EU approves Perjeta for use w herceptin, taxane neoadjuvantly for early stage her2+bc

[Lani]

first EU approval based on pCR rather than PFS, OS


International Approvals > Medscape Medical News
EU Recommends Approval of Neoadjuvant Pertuzumab Regimen
Roxanne Nelson

June 26, 2015


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Breast Cancer and HER2

The EU Committee for Medicinal Products for Human Use (CHMP) has recommended that the European Commission approve pertuzumab (Perjeta, Genentech/Roche) for use in combination with other agents before surgery in women with HER2-positive early-stage breast cancer.

Specifically, the recommendation is for pertuzumab to be used in conjunction with trastuzumab (Herceptin, Genentech/Roche) and chemotherapy in the neoadjuvant setting for women with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer at high risk for recurrence.

"Breast cancer treatment has the greatest impact in the early stage, where it can potentially prevent the disease from returning and spreading," commented Sandra Horning, MD, Roche's chief medical officer and head of global product development, in a statement. "Consequently, there is a need to bring promising treatments to patients with early breast cancer."

The recommendation was primarily based on results of the phase 2 NeoSphere study, which suggested that patients who received pertuzumab in combination with trastuzumab and docetaxel chemotherapy prior to surgery were 31% less likely to experience disease worsening, recurrence, or death (hazard ratio [HR] for progression-free survival (PFS), 0.69; 95% confidence interval [CI], 0.34 - 1.40) compared with those who received trastuzumab and chemotherapy.

Patients who received the pertuzumab regimen were 40% less likely to experience disease recurrence or death (disease-free survival [DFS] HR, 0.60; 95% CI, 0.28 - 1.27).

In addition, patients who achieved pathologic complete response were more likely across all arms of the study to be alive and disease-free at 3 years (PFS HR, 0.54; 95% CI, 0.29 - 1.00; DFS HR, 0.68; 95% CI, 0.36 - 1.26). Nearly 40% of patients receiving the regimen containing pertuzumab achieved pathologic complete response compared with 21.5% of the patients in the other treatment arm.

This is the first CHMP recommendation in the neoadjuvant setting that is based on pathologic complete response.

According to the manufacturer, the CHMP opinion was also based on the total evidence to date, including the biological rationale for combining these agents, the established safety profile, and the efficacy results in the advanced breast cancer setting.

The submission was also based on data from the neoadjuvant TRYPHAENA study, as well as long-term safety results from the CLEOPATRA trial in women with previously untreated HER2-positive advanced breast cancer. Data from the ongoing phase 3 APHINITY study in the adjuvant setting will provide additional insights into the broader role of this agent. Results are expected in 2016.

In 2013, the US Food and Drug Administration (FDA) granted accelerated approval for pertuzumab to be used in combination with other agents prior to surgery. It was initially approved by the FDA in 2012 for patients with metastatic HER2-positive breast cancer, and pertuzumab is the first drug approved by the FDA for the neoadjuvant treatment of breast cancer. The FDA also largely based the accelerated approval on data from the NeoSphere study.

In the NeoSphere study, the most common severe (grade 3 or higher) adverse events for pertuzumab plus trastuzumab and docetaxel were neutropenia (44.9%), febrile neutropenia (8.4%), leukopenia (4.7%), and diarrhea (5.6%).

Other significant adverse effects included decreased cardiac function, infusion-related reactions, hypersensitivity reactions, and anaphylaxis.