Nab-Paclitaxel Combo Improves Response vs SOC in HER2+ Breast Cancer

Nab-paclitaxel elicited a pathologic complete response rate of 66.3% compared with 57.6% with docetaxel plus carboplatin, the phase 3 HELEN-006 trial found.

Neoadjuvant nab-paclitaxel (Abraxane) in combination with trastuzumab (Herceptin) and pertuzumab (Perjeta) elicited outcomes that suggest an advantage in the treatment of patients with HER2-positive early breast cancer when compared with standard-of-care, docetaxel (Taxotere) plus carboplatin, with trastuzumab and pertuzumab, according to the phase 3 HELEN-006 trial (NCT04547907) published in Lancet Oncology.

Patients were assigned to either the experimental arm where they received nab-paclitaxel, trastuzumab, and pertuzumab, or to the comparator arm where they received docetaxel, carboplatin, trastuzumab, and pertuzumab.

At a median follow-up of 26 months (IQR, 19-32), of the 669 patients included in the final analysis, 62% had a pathologic complete response (pCR). Further, 66.3% (95% CI, 61.2%-71.4%) of patients in the nab-paclitaxel group experienced a pCR, compared with 57.6% (95% CI, 52.3%-62.9%) of patients in the docetaxel plus carboplatin group (combined odds ratio, 1.54; 95% CI, 1.10-2.14).

“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,” lead study author Chen Xiu-Chun, MM, and fellow study authors wrote. “In addition to having fewer adverse effects [AEs], the patients receiving the 18-week nab-paclitaxel regimen had higher pCR rates than the control group, showing that this treatment regimen can reduce toxicity without compromising efficacy.”

The study’s primary end point 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 end points were event-free survival, invasive-disease-free survival, safety, and tolerability.

A total of 689 patients were randomly assigned, in a 1:1 ratio, using an interactive response system and permuted blocks at a size of 4 and stratified based on tumor stage (T1-2 vs T3-4), nodal status (N0 vs N-positive confirmed by biopsy), and hormone receptor status (positive vs negative), to receive either nab-paclitaxel or docetaxel with carboplatin, then both groups received trastuzumab and pertuzumab.

The 322 patients in the nab-paclitaxel group were to receive 125 mg/m² of intravenous nab-paclitaxel on days 1, 8, and 15 for each of six 3-week-long cycles. The 337 patients in the docetaxel plus carboplatin group were to receive 75 mg/m² of intravenous docetaxel on day 1 and intravenous carboplatin at a dose based on area under the concentration-time curve of 6 mg/mL per minute on day 1 of each cycle. Both groups received the same trastuzumab and pertuzumab doses: 8 mg/kg of intravenous trastuzumab and a maintenance dose of 6 mg/kg on day 1, and 840 mg of intravenous pertuzumab and a maintenance dose of 420 mg on day 1.

The trial enrolled patients between 18-70 years old 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 excluded if they had bilateral breast cancer, history of other malignancies except for adequately treated skin cancer, previous systemic therapy for the treatment/prevention of breast cancer, and contraindications to the study drugs.

Regarding AEs, 34% of the 669 patients analyzed experienced at least 1 grade 3/4 AE; 30% in the nab-paclitaxel group and 38% in the docetaxel plus carboplatin group. The most common AEs of grade 3/4 were nausea (7% of the nab-paclitaxel group vs 23% of the docetaxel group), diarrhea (8% vs 16%, respectively), and neuropathy (13% vs 2%, respectively). For anemia, leukopenia, neutrophilia, thrombocytopenia, nausea, vomiting, and diarrhea, there were “substantially” fewer grade 3 or 4 AEs in the nab-paclitaxel group compared with the docetaxel group. Nab-paclitaxel had higher rates of grade 3 or 4 neuropathy, increased alanine aminotransferase, and increased aspartate aminotransferase.

In the nab-paclitaxel group, 17% of patients required dose reductions vs 26% of patients in the docetaxel group. Also, 9% of patients in the nab-paclitaxel group and 7% of patients in the docetaxel group discontinued treatment. There were no treatment-related deaths.

Reference

Chen XC, Jiao DC, Qiao JH, et al. De-escalated neoadjuvant weekly nab-paclitaxel with trastuzumab and pertuzumab versus docetaxel, carboplatin, trastuzumab, and pertuzumab in patients with HER2-positive early breast cancer (HELEN-006): a multicentre, randomised, phase 3 trial. Lancet Oncol. Published online November 26, 2024. doi:10.1016/S1470-2045(24)00581-3