Palbociclib Extends Survival in Advanced Breast Cancer

Results from the PALOMA-3 trial suggest that adding an inhibitor of the cyclin-dependent kinases (CDK) 4 and 6 to standard hormonal therapy can significantly delay disease progression in women with advanced hormone receptor (HR)–positive, HER2-negative breast cancer whose disease progressed during endocrine therapy. The results were presented on May 30 at the American Society of Clinical Oncology Annual Meeting in Chicago, IL, and subsequently published in The New England Journal of Medicine.

In the phase III study, 521 pre- and postmenopausal women with HR-positive, HER2-negative advanced metastatic breast cancer were randomized 2:1 to receive either the CDK4/6 inhibitor palbociclib (Ibrance; Pfizer) in combination with fulvestrant (Faslodex; MedImmune) or fulvestrant alone. At data cutoff in December 2014, progression-free survival (PFS) was 9.2 months in the intervention group compared with 3.8 months in the control group, prompting investigators to stop the trial early for efficacy.

“Previous studies have shown that palbociclib is active in endocrine-sensitive breast cancer, and this study confirms that as tumors become resistant to endocrine therapy, CDK4/6 is still a target,” said the study's lead author Nicholas Turner, MD, PhD, consultant medical oncologist at the Royal Marsden Hospital and a team leader at the Institute of Cancer Research in London, UK. “Palbociclib more than doubled PFS and very few patients had to stop due to side effects, which will be key as palbociclib moves forward in the clinic.”

The CDK4/6 proteins play a critical role in causing HR-positive breast tumors to proliferate. Results from earlier studies suggest that combining CDK4/6 inhibitors with hormonal therapy can improve outcomes, whether or not women have received prior endocrine therapy. In February, the FDA granted accelerated approval to palbociclib combined with letrozole as first-line treatment for postmenopausal women with advanced ER-positive, HER2-negative breast cancer who have not received prior endocrine therapy, based on results from the phase II PALOMA-1 trial. A confirmatory phase III trial, PALOMA-2, is ongoing.

The PALOMA-3 findings suggest that taking palbociclib may allow women to delay undergoing chemotherapy—typically the next step when initial hormonal therapy stops working—and suffering its side effects, said Turner. Palbociclib, taken orally, was well tolerated, with only 2.6% of patients in the study having to stop taking it due to adverse events. The most common side effects associated with palbociclib were neutropenia (78% versus 3.5% in control group) and leukopenia (46% versus 4%).

The results confirm that combination therapy with palbociclib is an effective treatment option for this population of patients going forward, said Don Dizon, MD, clinical co-director of gynecologic oncology at Massachusetts General Hospital in Boston.

“The PALOMA-3 results are incredibly important for women with HR-positive, HER2-negative breast cancer,” said Dizon. “This represents a new standard-of-care option, particularly after progression of disease from prior endocrine therapy.”