Perjeta by Genentech, Inc

Perjeta (pertuzumab) is now approved for the neoadjuvant treatment of breast cancer.

On September 30, 2013, the FDA announced approval of Perjeta (pertuzumab), an intravenously administered HER2/neu receptor antagonist, for neoadjuvant treatment of breast cancer.¹ This indication joins an earlier indication of Perjeta for treatment of HER2-positive late-stage (metastatic) breast cancer as part of a treatment regimen including trastuzumab and docetaxel.² Perjeta carries a black box warning for cardiomyopathy, including subclinical and clinical heart failure, and embryofetal toxicity, including embryofetal death and birth defects. Use of Perjeta is contraindicated in patients with hypersensitivity to the active ingredient in Perjeta or any inactive ingredients in the formulation.³

Pharmacology and Pharmacokinetics

Perjeta blocks subdomain II of the extracellular dimerization domain of human epidermal growth factor receptor 2 protein (HER2), preventing heterodimerization of HER2 with other receptors in the family of HER receptors. In this way, Perjeta reduces activation of intracellular signaling pathways, slows or stops the growth of cells, and promotes cell apoptosis. Pertuzumab may also augment the activity of trastuzumab by modulating antibody-dependent cell-mediated cytotoxicity.³

In 481 patients receiving Perjeta with an initial dose of 840 mg and a maintenance dosage of 420 mg administered every 3 weeks, the median half-life was 18 days. Because age, gender, ethnicity, disease status, serum albumin levels, and lean body weight did not affect pharmacokinetic parameters to a large degree, dose adjustments for body weight and baseline albumin levels are not necessary.³

Dosage and Administration

Perjeta is supplied in 14-mL vials at a concentration of 30 mg/mL, and should be stored in the carton to protect the solution from light at a temperature between 36°F and 46°F prior to preparation. Perjeta should be administered as an intravenous (IV) infusion, and should not be administered via IV push or as a bolus injection.³

Patients initiating Perjeta treatment receive an initial dose of 840 mg infused over 60 minutes. Subsequent doses of 420 mg, infused over 30 to 60 minutes, are administered every 3 weeks. Patients receiving Perjeta as neoadjuvant therapy typically receive 3 to 6 doses at 3-week intervals, whereas patients with metastatic breast cancer typically continue treatment indefinitely.³

No dosage adjustment is necessary in patients with mild to moderate renal impairment. Limited data are available for patients with severe renal impairment, and the manufacturer reports that no dose adjustment recommendation can be made based on this data. The effect of hepatic impairment on the pharmacokinetics of Perjeta has not been evaluated in clinical studies.³

Clinical Trials

Scientists evaluated the safety and efficacy of Perjeta as neoadjuvant therapy in patients with operable, locally advanced, or inflammatory HER2-positive breast cancer through a multicenter, randomized trial in 417 patients randomized to trastuzumab/docetaxel therapy, pertuzumab/trastuzumab/docetaxel therapy, pertuzumab/trastuzumab therapy, or pertuzumab/docetaxel therapy. Triple therapy led to pathological complete response (pCR) in 39.3% of patients versus averages ranging from 11.2% to 21.5% of patients with other regimens. The rate of pCR with triple therapy was significantly better than the rate observed in the group with the next-highest rate of pCR (P = .0063). Overall survival and progression-free survival data are not available.^3,4

Warnings and Precautions

Investigators did not identify any drug interactions between Perjeta and its companion chemotherapies, trastuzumab and docetaxel. Perjeta is a Pregnancy Category D medication, and has been shown to cause oligohydramnios, delays in kidney development, and embryofetal death in pregnant cynomolgus monkeys. No adequate and well-controlled studies have been conducted in pregnant women. If a pregnant woman is exposed to Perjeta, call the Genentech Adverse Event Line (1-888-835-2555) and encourage the patient to enroll in the MotHER Pregnancy Registry (1-800-690-6720). Scientists are unsure if Perjeta is present in human breast milk.³

Serious adverse events associated with use of Perjeta include embryofetal toxicity, left ventricular dysfunction, infusion-related reactions, and hypersensitivity reactions or anaphylaxis. In patients receiving Perjeta, trastuzumab, and docetaxel as neoadjuvant treatment of breast cancer, alopecia, diarrhea, nausea, and neutropenia were the most common adverse events, each of which occurred in more than 30% of patients receiving Perjeta. For a complete discussion of potential adverse events and drug interactions with Perjeta, please consult the product package insert.³ SPT

References

• US Food and Drug Administration. FDA approves Perjeta for neoadjuvant breast cancer treatment [press release]. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm370393.htm. Accessed October 2014.
• US Food and Drug Administration. FDA approves Perjeta for type of late-stage breast cancer [press release]. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm307549.htm. Accessed October 2014.
• Perjeta (pertuzumab) [package insert]. South San Francisco, CA: Genentech, Inc; 2013.
• Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25-32.