The FDA has approved palbociclib (Ibrance, Pfizer) in combination with trastuzumab, with or without pertuzumab, and endocrine therapy for the maintenance treatment of hormone receptor-positive (HR+), HER2+ locally advanced or metastatic breast cancer following induction treatment.

In the phase 3 approval trial, PATINA, adding palbociclib to standard anti-HER2 and endocrine therapies for maintenance resulted in a 24% reduction in the risk for disease progression.

“Resistance to dual anti-HER2 and endocrine therapy remains a central clinical challenge for patients with HR+, HER2+ metastatic breast cancer — even after an excellent response to initial treatment,” said principal investigator Otto Metzger, MD, medical breast oncologist at the Dana-Farber Cancer Institute, in a Pfizer press release.

“Based on the results from the PATINA study, the addition of [palbociclib] in the maintenance phase can meaningfully extend the time patients go without their disease progressing,” he said.

Palbociclib was previously approved in combination with other medications for HR+, HER2- advanced or metastatic breast cancer. With the new approval, Pfizer said palbociclib becomes the first CDK4/6 inhibitor approved for HR+ metastatic disease regardless of HER2 status.

After induction treatment with a taxane and trastuzumab, PATINA randomized 518 patients evenly to either palbociclib or placebo on a background of trastuzumab, with or without pertuzumab, and endocrine therapy (fulvestrant or an aromatase inhibitor).

At a median follow-up of 53.5 months, median progression-free survival (PFS) was 44.3 months with palbociclib add-on vs 29.1 months according to the trial report. However, in a press release announcing the approval, FDA said that although there was a 24% improvement in investigator-assessed PFS, “median PFS could not be adequately described because of censoring.” Meanwhile, overall survival results are pending.

Grade 3 or worse neutropenia was reported in 61% of palbociclib patients in PATINA; the incidence of febrile neutropenia was 0.8%. A quarter of palbociclib patients had serious adverse reactions, including infections (8%), headache and pyrexia (1.5% each), and femur fracture (1.2%). Patients also experienced diarrhea, stomatitis, and fatigue.

Labeling warns of neutropenia, interstitial lung disease/pneumonitis, and embryo-fetal toxicity.

The recommended dosage is 125 mg orally once daily for 21 consecutive days, followed by 7 days off treatment.

M. Alexander Otto is a physician assistant and award-winning journalist. He is also an MIT science journalism fellow. Email: aotto@medscape.net.