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The European Commission ( EC ) has approved Ibrance ( Palbociclib ) for the treatment of women with hormone receptor-positive, human epidermal growth factor receptor 2-negative ( HR+/HER2- ) locally advanced or metastatic breast cancer.
The approval is for Ibrance to be used in combination with an aromatase inhibitor.
The approval also covers the use of Ibrance in combination with Fulvestrant in women who have received prior endocrine therapy.

Ibrance is the first medicine to be approved in Europe that works by inhibiting cyclin-dependent kinases 4 and 6 ( CDK 4/6 ). It also is the first new medicine approved for the treatment of women with this type of metastatic breast cancer in the first-line setting in nearly 10 years.
Women with HR+/HER2- metastatic breast cancer represent about 60% of all metastatic breast cancer cases.

The EC approval is based on a robust submission package including results from the phase 2 PALOMA-1 trial in postmenopausal women with estrogen receptor-positive ( ER+ )/HER2- metastatic breast cancer who had not received prior systemic therapy for their advanced disease, the phase 3 PALOMA-2 trial in the same population and the phase 3 PALOMA-3 trial in women with HR+/HER2- metastatic breast cancer who had progressed on prior endocrine therapy.
All three randomized trials demonstrated that Ibrance in combination with an endocrine therapy significantly prolonged progression-free survival compared to endocrine therapy alone or endocrine therapy with placebo.

Breast cancer is the most common invasive cancer among women in Europe, with more than 464,200 new cases and 131,260 deaths per year. Up to 30% of women diagnosed with and treated for early breast cancer will go on to develop metastatic breast cancer, which occurs when the cancer spreads beyond the breast to other parts of the body.
There is no cure for metastatic breast cancer, and patients are in need of new treatment options that help keep their cancer from worsening, manage symptoms and help them maintain quality of life for as long as possible.

Ibrance Pivotal Trials

PALOMA-1 :: The phase 2 PALOMA-1 trial evaluated Palbociclib in combination with Letrozole compared with Letrozole alone as a first-line, or initial, therapy in 165 postmenopausal women with ER+/HER2- advanced breast cancer who had not received previous systemic treatment for their advanced disease.
The combination of Palbociclib plus Letrozole significantly prolonged progression-free survival compared to Letrozole alone ( hazard ratio, HR=0.488 [ 95% CI: 0.319–0.748 ] ), with the median progression-free survival of 20.2 months ( 95% CI: 13.8–27.5 ) in the Palbociclib arm compared to 10.2 months ( 95% CI: 5.7–12.6 ) in women who received Letrozole alone.
The most common adverse events ( greater than or equal to 20% ) of any grade reported in patients treated with Palbociclib plus Letrozole versus Letrozole alone included neutropenia ( 75% vs 5% ), leukopenia ( 43% vs 3% ), fatigue ( 41% vs 23% ), anemia ( 35% vs 7% ), upper respiratory infection ( 31% vs 18% ), nausea ( 25% vs 13% ), stomatitis ( 25% vs 7% ), alopecia ( 22% vs 3% ) and diarrhea ( 21% vs 10% ).

PALOMA-2 :: The phase 3 PALOMA-2 trial evaluated Palbociclib in combination with Letrozole compared with Letrozole plus placebo as a first-line treatment in 666 postmenopausal women with ER+/HER2- metastatic breast cancer, the same patient population as PALOMA-1.
The combination of Palbociclib plus Letrozole resulted in a statistically significant improvement in progression-free survival ( HR=0.58 [ 95% CI: 0.46–0.72 ], P less than 0.000001 ), with a median progression-free survival of 24.8 months compared to 14.5 months for those who were treated with Letrozole plus placebo.
The most common adverse events ( greater than or equal to 20% ) of any grade reported in patients treated with Palbociclib plus Letrozole versus Letrozole plus placebo included neutropenia ( 79.5% vs 6.3% ), fatigue ( 37.4% vs 27.5% ), nausea ( 35.1% vs 26.1% ), arthralgia ( 33.3% vs 33.8% ) and alopecia ( 32.9% vs 15.8% ).

PALOMA-3 :: The phase 3 PALOMA-3 trial evaluated Palbociclib in combination with Fulvestrant compared with placebo plus Fulvestrant in 521 women with HR+/HER2- metastatic breast cancer, regardless of menopausal status, whose disease progressed on or after prior endocrine therapy.
The combination of Palbociclib plus Fulvestrant substantially improved progression-free survival compared to Fulvestrant plus placebo ( HR=0.461 [ 95% CI: 0.360–0.591 ), P less than 0.0001 ), with a median progression-free survival of 9.5 months ( 95% CI: 9.2–11.0 ) in the Palbociclib arm compared to 4.6 months ( 95% CI: 3.5–5.6 ) in women who received placebo plus Fulvestrant.
The most common adverse events ( greater than or equal to 20% ) of any grade reported in PALOMA-3 of Palbociclib plus Fulvestrant versus placebo plus Fulvestrant included neutropenia ( 83% vs 4% ), leukopenia ( 53% vs 5% ), infections ( 47% vs 31% ), fatigue ( 41% vs 29% ), nausea ( 34% vs 28% ), anemia ( 30% vs 13% ), stomatitis ( 28% vs 13% ), headache ( 26% vs 20% ), diarrhea ( 24% vs 19% ), thrombocytopenia ( 23% vs 0% ) and constipation ( 20% vs 16% ). ( Xagena )

Source: Pfizer, 2016

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