The addition of palbociclib to the hormonal therapy fulvestrant resulted in an increase of 5.4 months in the delay of disease progression compared with fulvestrant alone in women with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer. The results of the phase III PALOMA3 trial were presented (abstract LBA502) at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting held May 29 to June 2 in Chicago.
The primary endpoint of this trial was progression-free survival (PFS). The median PFS was 9.2 months in the combination therapy arm compared with 3.8 months in the hormonal therapy alone arm (hazard ratio, 0.422; P < .000001).
“Palbociclib in combination with fulvestrant more than doubled disease control compared to fulvestrant alone, and was well tolerated,” said Nicholas C. Turner, MD, an academic consultant medical oncologist at the Royal Marsden and a clinician at the Institute of Cancer Research in London. “[This shows] an effective treatment option for these women when their cancer progressed on prior endocrine therapy.”
The US Food and Drug Administration (FDA) approved palbociclib in combination with letrozole following initial endocrine-based therapy for postmenopausal women with ER-positive, HER2-negative metastatic breast cancer. The drug is an oral cyclin-dependent kinase (CDK) 4/6 inhibitor.
Benefit from the addition of palbociclib was seen in both pre- and postmenopausal women. Twenty-one percent of women in the study were premenopausal. According to the study authors, this is one of the first trials that tested targeted therapy plus hormonal therapy for advanced breast cancer in younger, premenopausal patients.
Turner and colleagues randomized 521 patients 2:1 to receive either 125 mg daily of palbociclib for a 3-week on, 1-week off cycle plus the standard-of-care 500-mg injection of fulvestrant, or fulvestrant plus placebo. Pre- and perimenopausal women also received goserelin. Patients had received, at most, one prior chemotherapy regimen for metastatic disease.
The median age of patients was 57 and 56 years. Sixty percent of patients had visceral metastases, and 79% had responded to prior hormonal therapy. One-third of the patients had prior chemotherapy.
“Consistent benefit from palbociclib was seen in all subgroups analyzed, with the same benefit in both premenopausal and postmenopausal women,” Turner told Cancer Network. “Future research will look for markers that might predict who benefits most.”
The combination was well tolerated overall, with 2.0% and 1.7% of patients stopping therapy due to side effects in the palbociclib and control arms, respectively. The most frequent adverse event that caused patients to stop therapy was neutropenia, which occurred in 78.8% of patients treated with palbociclib, compared with only 3.5% in the control arm. Rates of leukopenia were 45.5% and 4.1% and rates of fatigue were 38.0% and 26.7% in the combination and control arms, respectively.
According to Turner, although low blood counts were seen frequently in blood tests, this led to few symptoms for patients and is not a major concern. “The rate of serious infections with low blood counts, called febrile neutropenia, was very low, occurring in only 0.6% of patients, no higher than was seen with placebo,” he added.
Patients continue to be followed for overall survival and quality-of-life measures.