Association between neoadjuvant paclitaxel dose intensity and outcomes in early triple-negative and HER2-positive...

Reduction of paclitaxel dose intensity (PDI) is frequent during neoadjuvant treatment of high-risk early triple-negative (TN) and human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), due to toxicity. The association between PDI and cancer outcomes is uncertain.

We collected across eight European cancer centers (DigiCore consortium) a cohort of early TN and HER2-positive BC patients who received neoadjuvant anthracyclines and weekly paclitaxel. For each subtype, we assessed whether a threshold of reduced PDI (through dose reduction, treatment delay or early cessation) was associated with reduced pathological complete response (pCR) rate. We then described the association between reduced PDI, invasive BC-free survival (IBCFS), and overall survival.

We included 514 TNBC and 249 HER2-positive BC patients. PDI reductions were required in 82.9% and 63.9% of patients, respectively. The optimal cut-off separating high and low PDI was 69% and 72%, respectively. Low PDI was in TNBC (29.8% of patients), but not in HER2-positive BC (22.1% of patients), significantly associated with a reduced pCR rate, compared with high PDI (37.3% versus 55.1%) (odds ratio 0.48, 95% confidence interval 0.33-0.71, P < 0.001). In TNBC, the estimated IBCFS at 36 months was 77.9% in the PDI-low and 89.2% in the PDI-high group (hazard ratio 2.19, 95% confidence interval 1.29-3.73, P = 0.004).

Reduction of PDI is frequently required during neoadjuvant treatment in early TNBC and HER2-positive BC, and is associated with lower pCR rate and IBCFS in TNBC. Reduction of PDI needs careful consideration, balancing adverse events and potential impact. Confirmation in independent datasets is warranted.