FDA Grants Approval to Pertuzumab for Adjuvant Treatment in Patients With HER2-Positive Breast Cancer

The FDA has granted approval to pertuzumab (Perjeta) to be used in combination with trastuzumab (Herceptin) and chemotherapy as adjuvant therapy for the treatment of patients with HER2-positive early breast cancer with a high risk of recurrence.

In 2013, the FDA granted accelerated approval to pertuzumab as neoadjuvant treatment. This latest adjuvant approval fulfills the accelerated approval postmarketing process, and regular approval is now granted for pertuzumab as part of treatment for patients with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer (either greater than 2 cm in diameter or node-positive).

The full approval of Roche subsidiary Genentech’s pertuzumab comes after publication of data from the APHINITY (NCT01358877) trial. The multicenter, randomized double-blind, placebo-controlled trial included 4804 patients with HER2-positive early breast cancer who had their primary tumor removed prior to randomization. Following tumor removal, the patients were randomized to receive either pertuzumab or placebo in combination with adjuvant trastuzumab and chemotherapy.

The initial pertuzumab dose is 840 mg administered as a 60-minute intravenous infusion, followed by 420 mg administered as a 30- to 60-minute intravenous infusion every 3 weeks after.

The authors assessed for invasive disease-free survival (IDFS), which was defined as the time from randomization to first occurrence of ipsilateral local or regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, or death from any cause.

After0 a median follow-up of 45.4 months, the proportion of IDFS events in the intent-to-treat population was 7.1% (n = 171) in the pertuzumab arm and 8.7% for those administered placebo (hazard ratio [HR], 0.82; 95% Cl, 0.67-1.00; P = .047). Patients with hormone receptor—negative or node-positive breast cancer were considered high-risk patients.

The proportion of IDFS events in patients with hormone receptor—negative disease was 8.2% (n = 71) in the pertuzumab arm and 10.6% (n = 91) in the placebo arm (HR, 0.76; 95% CI, 0.56-1.04). The proportion of IDFS events for patients with node-positive disease was 9.2% (n = 139) and 12.1% (n = 181) in the pertuzumab and placebo arms, respectively (HR, 0.77; 95% CI, 0.62-0.96).

Adverse reactions reported in at least 30% of patients who received pertuzumab included diarrhea, nausea, alopecia, and fatigue. The most common grade 3 to 4 adverse reactions included neutropenia, febrile neutropenia, and leukopenia.

“The goal of treating breast cancer early is to provide people with the best chance for a cure. While we come closer to this goal with each advance, many people still have a recurrence and progress to the metastatic stage,” said Sandra Horning, MD, Roche's Chief Medical Officer and Head of Global Product Development, in a statement. “Today’s approval of Perjeta means people with HER2-positive early breast cancer at high risk of recurrence have a new, clinically meaningful treatment option to reduce the chances of their disease returning.”

In 2012, the FDA granted regular approval to pertuzumab for its use in combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer who had not received prior anti-HER2 therapy or chemotherapy for metastatic disease.