PAM50 HER2-E Subtype Predicts pCR Following Lapatinib, Trastuzumab

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Researchers investigated with subpopulations could benefit from dual anti-HER2 therapies without chemotherapy.
Researchers investigated with subpopulations could benefit from dual anti-HER2 therapies without chemotherapy.

SAN ANTONIO – PAM50 HER2-enriched subtype is associated with response following neoadjuvant lapatinib and trastuzumab with or without endocrine therapy in patients with HER2-positive breast cancer, a study presented at the 2016 San Antonio Breast Cancer Symposium (SABCS) has shown.1

Previous studies have demonstrated that 6% to 36% of patients with HER2-positive breast cancer achieve pathologic complete response with neoadjuvant dual HER2 blockade without chemotherapy. It is unclear, however, which subpopulations derive the maximum benefit from dual anti-HER2 therapies without chemotherapy.

To evaluate the ability of the PAM50 HER2-enriched intrinsic subtype to predict pathologic complete response in the breast following 18 weeks of neoadjuvant dual HER2 blockade, researchers designed the multicenter, open-label, phase 2, translational research PAMELA study (ClinicalTrials.gov Identifier: NCT01973660).

For the study, investigators enrolled 151 patients with HER2-positive breast cancer to receive neoadjuvant therapy with lapatinib and trastuzumab for 18 weeks. Of those, 60.2% were postmenopausal, 63.5% had negative axillary lymph nodes, and 66.9% had the PAM50 HER2-enriched subtype. Patients with HR-positive disease also received tamoxifen if premenopausal or letrozole if postmenopausal.

Researchers found that 30.5% of patients overall, 18.2% with HR-positive disease, and 43.2% with HR-negative disease achieved a pathologic complete response. In addition, 40.6% of patients with the HER2-enriched subtype achieved a pathologic complete response compared with 10.0% of those with non-HER2-enriched subtypes (P <.0001).

“We prospectively confirmed that the HER2-enriched subtype is a strong predictor of sensitivity to dual HER2 blockade within HER2-positive breast cancer in the absence of chemotherapy,” said Aleix Prat, MD, Phd, Vall d'Hebron Institute of Oncology, Barcelona, Spain.

Among patients with HR-positive disease, 31.6% of patients with the HER2-enriched subtype had a pathologic complete response, vs 5.3% of those with non-HER2-enriched subtypes (P =.006). Among patients with HR-negative disease, 46.0% and 27.3% of those with and without the HER2-enriched subtype achieved a pathologic complete response, respectively (P =.331).

“PAM50 at baseline and at week 2 provides independent information compared to HR status, which is the only molecular predictor to data consistently found to be associated with pathologic complete response in HER2-positive disease,” noted Dr Prat.

“Studies evaluating the long-term survival outcomes of chemotherapy-free dual HER2 blockade are justified after selecting patients based on variables such as intrinsic subtyping,” concluded Dr Prat. “Further validation of PAM50, PiK3CA mutations, and PTEN loss is ongoing in collaboration with the Translational Breast Cancer Research Consortium group.”

Reference

1. Prat Aparicio A, Cortes Castan J, Pare L, et al. PAM50 intrinsic subtype as a predictor of pathological complete response following neoadjuvant dual HER2 blockade without chemotherapy in HER2-positive breast cancer: first results of the PAMELA clinical trial. Paper presented at: 2016 San Antonio Breast Cancer Symposium; December 6-10, 2016; San Antonio, TX.
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