The UK National Institute for Health and Care Excellence has approved palbociclib in combination with fulvestrant for the treatment of female patients with hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer who have received prior endocrine therapy.
The UK National Institute for Health and Care Excellence (NICE) has approved palbociclib (Ibrance) in combination with fulvestrant (Faslodex) for the treatment of female patients with hormone receptor (HR)—positive, HER2-negative locally advanced or metastatic breast cancer who have received prior endocrine therapy.1
The approval, which allows the combination to be available on the National Health Service (NHS) via the Cancer Drugs Fund (CDF), is based on data from the phase III PALOMA-3 trial, in which palbociclib added to fulvestrant led to a median progression-free survival (PFS) of 11.2 months compared with 4.6 months with fulvestrant alone in female patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer who received prior hormonal therapy (HR, 0.50; 95% CI, 0.40—0.62; P <.000001).2,3
“Clinical trial evidence suggests that, compared with fulvestrant alone, palbociclib with fulvestrant increases the length of time before the disease progresses in people who have had previous endocrine treatment,” NICE stated in its appraisal document announcing the recommendation of the combination regimen.
In the double-blind PALOMA-3 study, 521 patients with advanced breast cancer whose disease progressed on or following endocrine treatment were randomized 2:1 to standard 500 mg of fulvestrant plus either 125 mg of daily oral palbociclib (n = 347) every 3 weeks or placebo (n = 174). Women were eligible for enrollment regardless of menopausal status.
In earlier findings published in Lancet Oncology,4 the median PFS was 9.5 months with palbociclib/fulvestrant compared with 4.6 months for fulvestrant alone (HR, 0.46; 95% CI, 0.36-0.59; P <.0001). These initial data were the basis for the FDA’s February 2016 approval for palbociclib in combination with fulvestrant for the treatment of women with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy.
However, in June 2018, Pfizer, the manufacturer of palbociclib, reported that the combination failed to improve OS versus fulvestrant/placebo in PALOMA-3 for patients with HR-positive, HER2-negative metastatic breast cancer who received prior endocrine therapy. OS was a secondary endpoint of the study.
Then, at a median follow-up of 44.8 months in the intent-to-treat population, the palbociclib/fulvestrant combination demonstrated a median OS improvement of 6.9 months over fulvestrant plus placebo (stratified HR, 0.81; 95% CI 0.64-1.03; 1-sided P = .043). The median OS with palbociclib/fulvestrant was 34.9 months (95% CI, 28.8-40.0) versus 28.0 months (95% CI, 23.6-34.6) with fulvestrant/placebo. In addition to the stratified HR for OS, researchers also reported an unstratified HR for OS of 0.79 (95% CI, 0.63-1.00; 1-sided P = 0.246).
Results also were stratified by patients who had sensitivity to prior endocrine therapy. In patients with sensitivity, the median OS was 39.7 months (95% CI, 34.8-45.7) for those who were treated with palbociclib/fulvestrant (n = 274) and 29.7 months (95% CI, 23.8-37.9) for those who received placebo/fulvestrant (n = 136; HR, 0.72; 95% CI, 0.55-0.94; 1-sided P = .0081).
In patients without sensitivity to prior endocrine therapy, the median OS was 20.2 months (95% CI, 17.2-26.4) on the palbociclib/fulvestrant arm (n = 73) and 26.2 months (95% CI, 17.5-31.8) for those treated with placebo/fulvestrant (n = 38; HR, 1.14; 95% CI, 0.71-1.84; 1-sided P = .2969).
Moreover, median OS improved significantly by 11.5 months in patients without visceral disease; it was 46.9 months (95% CI, 39.3-not estimable [NE]) with palbociclib/fulvestrant and 35.4 months (95% CI, 24.6-NE) with fulvestrant/placebo (HR, 0.69; 95% CI, 0.46-1.04).
Treatment with palbociclib also did not interfere with the type or efficacy of standard treatment following disease progression, and no new safety signals were observed with the additional follow-up.
The FDA initially granted palbociclib an accelerated approval in February 2015 in combination with letrozole as a frontline treatment for postmenopausal women with estrogen receptor—positive, HER2-negative metastatic breast cancer. A full approval for that indication was granted by the agency in March 2017.
In April 2019, the FDA expanded the approval of palbociclib capsules in combination with endocrine therapy to include male patients with HR-positive, HER2-negative advanced or metastatic breast cancer.