Palbociclib gets early FDA approval for breast cancer

22 Feb 2016

On February 19, 2016, the US FDA approved palbociclib (Ibrance Capsules, Pfizer) in combination with fulvestrant for the treatment of women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following endocrine therapy.

In February 2015, FDA granted accelerated approval for palbociclib in combination with letrozole for the treatment of HR-positive, HER2-negative advanced breast cancer as initial endocrine based therapy in postmenopausal women.

Details of the clinical trial

The approval is based on the demonstration of an improvement in progression-free survival in an international, randomized, double-blind, parallel group, multicenter study comparing palbociclib plus fulvestrant to placebo plus fulvestrant. Women enrolled had HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression on or after prior adjuvant or metastatic endocrine therapy.

In particular, for the clinical trial:

  • A total of 521 pre- and postmenopausal women were randomized (2:1) to either palbociclib plus fulvestrant or placebo plus fulvestrant until disease progression or unacceptable toxicity.
  • Palbociclib was administered orally at a dose of 125 mg daily for 21 consecutive days followed by 7 days off treatment.
  • Fulvestrant was administered intramuscularly at a dose of 500 mg on days 1, 15, 29 and once monthly thereafter.
  • Pre- or perimenopausal women were enrolled in the study and received the LHRH agonist, goserelin, for at least 4 weeks prior to and for the study’s duration.
  • Among the 521 patients, 80% were postmenopausal, all patients had received prior systemic therapy, and 75% had received a previous chemotherapy regimen.
  • 25% had not received prior therapy for metastatic disease, 60% had visceral metastases, and 23% had bone only disease.


Adverse events and reactions

The study demonstrated an improvement in progression-free survival. In particular, the median progression-free survival was 9.5 versus 4.6 months for patients treated in the palbociclib plus fulvestrant and placebo plus fulvestrant arms, respectively. Safety data was evaluated in 345 patients who received palbociclib plus fulvestrant.

The most common (greater than or equal to 10%) of grade 1-4 adverse reactions were neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, headache, diarrhea, thrombocytopenia, constipation, vomiting, alopecia, rash, decreased appetite, and pyrexia.

The most common (greater than or equal to 5%) grade 3-4 adverse reactions were neutropenia (66%) and leukopenia (31%). The most frequently reported serious adverse reactions in patients receiving palbociclib plus fulvestrant were infections, pyrexia, neutropenia, and pulmonary embolism).

Dosing of the drug

Dose reductions due to an adverse reaction of any grade occurred in 36% of patients and permanent discontinuation associated with an adverse reaction occurred in 6% of patients.

The recommended dose and schedule of palbociclib is 125 mg daily for 21 consecutive days followed by 7 days off treatment in combination with fulvestrant treatment. The dose and schedule of fulvestrant is 500 mg intramuscularly on days 1, 15, 29 and once monthly thereafter.

Palbociclib is being approved prior to the Prescription Drug User Fee Act (PDUFA) goal date of April 15, 2016.This application was granted Priority Review and Breakthrough Therapy Designation

Source: eCancer News

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