Journal Article

Concordance of real-world versus conventional progression-free survival from a phase 3 trial of endocrine therapy as first-line treatment for metastatic breast cancer

Huang, Xin, Mardekian, Jack, Zhang, Zhe, Cotter, Matthew James, Parrinello, Christina M., Bourla, Ariel Bulua, Huang Bartlett, Cynthia

2020

Overview

There is growing interest in leveraging real-world data to complement knowledge gained from randomized clinical trials and inform the design of prospective randomized studies in oncology. The present study compared clinical outcomes in women with metastatic breast cancer who received letrozole as first-line monotherapy in oncology practices across the United States versus patients in the letrozole-alone cohort of the PALOMA-2 phase 3 trial. The real-world cohort (N = 107) was derived from de-identified patient data from the Flatiron Health electronic health record database. The clinical trial cohort (N = 222) comprised postmenopausal women in the letrozole-alone arm of PALOMA-2. Patients in the real-world cohort received letrozole monotherapy per labeling and clinical judgment; patients in PALOMA-2 received letrozole 2.5 mg/d, continuous. Real-world survival and response rates were based on evidence of disease burden curated from clinician notes, radiologic reports, and pathology reports available in the electronic health record. Progression-free survival and objective response rate in PALOMA-2 were based on Response Evaluation Criteria in Solid Tumors v1.1. Concordance of survival and response rates were retrospectively assessed using inverse probability of treatment weighting-adjusted Cox regression analysis. Inverse probability of treatment weighting-adjusted Cox regression results showed similar median progression-free survival in the real-world and PALOMA-2 cohorts (18.4 and 16.6 months, respectively): the hazard ratio using real-world data as reference was 1.04 (95% CI, 0.69-1.56). No significant difference was observed in response rates: 41.8% in the real-world cohort vs 39.4% in the PALOMA-2 cohort (odds ratio using real-world data as reference: 0.91 [95% CI, 0.57-1.44]). These findings indicate that data abstracted from electronic health records with proper quality controls can yield meaningful information on clinical outcomes. These data increase confidence in the use of real-world assessments of progression and response as efficacy endpoints. Trial registration NCT01740427; Funding: Pfizer.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Antineoplastic Agents, Hormonal - therapeutic use / Aromatase Inhibitors - therapeutic use / Breast cancer / Breast Neoplasms - drug therapy / Breast Neoplasms - mortality / Breast Neoplasms - pathology / Cancer / Care and treatment / Clinical medicine / Clinical trials / Comparative analysis / Cyclin-dependent kinases / Datasets / Disease / Drug therapy / Electronic health records / Electronic Health Records - statistics & numerical data / Electronic medical records / Electronic records / Endocrine therapy / Epidermal growth factor / Female / Health services / Humans / Letrozole - therapeutic use / Medical diagnosis / Medical records / Medical research / Medicine and Health Sciences / Metastases / Metastasis / Oncology / Oncology, Experimental / Patient outcomes / Patients / Pharmaceutical industry / Post-menopause / Postmenopausal women / Product development / Progression-Free Survival / Randomization / Receptor, ErbB-2 - metabolism / Receptors, Estrogen - metabolism / Receptors, Progesterone - metabolism / Regression analysis / Research and Analysis Methods / Response Evaluation Criteria in Solid Tumors / Solid tumors / Statistical analysis / Survival / Tumors / United States - epidemiology / Weighting / Womens health