Findings Clarify Picture for HER2-Positive Breast Cancer

Lynne Lederman, PhD
Published: Tuesday, May 01, 2018
Adam M. Brufsky, MD, PhD
Adam M. Brufsky, MD, PhD
Major changes for patients with HER2- positive breast cancer are not on the horizon, but there are a number of new study findings that have amplified knowledge about how best to care for this population.

That was the consensus of a panel of breast cancer oncologists who participated in an OncLive Peer Exchange® discussion of research presented at the San Antonio Breast Cancer Symposium (SABCS), held December 5 to 9, 2017, in Texas. These experts reviewed key abstracts on HER2+ breast cancer and provided perspectives on how studies of systemic therapy in this setting may influence clinical practice. Despite many advancements in the past 2 decades, the HER2-positive subtype presents challenges. Metastatic HER2- positive breast cancer remains incurable and represents an unmet medical need.1

Dual-Targeted Neoadjuvant Therapy: Pertuzumab Plus Trastuzumab With Chemotherapy

Adam M. Brufsky, MD, PhD, session moderator, began the discussion by observing that interesting abstracts at SABCS covered both early and late disease. Neoadjuvant therapy in HER2-positive breast cancer has been a tremendous success, he said, noting research on determining the optimal chemotherapy backbone for using neoadjuvant trastuzumab (Herceptin) plus pertuzumab (Perjeta).

Trastuzumab (H) and pertuzumab (P) is approved as a standard neoadjuvant therapy for stage II to III HER2-positive breast cancer. Francisco J. Esteva, MD, PhD, discussed a singlecenter, retrospective study that evaluated chemotherapy used with neoadjuvant pertuzumab- containing regimens in this setting.2 The study evaluated rates of pathologic complete response (pCR) in 226 patients with stage II to III HER2-positive breast cancer who received neoadjuvant trastuzumab plus pertuzumab (PH) in combination with backbone chemotherapies that included a taxane (T), an anthracycline and cyclophosphamide (A), or carboplatin (C). Combination therapies included paclitaxel, trastuzumab, and pertuzumab (THP) and docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP).

The pCR rates were 65% for THP (n = 48), 50% for TCHP (n = 90, including 5 who received TCHP-A), and 58% for THP-A (n = 88); these differences were not statistically significant. Esteva said it was reassuring that THP did not result in a lower pCR rate than TCHP or THP followed by adjuvant chemotherapy.

“How those patients were selected, though, and why is the question,” he commented. “It’s something to keep in mind—that some patients may do very well with THP, like they did in the NeoSphere trial, which was the FDA registration trial for pertuzumab.” In the phase II NeoSphere trial (NCT00545688), patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer were randomly assigned to neoadjuvant H plus docetaxel (HT), docetaxel plus HP (THP), HP, or P plus docetaxel (PT).3 After surgery, patients received 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) chemotherapy. The study showed that progression- free survival (PFS) rates were highest for the groups receiving THP or HT.

Patients who experienced pCR after any neoadjuvant combination had longer PFS. If patients experience pCR on neoadjuvant therapy, Esteva said, they might not need FEC after surgery. However, because patients received THP, then surgery, and then FEC, the pCR rates without adjuvant chemotherapy are unknown.

Hope S. Rugo, MD, pointed out that in the APHINITY trial (NCT01358877) of pertuzumab added to adjuvant trastuzumab and chemotherapy,4 as well as in the NeoSphere trial, the rates of grade 3 diarrhea are high. Using weekly paclitaxel plus trastuzumab plus pertuzumab is much better tolerated, Rugo said. “The idea is, less is more,” she continued. After induction therapy and response evaluation, additional therapy could be selected for patients based on tumor characteristics and tolerance. Rugo said that she thinks that weekly paclitaxel with THP is a better choice than docetaxel for older patients, and Komal Jhaveri, MD, noted that neutropenia is a serious adverse effect with docetaxel. Brufsky and Lee Schwartzberg, MD, said that they administer growth factors to all their patients with breast cancer because of the risk of neutropenia.

Schwartzberg expressed comfort with using docetaxel in older patients, although weekly paclitaxel is an option for patients with low-risk disease. Esteva administers weekly THP for 12 weeks, followed by dose-dense adjuvant chemotherapy before surgery, noting that some patients might not need it, but it’s difficult to tell. Because of toxicity, he said, he doesn’t like administering docetaxel or carboplatin.

Rugo says that her practice administers paclitaxel first, then 4 doses of pertuzumab, followed by dose-dense adjuvant chemotherapy. “But now, if somebody has a pCR essentially by exam and imaging after their THP, it’s hard to give them adjuvant chemotherapy, especially for older patients,” she added.

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