New Drug
Aina Abell
On June 29, FDA approved Phesgo (Genentech) to treat adult patients with HER2-positive early stage and metastatic breast cancer. The drug, a combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf, can be administered in a treatment center or at home by a qualified health professional.
“Currently, most patients with HER2-positive breast cancer receive trastuzumab and pertuzumab at infusion centers. With a new administration route, Phesgo offers an outpatient option for patients to receive trastuzumab and pertuzumab,” said Richard Pazdur, MD, director of FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in FDA’s Center for Drug Evaluation and Research, in a statement.
Phesgo’s approval as a home treatment option comes as part of the agency’s wider efforts during the COVID-19 pandemic to “keep a strong focus on patients with cancer who constitute a vulnerable population at risk of contracting the disease,” said Pazdur. “At this critical time, we continue to expedite oncology product development.”
Indications and use
Phesgo is available in a single-dose vial and should be given subcutaneously as an injection in the thigh only. Its administration can take about 8 minutes for the initial loading dose and about 5 minutes for each subsequent dose—significantly faster than the standard I.V. treatment, which can take up to 150 minutes.
The medication can be used in combination with chemotherapy for neoadjuvant treatment of adult patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer and for adjuvant treatment of those at high risk for recurrence.
In combination with docetaxel, the drug is also indicated to treat patients with metastatic breast cancer who have not previously received anti-HER2 therapy or chemotherapy. Patients should be selected based on an FDA-approved companion diagnostic test.
Phesgo’s approval was based on the noninferiority Phase III study FeDeriCa, which found that in patients with HER2-positive early breast cancer, the medication’s efficacy and safety were comparable to those of I.V. pertuzumab and I.V. trastuzumab. However, patients taking Phesgo did experience higher administration-related reactions such as injection site reaction and/or pain, hypersensitivity, and anaphylaxis.
In addition, the PHranceSCa trial, a randomized, multicenter, multinational, open-label, crossover Phase II study, revealed that 85% of the 160 participating patients undergoing adjuvant treatment preferred Phesgo to the standard I.V. treatment.
Warnings and precautions
Phesgo’s prescribing information comes with a boxed warning for cardiomyopathy, embryo-fetal toxicity, and pulmonary toxicity.
Health care providers should evaluate patients’ cardiac function before and during treatment. According to the prescribing information, patients taking the medication in conjunction with anthracycline-containing chemotherapy regimens are at highest risk of experiencing subclinical and clinical cardiac failure.
Exposure to Phesgo can be harmful to a developing fetus or a newborn baby and may lead to embryo-fetal death and birth defects, including pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Health professionals should warn patients who are pregnant about these risks. Pharmacists and other providers should also counsel patients of reproductive age to use effective contraception during treatment and for 7 months after their last dose. Parents who are breastfeeding should talk to their provider about either discontinuing breastfeeding or discontinuing treatment.
Health professionals should be on the lookout for signs of pulmonary toxicity in patients taking Phesgo. If patients experience anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome, stop treatment immediately and monitor the patient until symptoms completely resolve.
Common adverse effects
The most common adverse effects for patients taking Phesgo with chemotherapy for treatment of early breast cancer are alopecia, nausea, diarrhea, anemia, and asthenia. These adverse effects, along with fatigue, rash, and peripheral neuropathy, are also common in patients taking Phesgo with docetaxel for metastatic breast cancer.
The medication can exacerbate chemotherapy-induced neutropenia, so health care providers should monitor patients for any signs of new or worsening infections.
If patients experience adverse effects or are exposed to Phesgo during pregnancy, pharmacists should encourage them to contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.