Couto R, Pousa I, Ferreira A, Ferreira M, Vieira C, Leal C, Castro F, Sousa S, Pereira D. Carboplatin-addition in neoadjuvant treatment of women with triple negative breast cancer (TNBC): Prognostic value in real-world patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-19.