The Food and Drug Administration has granted regular approval to pertuzumab for use in combination with trastuzumab and chemotherapy as adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence.

Approval was based on data from APHINITY (NCT01358877), a multicenter, randomized, double-blind, placebo-controlled trial in 4804 patients with HER2-positive early breast cancer who had their primary tumour excised prior to randomization.

Patients were then randomized to receive pertuzumab or placebo, in combination with adjuvant trastuzumab and chemotherapy.

The main efficacy outcome was invasive disease-free survival (IDFS), 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.

After 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% (n=210) for those receiving placebo (HR 0.82; 95% CI: 0.67, 1.00; p=0.047).

High-risk patients included patients such as those with hormone receptor negative or those with node positive breast cancer.

The proportion of IDFS events in patients with hormone receptor negative disease was 8.2% (n=71) and 10.6% (n=91) in the pertuzumab and placebo arms, respectively (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). Overall survival data are not yet mature.

Adverse reactions reported in at least 30% of patients receiving pertuzumab in combination with trastuzumab and chemotherapy in APHINITY were diarrhoea, nausea, alopecia, fatigue, peripheral neuropathy, and vomiting.

The most common grade 3-4 adverse reactions (>2%) were neutropenia, febrile neutropenia, diarrhoea, neutrophil count decreased, anaemia, white blood cell count decreased, leukopenia, fatigue, nausea, and stomatitis.

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

Full prescribing information is available here.

Source: FDA