Real-world study of overall survival with palbociclib plus aromatase inhibitor in HR+/HER2− metastatic breast cancer

Abstract

Data on real-world effectiveness of cyclin-dependent kinase 4/6 inhibitor combination therapy versus endocrine therapy alone are limited. The Flatiron Health Analytic Database was used to assess overall survival (OS) in patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2−) metastatic breast cancer (MBC) treated with first-line palbociclib plus an aromatase inhibitor (AI) versus an AI alone in routine US clinical practice. In total, 2888 patients initiated treatment during February 3, 2015–March 31, 2020, with a potential ≥6-month follow-up (cutoff date, September 30, 2020). After stabilized inverse probability treatment weighting, median OS (95% CI) is significantly longer among palbociclib versus AI recipients (49.1 [45.2–57.7] versus 43.2 [37.6–48.0] months; hazard ratio, 0.76 [95% CI, 0.65–0.87]; P < 0.0001). Progression-free survival (95% CI) is 19.3 (17.5–20.7) versus 13.9 (12.5–15.2) months, respectively (hazard ratio, 0.70 [95% CI, 0.62–0.78]; P < 0.0001). These data support first-line palbociclib plus an AI treatment for HR+/HER2− MBC.(Trial number NCT05361655).

HR+/HER2– de novo metastatic breast cancer: a true peculiar entity?

“…Additionally, in routine practice, the proportion of patients with dnMBC is much higher than that reported in epidemiological reports, with the number reaching up to 40% of the population observed. [72][73][74][75][76][77][78][79] One of the largest real-world studies derives data from the Flatiron's health longitudinal database, which includes de-identified electronic health records from more than 280 cancer clinics and represents 2.4 million patients with cancer treated in the USA. 72 This retrospective observational study included 1430 patients receiving first-line treatment with palbociclib and letrozole or letrozole alone for MBC from 2015 to 2019.…”

“…72 A larger study using the same database and including 2,880 patients treated for their MBC with palbociclib and a NSAI from 2015 to 2020 has been recently published (P-REALITY X). 73 A significant OS benefit for the palbociclib combinations versus the NSAI arm consistent with both statistical methods used (49.1 versus 43.2 months, HR 0.76, 96% CI 0.65-0.87; p<0.000, with the stabilized inverse probability treatment weighting analysis, and 57.8 months versus 43.5 months, HR 0.72, 95% CI 0.62-0.83; p<0.0001, with propensity score matching analysis) was confirmed. 74 As for dnMBC, the significant benefit of the addition of palbociclib was confirmed and was similar to that of patients with disease recurring after >5 years.…”

“…74 As for dnMBC, the significant benefit of the addition of palbociclib was confirmed and was similar to that of patients with disease recurring after >5 years. 73 The Ibrance Real world Insights Study (IRIS) is a worldwide retrospective study based on medical chart review of patients who received palbociclib in combination with an aromatase inhibitor (AI) or with fulvestrant. [74][75][76] The European cohort included 1723 patients, with 761 (44% of the total population) having dnMBC 88% of whom were treated with an AI and 12% with fulvestrant.…”

Palbociclib Adherence and Persistence in Patients with Hormone Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) Metastatic Breast Cancer

“…One plausible explanation is that bone-only metastasis in mBC patients has a relatively good prognosis versus patients with other metastasis such as visceral diseases. 6 , 13 , 31 After disease progression is controlled, palbociclib may likely be switched to endocrine therapy (ET) only because palbociclib in combination with ET is costly and may cause additional adverse reactions such as neutropenia.…”

The dilemma of selecting a first line CDK4/6 inhibitor for hormone receptor-positive/HER2-negative metastatic breast cancer

“…Of note, 10% of patients on the study arm continue on palbociclib, at 7.5 years of follow-up. In comparison to the PALOMA-2 report, real-world data analyses of U.S.-based outcomes for patients receiving first-line endocrine based therapy have reported PFS and OS benefits for the combination of palbociclib and letrozole over letrozole alone, with an observed improvement in median PFS from 11.9 months to 20.0 months (HR 0.58; 95% CI 0.49–0.69; P < 0.0001), and median OS from 40.4 to 53.4 months (HR 0.67; 95% CI, 0.60–0.76; P < 0.0001) 27 , 28 . As for abemaciclib in the first-line setting, in a pre-specified interim survival analysis of the MONARCH-3 trial at a median follow up of 70.2 months, the addition of abemaciclib to NSAI demonstrated a median OS of 67.1 months compared to 54.5 months for placebo plus NSAI (HR = 0.754, 95% CI, 0.584–0.974, two-sided P = 0.0301) 29 .…”