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Acquired HER2 Mutations Cause Endocrine Resistance in ER+ Breast Cancer

Jason M. Broderick @jasoncology
Published: Thursday, Mar 15, 2018

Elaine R. Mardis, PhD
Elaine R. Mardis, PhD
Acquired HER2 mutations cause endocrine resistance in some patients with ER+/HER2-negative breast cancer, according to findings reported during a media preview for the 2018 AACR Annual Meeting.

= .0064). The median PFS was 8.3 months for the lapatinib/AI arm.

The phase II PERTAIN trial enrolled 258 postmenopausal women with HER2-positive, HR-positive locally advanced or metastatic breast cancer. Patients were randomized to receive pertuzumab (Perjeta) with trastuzumab (n= 129) or trastuzumab alone (n = 129) in combination with an AI. Based on investigator's discretion, induction chemotherapy could be given for 18 to 24 weeks prior to starting endocrine therapy.

The median PFS was 18.89 months with the pertuzumab triplet compared with 15.80 months for trastuzumab and an AI alone (HR, 0.65; P = .0070). In patients with measurable disease, the ORR with the pertuzumab combination was 63.3% compared with 55.7% for trastuzumab and an AI alone.

A study recently published in The Lancet Oncology, suggests that the next step in this area might be not only dual targeting, but also trying to enhance the impact of endocrine therapy by adding a CDK4/6 inhibitor.

The phase II NA-PHER2 study accrued 36 patients with previously untreated, histologically confirmed, unilateral, invasive, ER-positive/HER2-positive cancer. Thirty patients were included in this first endpoint analysis.

The study showed that the neoadjuvant combination of palbociclib (Ibrance), pertuzumab, fulvestrant, and trastuzumab had a high clinical response. Twenty-nine (97%) of 30 patients had a response, including 15 complete responses and 14 partial responses.
Nayar U, Cohen O, Kapstad C, et al. Acquired HER2 mutations in ER+ metastatic breast cancer confer resistance to ER-directed therapies. 2018 AACR Annual Meeting; April 14-18, 2018; Chicago, IL.


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