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P-VERIFY: The Largest Real-World Comparative Overall Survival Analysis of First-line CDK4/6 Inhibitors + AI in HR+/HER2- mBC to Date

STUDY OBJECTIVE

To compare OS of patients with HR+/HER2- mBC receiving first-line palbociclib, ribociclib or abemaciclib in combination with an Al in US clinical practice.*1

STUDY DESIGN

  • The Flatiron Health database is a comprehensive dataset with broad and timely access to data from 700,000+ patients with breast cancer.1
  • This nationwide database was curated using natural language processing with machine learning and technology-enabled abstraction.1
  • The data model characterises the entire journey of a patient with breast cancer, from early to metastatic disease, with treatment details, clinical characteristics and validated real-world outcomes.1
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*Patients still alive were censored at the end of the study.1 †Unadjusted analyses were conducted first, followed by sIPTW for the primary analysis. sIPTW is a statistical technique used in real-world studies to adjust for key baseline variables;2. While sIPTW and multivariable analyses were used to balance baseline characteristics, unmeasured confounders cannot be addressed through these methods. Sensitivity analyses included multivariable analyses, 1:1 exact matching and a sub-analysis for patients who started index treatment in 2017 or later;1 ‡Patients were followed from start of index treatment to data cut-off, death or last medical activity, whichever came first.1

PATIENT CHARACTERISTICS

*Except for insurance type;†Multiple metastases at the same site were counted as one site (e.g., three bone metastases in the spine were considered only one site);1 ‡Visceral disease is defined as metastatic disease in the lung and/or liver; patients could have had other sites of metastases;§Bone-only disease is defined as metastatic disease in the bone only.1

RESULTS

*OS was a secondary endpoint in all three pivotal first-line CDK4/6 inhibitor RCTs in HR+/HER2- mBC. Palbociclib + letrozole did not show a statistically significant OS difference in PALOMA-2.1,6 Abemaciclib + AI did not show statistically significant OS difference in MONARCH-3.7 Ribociclib + letrozole demonstrated a statistically significant OS difference in MONALEESA-2;†OS was defined as the number of months from start of index treatment to death. Patients still alive were censored at the study cut-off date (31 May 2024);1 ‡Median duration of follow-up in the palbociclib, ribociclib and abemaciclib groups was 33 months, 15.7 months and 21.5 months, respectively, with 45.3%, 25.6% and 28% of deaths observed, respectively.1

CONCLUSIONS
  • P-VERIFY (Palbociclib Verifying Evidence of Real-world Impact Study) is a comparative OS analysis of first-line palbociclib, ribociclib and abemaciclib plus an Al for HR+/HER2- mBC in routine US clinical practice from the Flatiron Health database.1
  • Although further confirmatory research is needed, the findings of P-VERIFY suggest that there are no significant differences in OS outcomes between first-line palbociclib, ribociclib, or abemaciclib used in combination with an Al for HR+/HER2- mBC patients in clinical practice in the US.1

P-VERIFY, palbociclib verifying evidence of real world impact study; Al, aromatase inhibitor; CDK4/6, cyclin-dependent kinase 4/6; Cl, confidence interval; HER2-, human epidermal growth factor receptor 2 negative; HR+, hormone receptor positive; mBC, metastatic breast cancer; OS, overall survival; slPTW, stabilised inverse probability treatment weighting; ECOG PS, Eastern Cooperative Oncology Group performance status; OS, overall survival; RCT, randomised controlled trial

References

Rugo HS, et al. ESMO Open 2025; 10(1):104103. Xu S, et al. Value Health 2010;13(2):273-277.IBRANCE® (palbociclib) Summary of Product Characteristics for United KingdomRibociclib Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/product/8110/smpc Abemaciclib Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/product/9532/smpc Slamon DJ, et al. J Clin Oncol 2024;42(9):994–1000.Goetz MP, et al. Ann Oncol 2024;35(8):718–727. Hortobagyi GN, et al. N Engl J Med 2022;386(10):942–950.
PP-IBR-GBR-6964. April 2026

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