Key Studies Help Chart Course in HER2-Positive Breast Cancer

Published: Sunday, Feb 28, 2016
Sara A. Hurvitz, MD

Sara A. Hurvitz, MD

Among the bright spots in the treatment of patients with breast cancer are the successes achieved in the management of HER2-positive disease. And, therapeutic options are continuing to expand, owing to the advent of novel anti-HER2–targeted agents and multitargeted HER2 receptor blockade.

These were among the key take-home messages that breast cancer experts conveyed during a recent OncLive Peer Exchange® roundtable entitled “Update on Advanced Breast Cancer Treatment.” The prognosis for newly diagnosed first-line disease “is very good in terms of median survivals” which are “now approaching 5 years,” said Sara A. Hurvitz, MD. First- and second-line strategies for treatment of patients with HER2-positive, metastatic breast cancer is straightforward, and the therapies are “really well tolerated,” Hurvitz noted. “It’s just not the depressing, horrible story that it was a decade or more ago,” she said.

Pertuzumab Plus Trastuzumab

The recent study that decisively changed the therapeutic landscape is the CLEOPATRA trial,1 which introduced the concept of dual HER2 targeting. CLEOPATRA randomized patients with metastatic breast cancer who had not received previous chemotherapy or anti-HER2 therapy for metastatic disease to trastuzumab and docetaxel with either pertuzumab or placebo.

Patients received 4 to 6 cycles of chemotherapy, and then were allowed to come off of the chemo and continue only the HER2-targeted agent or agents. In CLEOPATRA, progression-free survival (PFS) was 6 months longer among patients who received pertuzumab/trastuzumab/ docetaxel together as compared with those who only received trastuzumab/docetaxel. Patients who received the pertuzumab-containing regimen achieved a median overall survival (OS) of 56.5 months compared with 40.8 months for the placebo group (HR, 0.68; P <.001).

The therapy was well tolerated, and the addition of pertuzumab to trastuzumab did not appear to increase cardiac toxicity, said Hurvitz. However, clinicians should “forewarn patients that, especially during the time they are receiving chemotherapy,” the treatment “increases rates of diarrhea and skin toxicity,” she recommended. Hurvitz expressed dismay that “a lot of community oncologists drop off the pertuzumab somewhere around 8 or 9 cycles.” Additional panel participants responded to this observation by saying they had observed the same pattern. During the trial, the pertuzumab/trastuzumab combination was administered until disease progression or the onset of unmanageable toxicities. “The message I try and get out to referring oncologists is to follow the way the study was done,” Hurvitz said.

Hope S. Rugo, MD

Hope S. Rugo, MD

However, she explained, CLEOPATRA did not initiate endocrine therapy with the dual HER2-targeted therapies for estrogen receptor (ER)–positive disease, although “in my practice I do because I think dual blockade is probably beneficial,” athough she does not have data supporting that approach.

The FDA has approved pertuzumab for use in combination with trastuzumab and docetaxel for treatment of patients with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease, and in combination with trastuzumab and docetaxel as neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer (either >2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer.2 As to whether either docetaxel or paclitaxel is superior in such a regimen incorporating trastuzumab and pertuzumab, Hurvitz noted that recent data indicate “that paclitaxel is probably just as good,” and so choosing between them should be based on the characteristics of the patient, the timing, and known side effects of the therapy.

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