A phase 3 trial has revealed that a neoadjuvant regimen of nab-paclitaxel (Abraxane) combined with trastuzumab (Herceptin) and pertuzumab (Perjeta) demonstrates a statistically significant improvement in pathologic complete response (pCR) rates compared to the standard-of-care docetaxel (Taxotere) plus carboplatin when also combined with trastuzumab and pertuzumab in patients with HER2-positive early breast cancer. The HELEN-006 trial, published in Lancet Oncology, suggests a potential shift in treatment strategy for this patient population.
Superior Pathologic Complete Response with Nab-Paclitaxel
The multicenter, randomized HELEN-006 trial (NCT04547907) compared the efficacy of nab-paclitaxel versus docetaxel plus carboplatin, both in combination with trastuzumab and pertuzumab. The primary endpoint was pCR rate, defined as the absence of residual invasive carcinoma in all sampled ipsilateral axillary lymph nodes and the resected breast specimen. Key secondary endpoints included event-free survival, invasive-disease-free survival, safety, and tolerability.
At a median follow-up of 26 months, the study, which included 669 patients, demonstrated a pCR rate of 66.3% (95% CI, 61.2%-71.4%) in the nab-paclitaxel group compared to 57.6% (95% CI, 52.3%-62.9%) in the docetaxel plus carboplatin group, resulting in a combined odds ratio of 1.54 (95% CI, 1.10-2.14).
Reduced Adverse Events
In addition to the improved pCR rates, the nab-paclitaxel regimen was associated with a more favorable safety profile. Grade 3/4 adverse events (AEs) were less frequent in the nab-paclitaxel group (30%) compared to the docetaxel plus carboplatin group (38%). Specifically, the nab-paclitaxel group experienced substantially fewer grade 3 or 4 AEs such as nausea (7% vs 23%), diarrhea (8% vs 16%), anemia, leukopenia, neutrophilia, thrombocytopenia and vomiting. However, the nab-paclitaxel group had higher rates of grade 3 or 4 neuropathy, increased alanine aminotransferase, and increased aspartate aminotransferase.
Dose reductions were required in 17% of patients in the nab-paclitaxel group versus 26% in the docetaxel group. Treatment discontinuation rates were similar between the two groups (9% vs 7%, respectively), and no treatment-related deaths were reported.
Study Design and Patient Population
The trial enrolled 689 patients aged 18-70 years with previously untreated, histologically confirmed clinical stage II-III invasive HER2-positive breast cancer who were eligible for surgery and had an ECOG performance status of 0 or 1. Patients were randomized in a 1:1 ratio to receive either nab-paclitaxel (125 mg/m2 intravenously on days 1, 8, and 15 of each 3-week cycle for six cycles) or docetaxel (75 mg/m2 intravenously on day 1 of each cycle) plus carboplatin (AUC = 6 mg/mL per minute on day 1 of each cycle). Both groups received trastuzumab (8 mg/kg intravenously, followed by 6 mg/kg maintenance) and pertuzumab (840 mg intravenously, followed by 420 mg maintenance) on day 1 of each cycle.
Clinical Implications
"To our knowledge, the HELEN-006 study is the first prospective, randomized, phase 3 trial comparing a weekly nab-paclitaxel regimen with dual HER2 blockade to the standard docetaxel plus carboplatin regimen with dual HER2 blockade in patients with HER2-positive early-stage breast cancer," noted lead study author Chen Xiu-Chun, MM, and colleagues. The study authors concluded that the 18-week nab-paclitaxel regimen can reduce toxicity without compromising efficacy, potentially establishing it as a preferred neoadjuvant option in this setting.
