Palbociclib plus endocrine therapy significantly enhances overall survival of HR+/HER2− metastatic breast cancer patients compared to endocrine therapy alone in the second‐line setting: A large institutional study

Abstract

Cyclin‐dependent‐kinase‐4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET) is standard of care for patients with advanced hormone receptor (HR)‐positive, HER2‐negative breast cancer (BC). The Breast Medical Oncology database at MD Anderson Cancer Center (MDACC) was analyzed to assess effectiveness of the CDK4/6i palbociclib plus ET compared to ET alone. From a total of 5402 advanced HR+ HER2− BC patients referred to MDACC between 1997 and 2020, we identified eligible patients who received palbociclib in combination with first‐line (n = 778) and second‐line (n = 410) ET. We further identified “control” patients who received ET alone in the first‐line (n = 2452) and second‐line (n = 1183) settings. Propensity score matching analysis was conducted to balance baseline demographic and clinical characteristics between palbociclib and control cohorts to assess the effect of palbociclib treatment on progression‐free survival (PFS) and overall survival (OS). For propensity‐matched‐cohort in the first‐line setting (n = 708), palbociclib group had significantly longer median PFS (17.4 vs 11.1 months; P < .0001) compared to controls. Median OS (44.3 vs 40.2 months) did not show a statistically significant benefit in the first line setting. However, in the second‐line setting, with 380 propensity‐matched‐cohort, the palbociclib group had significantly longer PFS (10 vs 5 months, P < .0001) as well as OS (33 vs 24 months; P < .022), compared to controls. We conclude that in this single center analysis of a large cohort of metastatic HR+ HER2− BC patients, palbociclib in combination with ET was associated with improved PFS in both first‐line and second‐line settings and OS in the second‐line setting compared to ET alone cohort.

Histology-based survival outcomes in hormone receptor-positive metastatic breast cancer treated with targeted therapies

“…Our study reported a mPFS between 16.0 months (in IDC) and 18.8 months (in ILC) with patients treated with CDK4/6is + AI which is lower than that reported in the PALOMA-1 (20.2 months) 27 and PALOMA-2 (24.8 months) 28 trials. This discrepancy is consistent with other reported real-world data of palbociclib in combination with ET that showed similar shorter mPFS metrics when compared with more homogeneous prospective phase 3 clinical trial data 29,30 . One of the reasons for this discrepancy may be that the PALOMA-1 and -2 trials had patients from countries with much less pretreatment (i.e., more de novo cases and less prior exposure to chemotherapy and ET) compared to our population.…”

“…The median PFS and OS durations reported here were consistent with those from previous studies performed using data from the same database 29 . The mPFS and mOS durations observed with 1L CDK4/6is plus FUL (Fig.…”

Overall survival associated with CDK4/6 inhibitors in patients with HR+/HER2– metastatic breast cancer in the United States: A SEER‐Medicare population‐based study

“…In an observational study of a relatively younger population of patients (median age, 67 years for exposure group) in a US electronic health records database, the relative rate of OS with first‐line letrozole/palbociclib combination was significantly longer compared with letrozole alone (HR, 0.66 [95% CI, 0.53–0.82]) 7 . In another observational study representing younger patients (median age, 51 years for exposure group) from a single institution, palbociclib/aromatase inhibitor combination versus aromatase inhibitor alone did not show OS benefits in the first line, but in the second‐line setting, it was associated with a significant lower rate of all‐cause mortality (HR, 0.67 [95% CI, 0.52–0.87]) 9 . In our current analysis of older Medicare patients, the adjusted HR estimates from multivariable analyses (0.598 [95% CI, 0.428–0.834] for the first‐line setting; 0.422 [95% CI, 0.243–0.733] for second‐line setting) suggest meaningful OS benefits with CDK4/6 inhibitors, supplementing the existing data obtained from the pivotal trials and observational studies.…”

“…7,8 In another study, Ha and colleagues (2022) documented evidence of OS benefits with palbociclib from a single cancer center. 9 However, evidence from these observational studies lack generalizability in an older population of patients, such as those covered in the US Medicare system, considering the differences in population characteristics. In the older Medicare population with cancer, survival outcomes associated with novel oncology treatments have been shown to differ substantially when compared with patients represented in clinical trial, 10 further highlighting the importance of assessing these outcomes from the perspective of Medicare, which provides health care coverage to more than 55 million individuals aged 65 years and older in the United States.…”

“…In two retrospective analyses of electronic health records, overall survival (OS) rates in women with HR+ MBC who were treated with palbociclib/letrozole were compared with women treated with letrozole alone 7,8 . In another study, Ha and colleagues (2022) documented evidence of OS benefits with palbociclib from a single cancer center 9 . However, evidence from these observational studies lack generalizability in an older population of patients, such as those covered in the US Medicare system, considering the differences in population characteristics.…”