PERJETA APPROVED BY EMA FOR METASTATIC BREAST CANCER 

The European Medicines Agency has approved pertuzumab (Perjeta, Roche/Genentech) for patients with HER2-positive metastatic breast cancer, the company announced today.

Specifically, pertuzumab is approved in combination with trastuzumab (Herceptin, Roche/Genentech) and docetaxel for patients with HER2-positive metastatic or locally recurrent unresectable breast cancer who have not received previous anti-HER2 therapy or chemotherapy for their metastatic disease.

"The combination of [pertuzumab], [trastuzumab], and chemotherapy is the first to significantly extend survival, compared with the previous standard of care — [trastuzumab] and chemotherapy alone," said Hal Barron, MD, chief medical officer and head of global product development at Roche, in a press statement.

In 2012, pertuzumab was approved for the same indication in the United States, where trastuzumab plus pertuzumab reportedly costs about $188,000 for an 18-month course of treatment.

The European approval comes after the phase 3 CLEOPATRA (Clinical Evaluation of Pertuzumab and Trastuzumab) trial showed that survival was a median of 6.1 months longer with the triple-drug combination of pertuzumab, trastuzumab, plus docetaxel than with trastuzumab plus docetaxel alone, with no disease worsening or death.

The CLEOPATRA results were first presented at the San Antonio Breast Cancer Symposium in 2011,as reported at the time by Medscape Medical News, and simultaneously published in the New England Journal of Medicine (2012;366:109-119).

The pertuzumab combination also improved overall survival and objective response rate, compared with trastuzumab plus chemotherapy.

In CLEOPATRA, median overall survival was 37.6 months for trastuzumab plus chemotherapy. At the time of the analysis, median overall survival had not been reached for the pertuzumab combination; more than half of that group continued to survive.

As a single agent, pertuzumab has been described as having only "modest antitumor activity." However, preclinical studies have shown that pertuzumab and trastuzumab have a synergistic effect.

Because pertuzumab and trastuzumab have complementary mechanisms of action and bind at different epitopes, the combination of the 2 agents provides a "more comprehensive blockade of HER2 signaling, and results in greater antitumor activity than either agent alone," the CLEOPATRA investigators wrote in 2011.

The most common (>30%) adverse reactions observed with pertuzumab in combination with trastuzumab plus docetaxel were neutropenia, nausea, fatigue, rash, and peripheral neuropathy. The most common (>2%) grade 3/4 adverse reactions were neutropenia, febrile neutropenia, leukopenia, diarrhea, peripheral neuropathy, anemia, asthenia, and fatigue.

The CLEOPATRA investigators also pointed out that the triple therapy did not result in an increase in left ventricular systolic dysfunction.