Despite the great strides that have been made in the management of early BC, advanced-stage BC has a 3- and 5-year survival rate of only 35% to 55% and 25%, respectively. First-line therapy for hormone receptor-positive/human epidermal growth factor receptor-2–negative advanced breast cancer (ABC) includes palbociclib, a cyclin-dependent kinase 4/6 inhibitor, in combination with an aromatase inhibitor or in combination with fulvestrant, an estrogen receptor antagonist. While the PALOMA-3 clinical trial found a significant difference in the primary outcome of progression-free survival among those treated with palbociclib plus fulvestrant (PF) versus placebo fulvestrant, real-world data are lacking.
Investigators conducted a retrospective cohort study to evaluate the effectiveness of PF in the real-world clinical setting during the period of early access to palbociclib in patients with ABC. Using data from the Portuguese National Cancer Registry, a nationwide population-based cancer registry, investigators were able to gather information from the time of a patient's initial diagnosis until their death. This information was coordinated with data from the PF early access program database through the National Authority of Medicine and Health Products. Additional data were obtained from hospital pharmacy databases for those patients who were treated at private health institutions and who were not included in the early access program.
The study population consisted of adults aged 18 years or older with ABC (stages IIIc and IV) who were initiated on PF between May 31, 2017, and March 31, 2019. Patients were followed until either their death or the study cut-off date, which was February 28, 2021.
The primary outcome was real-world progression-free survival (rwPFS), which was calculated as the time elapsed between PF initiation and disease progression or death. Secondary outcomes included real-world overall survival (rwOS), which was the time elapsed between PF initiation and death due to any cause; real-world time to PF failure (rwTPF), which was the time from PF initiation to date of treatment discontinuation due to any cause; and real-world time to next treatment (rwTTNT), which was defined as the time from PF initiation to the initiation of a new treatment line for ABC.
Further subanalysis of women was based on menopausal status with women aged 50 years or younger classified as pre/perimenopausal and women aged older than 55 years considered postmenopausal. For those women aged 51 to 55 years, menopausal classification varied depending on the use of a luteinizing hormon–releasing hormone agonist with subjects on this agent considered pre/perimenopausal and those not receiving the hormonal agent considered postmenopausal.
Two-hundred and ten patients were included in the study—208 females and two males. The median age of the study population was 58 years. Almost 70% of the women studied were postmenopausal. Metastatic disease included visceral involvement (i.e., lung/pleura, liver, peritoneum or brain metastases) in 55.3%. Mean follow-up was approximately 2 years (23.22 months). Chemotherapy was utilized as first-line in 101 (71.1%), second-line in 75 (88.2%), and third-line in 43 (89.6%). Other less commonly used agents included endocrine therapy, targeted therapy, mammalian target of rapamycin inhibitors, phosphoinositide 3-kinase inhibitors, and poly (ADP-ribose) polymerase inhibitors.
Investigators found that the median treatment duration was 7.48 months (interquartile range: 3.75-15.72). About 85% initiated treatment with 125 mg of palbociclib, which is the recommended dose, although 43.2% required a dose reduction. At the time of study discontinuation, 90% of patients had discontinued treatment, most commonly due to disease progression (80.4%); 3.7% had died. There were 12 hematologic events that led to discontinuation in 8.99%; these included neutropenia (5), pantocytopenia (3), bicytopenia (3), and thrombocytopenia (1).
Median rwPFS was 7.43 months with a 2-year rwPFS of 16.65%. Median rwOS was 24.7 months, and median rwTPF was 7.5 months with a 2-year rwTPF of 17.09% and a median rwTTNT of 11.74 months. rwOS was higher in those with a better performance status and those with nonprimary endocrineÐresistant disease. Poorer ECOG performance status (>2) and >3 prior lines of endocrine therapy were independent risk factors for disease progression (HR = 1.73, 95% CI 1.04-2.88 and HR = 2.87, 95% CI 1.39-5.92, respectively). For patients with visceral metastatic disease and an ECOG PS >2, the risk of death was increased compared with those who had bone-only metastases and have a good performance status (ECOG PS 0-1). Age was not a factor in outcome.
It should be noted that in clinical trials, median PFS was 9.5 months and median OS was 34.9 months.
The authors concluded that while PF seems to be an effective treatment for advanced BC, its benefit in rwPFS and rwOS was shorter in the real-life setting compared with clinical trials. Pharmacists should be aware of these limitations of treatment in order to provide a realistic expectation of benefit for their patients with advanced BC who are being treated with PF.
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