EMA Recommends Granting a Marketing Authorisation for Palbociclib

A novel treatment option for hormone receptor-positive, HER2–negative locally advanced or metastatic breast cancer

On 15 September 2016, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending granting a marketing authorisation for for the medicinal product palbociclib (Ibrance) for the treatment of women with locally-advanced or metastatic breast cancer that is hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)–negative.

The applicant for this medicinal product is Pfizer Limited.

Ibrance will be available as 75, 100 and 125 mg hard capsules. The active substance of Ibrance is palbociclib, a protein kinase inhibitor (ATC code: L01XE33) that is a highly selective, reversible inhibitor of cyclin-dependent kinases (CDK) 4 and 6. CDK4 and 6 are downstream of multiple signalling pathways which lead to cellular proliferation.

The approval was based on two studies showing that Ibrance in combination with letrozole (an aromatase inhibitor) or fulvestrant, significantly improves progression-free survival (PFS).

One of these two phase III trials compared treatment with palbociclib and letrozole with letrozole treatment alone. In this study, 444 patients who received palbociclib and letrozole had median PFS of 24.8 months, compared to 14.5 months in the group of 222 patients that received letrozole alone.

The other study is a phase III trial which compared treatment of fulvestrant together with palbociclib to treatment with only fulvestrant. In total 521 women were enrolled in this trial, regardless of their menopausal status. Preliminary results showed that 347 patients who received palbociclib and fulvestrant had a median PFS of 11.2 months compared to 4.6 months for 174 patients who only received fulvestrant.

The most common side effects are neutropenia, infections, leukopenia, fatigue, nausea, stomatitis, anaemia, alopecia, and diarrhoea.

The full indication is:

“Ibrance is indicated for the treatment of hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative locally advanced or metastatic breast cancer:

  • in combination with an aromatase inhibitor;
  • in combination with fulvestrant in women who have received prior endocrine therapy.

In pre- or perimenopausal women, the endocrine therapy should be combined with a luteinizing hormone releasing hormone (LHRH) agonist.”

It is proposed that treatment with Ibrance should be initiated and supervised by a physician experienced in the use of anticancer medicinal products.

Detailed recommendations for the use of this product will be described in the summary of product characteristics, which will be published in the European public assessment report and made available in all official European Union languages after the marketing authorisation has been granted by the European Commission.

The opinion adopted by the CHMP at its September 2016 meeting is an intermediary step on Ibrance’s path to patient access. The CHMP opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, a decision about price and reimbursement will then take place at the level of each Member State considering the potential role/use of the medicine in the context of the national health system of that country.

Breast cancer is the most common cancer in women worldwide, with nearly 1.7 million new cases diagnosed in 2012. In Europe, there were an estimated 464,000 new cases of breast cancer in 2012 and an estimated 131,000 deaths from the disease. Hormone receptor-positive breast cancer accounts for 65% of tumours in women aged 35 to 65 years and 82% of tumours in women older than 65 years.