Neoadjuvant chemotherapy plus dual HER2 blockade is more effective than endocrine therapy (ET) plus dual HER2 blockade in patients with hormone receptor (HR)-positive, HER2-positive breast cancer, according to research published in JAMA Oncology.
In this phase 2 study, the pathologic complete response (pCR) rate was significantly higher in patients who received paclitaxel plus trastuzumab and pertuzumab than in patients who received ET plus trastuzumab and pertuzumab.
The trial (ClinicalTrials.gov identifier: NCT03272477) included 207 patients with HR-positive, HER2-positive breast cancer. The median age of the cohort was 53 (range, 25-83) years, 58% of patients had cT2 to cT4 tumors, 28% had node-positive disease, 66% had stage II-III disease, and 43% had grade 3 tumors.
The patients were randomly assigned to receive trastuzumab plus pertuzumab with either paclitaxel (n=107) or ET (n=100) for 12 weeks. ET consisted of tamoxifen, anastrozole, letrozole, or exemestane.
The primary endpoint was pCR. The pCR rate was 56.4% in the chemotherapy arm and 23.7% in the ET arm (odds ratio, 0.24; 95% CI, 0.12-0.46; P <.001).
In an exploratory analysis, HER2 expression was an independent predictor of pCR. Among patients with the highest HER2 expression, the pCR rate was 70.0% with chemotherapy and 55.6% with ET. Among patients with the lowest HER2 expression, the pCR rates were 20.0% with chemotherapy and 0.0% with ET.
Patients with a HER2-enriched subtype had higher pCR rates with chemotherapy and ET (60.8% and 34.8%, respectively) than patients with a luminal A/B subtype (40.7% and 3.9%, respectively).
Health-related quality of life remained stable throughout neoadjuvant treatment in the ET arm but decreased in the chemotherapy arm.
There were 23 serious adverse events (AEs) — 10 in the ET arm and 13 in the chemotherapy arm. There were 35 grade 3-4 AEs — 5 in the ET arm and 30 in the chemotherapy arm. The most common grade 3-4 AEs in the chemotherapy arm were diarrhea (4%) and infections (3%).
Based on these results, the researchers concluded that paclitaxel plus trastuzumab and pertuzumab is a “universally applicable, efficacious, and well-tolerated standard regimen” for patients with intermediate- to high-risk, HR-positive, HER2-positive breast cancer.
Disclosures: This research was supported by Roche Pharma AG. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Gluz O, Nitz UA, Christgen M, et al. Efficacy of endocrine therapy plus trastuzumab and pertuzumab vs de-escalated chemotherapy in patients with hormone receptor–positive/ERBB2-positive early breast cancer: The neoadjuvant WSG-TP-II randomized clinical trial. JAMA Oncol. Published online May 11, 2023. doi:10.1001/jamaoncol.2023.0646