Abstract 141P
Background
Neoadjuvant treatment (NAT) with anthracyclines and paclitaxel is the backbone for high-risk early triple-negative (TN) and HER2-positive (HER2+) breast cancer (BC). Due to toxicity, reduction of paclitaxel dose intensity (PDI) during NAT is required in 30-40% of patients. The association between reduced PDI and BC outcomes is unknown.
Methods
We collected across eight European comprehensive cancer centers (DigiCore consortium) a cohort of early TN and HER2+ BC patients with a NAT plan of four cycles of anthracyclines and 12 cycles of paclitaxel. We compared patients that had a high and low PDI (due to dose reduction, treatment delay and/or early cessation). Primary endpoints were pathological complete response (pCR) and invasive BC free survival (IBCFS). Secondary endpoints were overall survival (OS) and analyses by BC subtype. We sought the optimal cut-off value of PDI (high vs low) using the classification and regression tree algorithm.
Results
Of the 763 patients included, 514 (67%) were TN and 249 (33%) HER2+ BC. Of these, 67% had a reduction in PDI. Mean PDI was 79 ± 20%. The cut-off to separate high and low PDI was found at 73%. The percentage of patients achieving pCR was 38.3% in the PDI-low and 55.5% in the PDI-high group (odd ratio 0.55 ; 95% confidence interval [CI] 0.36 to 0.68 ; p<0.001). With a median follow-up of 28 months, the estimated IBCFS at 36 months was 82.1% in the PDI-low and 90.4% in the PDI-high group (hazard ratio [HR] 2.00 ; 95% CI 1.23 to 3.23 ; p=0.005). The estimated OS at 36 months was 88.8% in the PDI-low and 95.6% in the PDI-high group (HR 2.19 ; 95% CI 1.14 to 4.21 ; p=0.019). PDI remained significant to predict pCR/IBCFS in multivariate analyses. In subgroups, pCR rate and estimated IBCFS at 36 months were significantly associated with PDI in TNBC, but not in the smaller group of HER2+ BC.
Conclusions
Reduction of PDI is frequently required during NAT of early TN and HER2+ BC, with a significant and clinically meaningful negative impact on pCR rate, IBCFS and OS. Reduction of PDI should not be considered without a relevant medical reason, especially in TNBC. Strategies to minimise low PDI should be investigated.
Legal entity responsible for the study
Masaryk Memorial Cancer Institute.
Funding
DIGICORE.
Disclosure
C. Van Marcke: Financial Interests, Institutional, Advisory Board: eli Lilly, Novartis, AstraZeneca; Financial Interests, Institutional, Invited Speaker: Merck; Non-Financial Interests, Member of Board of Directors: BSMO. K. Pogoda: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Gilead, Novartis, Eli Lilly, Pfizer; Financial Interests, Personal, Advisory Board: Sandoz, AstraZeneca; Financial Interests, Personal, Full or part-time Employment, Assistant Professor: Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland; Financial Interests, Personal and Institutional, Other, SI: Novartis, Roche, Eli Lilly, AstraZeneca; Non-Financial Interests, Other, Breast Cancer Group - Steering Committee Member, Quality of Life Group: EORTC; Non-Financial Interests, Member: Polish Society of Clinical Oncology, Polish Society of Oncology. H. Fenton, M. Borges: Financial Interests, Personal, Full or part-time Employment: IQVIA. All other authors have declared no conflicts of interest.