Data from a retrospective analysis confirm the benefit of palbociclib plus an aromatase inhibitor in elderly patients with hormone receptor–positive, HER2-negative advanced/metastatic breast cancer.
Real-world data for progression-free survival (PFS), overall survival (OS), and time to chemotherapy (TTC) were significantly improved among patients 75 years and older with hormone receptor–positive, HER2-negative advanced/metastatic breast cancer who were treated with the first-in-class CDK4/6 inhibitor palbociclib (Ibrance) with an aromatase inhibitor compared with those who received an aromatase inhibitor alone. Investigators concluded that these data support the use of the combination therapy as a standard-of-care for the first-line treatment of patients in this subgroup.1
Data from a retrospective analysis (NCT05361655) were presented in a poster at the 40th Annual Miami Breast Cancer Conference®. The study was conducted using Flatiron Health’s nationwide longitudinal database which identified 961 patients that fit the analysis’ criteria.1 The combination was granted accelerated approval in 2015 and full approval in 2017 based on data from the PALOMA-2 trial (NCT01740427).2
Among the population, 32.6% (n = 313) of patients received palbociclib in combination with an aromatase inhibitor and 67.4% (n = 648) received an aromatase inhibitor alone.1
Stabilized inverse probability treatment weighting (sIPTW) was used to balance patient characteristics. However, investigators were not able to adjust for the effects of potential unmeasured confounders, and a 1:1 propensity score matching (PSM) was used as sensitivity analysis.1
The real-world median PFS in the unadjusted analysis was 20.5 months (95% CI, 17.5-27.3) for patients in the combination group and 14.9 months (95% CI, 12.9-16.6) for patients receiving an aromatase inhibitor alone (HR, 0.69; 95% CI, 0.57–0.83; P = .0001). Similarly, real-world median PFS was 20.0 months (95% CI, 15.7-26.7) and 15.0 months (95% CI, 12.9-16.8), respectively, after the sIPTW analysis (HR, 0.72; 95% CI, 0.59-0.89; P = .0021). The real-world median PFS was 20.0 months (95% CI, 16.5-29.9) and 15.8 months (95% CI, 13.1-18.4), respectively, after the PSM analysis (HR, 0.73; 95% CI, 0.57-0.92; P = .0094).1
Additional findings showed that patients who received the combination experienced a median OS of 47.8 months (95% CI, 40.7-not reached [NR] vs 31.8 months (95% CI, 27.9-37.7) for those who received only an aromatase inhibitor in the unadjusted group (HR, 0.60; 95% CI, 0.48-0.74; P < .0001). Median OS was 43.0 months (95% CI, 40.1-NR) and 32.4 months (95% CI, 28.2-38.2), respectively, after the sIPTW analysis (HR, 0.66; 95% CI, 0.5-0.84; P = .0007) and median OS was 49.0 months (95% CI, 40.7-NR) and 37.3 months (95% CI, 29.4-44.4), respectively, after the PSM analysis (HR, 0.64; 95% CI, 0.49-0.85; P = .0018).
The median TTC was 40.0 months (95% CI, 33.8-42.8) with palbociclib and an aromatase inhibitor and 26.3 months (95% CI, 23.2-29.6) with an aromatase inhibitor alone in the unadjusted analysis (HR, 0.66; 95% CI, 0.55-0.81; P < .0001). After the sIPTW analysis, the median TTC was 40.2 months (95% CI, 33.8-42.9) and 27.4 months (95% CI, 23.4-30.9), respectively, (HR, 0.69; 95% CI, 0.55-0.87; P = .0014), and median TTC after the PSM analysis was 41.3 months (95% CI, 35.0-56.8) and 32.7 months (95% CI, 23.9-41.4), respectively, (HR, 0.72; 95% CI, 0.55-0.93; P = .0125).
To conduct their analysis, investigators identified patients who received the combination or monotherapy between February 2015 and March 2020, as data are limited comparing these treatments in this subgroup of patients, with evaluation occurring until whichever came first: the data cutoff date of September 30, 2020, death, or last visit.1
Limitations of the analysis included that there may be potential bias in treatment selection, missing or incomplete data, limited data on comorbidities, there was a possibility for inaccurate data as this data was evaluated from a retrospective database, and results may not be generalizable to patients outside of Flatiron’s network.
An additional limitation noted by the investigators included that “disease progression was not assessed as scheduled in clinical trials and was not based on Response Evaluation Criteria in Solid Tumors; therefore, the data are limited by each treating clinician’s interpretation of radiographic scans or pathology results.”
Prior to adjustments, the median follow-up was 23.7 months for the combination arm and 21.4 months for the monotherapy group. There were 306 patients with documented palbociclib doses, 75.2% received 125 mg daily, and 39.5% had a dose adjustment. Patients had a median age of 80.0 years in both arms and baseline characteristics were generally balanced after sIPTW and PSM evaluations.1
Patients in the unadjusted cohort who received the combination had metastatic breast cancer at stages of I, II, III, IV, and not documented at rates of 12.8%, 24.9%, 8.3%, 42.5%, and 11.5% in the combination group and at rates of 14.4%, 23.5%, 13.4%, 33.8%, and 15.0% in the monotherapy group, respectively. Patients had visceral disease (33.9% and 26.2%), bone-only metastasis (39.3% and 39.0%), brain metastases (1.3% and 1.9%), and a mean National Cancer Institute comorbidity index (0.6% and 0.6%) in the combination and monotherapy arms, respectively. The number of metastatic sites in the investigative and control groups were 1 (47.9% and 55.1%), 2 (27.2% and 19.9%), 3 (13.7% and 8.2%), 4 (2.6% and 2.0%), 5 or more (3.5% and 1.2%), and not documented (5.1% and 13.6%), respectively.1
In the unadjusted cohort, the disease-free interval f was de novo metastatic breast cancer (42.5% and 33.8%), a year or less (1.6% and 4.0%), more than 1 to 5 years (11.8% and 21.5%), more than 5 years (44.1% and 40.3%), and not documented (0.0% and 0.5%) in the combination and monotherapy arms, respectively. ECOG performance status was 0 (31.3% and 19.6%), 1 (27.8% and 21.0%), 2,3,or 4 (16.9% and 24.7%), and not documented (24.0% and 34.7%), respectively.1
The analysis defined real-world PFS as the number of months from starting treatment to death or disease progression, which was assessed by the treating clinician based on radiology, tissue biopsy, laboratory evidence, or clinical assessment. Investigators defined TTC as the number of months from the start of treatment to chemotherapy, death from any cause, last visit, or the end of study, whichever came first. The current standard of care treatment for this group of patients includes first line therapy with a CDK4/6 inhibitor plus an aromatase inhibitor.