Frontline Palbociclib Combo Improves Outcomes in Real-World HR+/HER2-Negative Breast Cancer Population From Disadvantaged Areas

Findings from a real-world analysis demonstrated that first-line treatment with the combination of palbociclib (Ibrance) and an aromatase inhibitor (AI) was associated with prolonged overall survival (OS) and progression-free survival (PFS) compared with an AI alone in patients with hormone receptor–positive, HER2-negative metastatic breast cancer living in disadvantaged neighborhoods in the United States.

Findings from the real-world analysis at the 42nd Annual Miami Breast Cancer Conference®, an event held by Physicians’ Education Resource, LCC, showed that in an unadjusted analysis, patients from disadvantaged neighborhoods who received palbociclib plus an AI (n = 394) achieved a median OS of 57.2 months (95% CI, 49.6-70.8) compared with 37.7 months (95% CI, 28.7-44.8) for patients treated with an AI alone (n = 329; HR, 0.64; 95% CI, 0.52-0.80; P < .0001). Additionally, results from a stabilized inverse probability of treatment weighting (sIPTW) analysis, which was the study’s primary analysis, revealed that the median OS was 57.1 months (95% CI, 47.2-70.8) for palbociclib plus an AI (n = 405) compared with 38.2 months (95% CI, 29.6-48.0) for an AI alone (n = 324; HR, 0.70; 95% CI, 0.55-0.90; P = .0053). The median follow-up duration was 27.2 months vs 25.7 months in patients treated with palbociclib/AI and AI alone, respectively.

“Generating more equitable outcomes for patients with metastatic breast cancer in vulnerable populations such as those residing in low-income areas is a crucial public health objective, but data on the effectiveness of CDK 4/6 inhibitors/endocrine therapy combinations in patients with metastatic breast cancer with low socioeconomic status [SES] are lacking,” lead author Filipa Lynce, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and coauthors wrote in a poster presentation of the analysis. “The current study aimed to understand the real-world effectiveness of first-line palbociclib plus an AI vs an AI alone in patients with hormone receptor–positive, HER2-negative metastatic breast cancer living in disadvantaged neighborhoods.”

Study Design and Patient Characteristics

The retrospective, observational study included patient data gathered from the United States nationwide Flatiron Health metastatic breast cancer electronic health records-derived deidentified database. Investigators identified patients with hormone receptor–positive, HER2-negative metastatic breast cancer and were randomly sampled (n = 5500); patients needed to be at least 18 years of age, and they needed to start first-line treatment between February 2015 and June 2022. Among these patients, 5087 had first-line treatment data manually confirmed via abstraction, of which 1342 were treated with first-line palbociclib/AI and 1108 were treated with first-line AI alone.

Of the patients treated with palbociclib/AI, 29.4% met the criteria for living in disadvantaged neighborhoods; 29.7% of patients treated with AI alone met the respective criteria.

The main objective of the analysis was to compare OS and real-world PFS of first-line palbociclib/AI vs AI alone in patients with hormone receptor–positive, HER2-negative metastatic breast cancer living in disadvantaged neighborhoods in the United States.

In the sIPTW analysis population, the median age at diagnosis of metastatic disease was 69 years and 68 years in patients treated with palbociclib/AI (n = 405) and AI alone (n = 324), respectively, and the majority of patients were female (palbociclib/AI, 98.9%; AI alone, 98.7%). Patients were White (56.8%; 58.6%), Black (17.2%; 17.5%), or other (26.0%; 23.9%). The majority were treated in a community practice (84.2%; 83.6%), and some were treated in an academic setting (15.8%; 16.4%). Disease stage at diagnosis included stage I (15.0%; 13.3%), stage II (28.8%; 28.2%), stage III (16.1%; 18.0%), stage IV (31.4%; 31.0%), or undocumented (8.7%; 9.6%).

Of note, de novo disease was observed in 31.4% and 31.0% of patients treated with palbociclib/AI and AI alone, respectively. Patients mostly did not have visceral metastases (palbociclib/AI, 74.6%; AI alone, 75.7%), and mostly had an ECOG performance status of 0 (29.1%; 29.6%).

Based on the primary analysis, subsequent treatments included CDK4/6 inhibitor (palbociclib/AI, 47.4%; AI alone, 72.8%), chemotherapy (8.6%; 8.9%), endocrine therapy alone (9.2%; 23.5%), and other anticancer treatment (11.4%; 3.4%).

Additional Efficacy Data

Median real-world PFS was shown to be significantly longer in the palbociclib/AI group compared with the AI alone group in both the unadjusted and sIPTW analyses. Specifically in the unadjusted analysis, median real-world PFS was 21.8 months (95% CI, 18.8-28.0) vs 13.5 months (95% CI, 11.2-19.3) in the palbociclib/AI and AI alone groups, respectively (HR, 0.59; 95% CI, 0.48-0.73; P < .0001). In the sIPTW analysis, the median real-world PFS was 19.1 months (95% CI, 15.8-24.2) vs 14.0 months (95% CI, 10.7-19.7) in the respective groups (HR, 0.66; 95% CI, 0.52-0.84; P = .0007).

Similarly, the median time to second progression (PFS2) was significantly prolonged in the palbociclib/AI vs AI alone groups in both the unadjusted and sIPTW analyses. In the unadjusted analysis, the median PFS2 was 36.9 months (95% CI, 31.1-44.1) vs 21.1 months (95% CI, 15.4-23.4) in the palbociclib/AI vs AI alone groups, respectively (HR, 0.51; 95% CI, 0.42-0.63; P < .0001). Median PFS2 reported in the sIPTW analysis was 32.7 months (95% CI, 27.8-41.0) vs 22.5 months (95% CI, 16.9-27.3) in the respective groups (HR, 0.62; 95% CI, 0.49-0.79; P = .0001).

Investigators noted that the study was limited by its retrospective, observational design. Other limitations noted included potential incomplete, missing, or inaccurate database entries; lack of random assignment for treatment; lack of a predefined schedule to assess disease progression; the effect of potential cofounders that could not be adjusted for in the sIPTW analysis; and limitation of the data to patients treated in the United States.

Reference

Lynce F, Liu X, Li B, et al. Real-world effectiveness of palbociclib plus an aromatase inhibitor in HR+/HER2– MBC patients living in disadvantaged neighborhoods. Presented at: 42nd Annual Miami Breast Cancer Conference. March 6-9, 2025; Miami Beach, FL. Abstract 44.