Breast cancer drugs: FDA approval, development time, efficacy, clinical benefits, innovation, trials, endpoints, quality of life, value, and price.

Autor: Michaeli JC; Department of Obstetrics and Gynaecology, LMU University Hospital, LMU Munich, Munich, Germany., Michaeli T; Department of Personalized Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, Germany.; DKFZ-Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany.; Division of Personalized Medical Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Trapani D; European Institute of Oncology, IRCCS, Milan, Italy.; Department of Oncology and Hematology, University of Milan, Milan, Italy., Albers S; Department of Orthopaedics and Sport Orthopaedics, School of Medicine, Klinikum Rechts Der Isar, Technical University of Munich, Munich, Germany., Dannehl D; Department of Women's Health, Tuebingen University Hospital, Tübingen, Germany., Würstlein R; Department of Obstetrics and Gynaecology, LMU University Hospital, LMU Munich, Munich, Germany., Michaeli DT; Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany. danielmichaeli@yahoo.com.
Jazyk: angličtina
Zdroj: Breast cancer (Tokyo, Japan) [Breast Cancer] 2024 Nov; Vol. 31 (6), pp. 1144-1155. Date of Electronic Publication: 2024 Sep 25.
DOI: 10.1007/s12282-024-01634-x
Abstrakt: Objective: This study analyzes the development, benefits, trial evidence, and price of new breast cancer drugs with US Food and Drug Administration (FDA) approval.
Methods: We identified 26 drugs with 42 FDA-approved indications for early and metastatic breast cancer (2000-2023). Data were collected from FDA labels, clinicaltrials.gov, and Medicare and Medicaid. Overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) and tumor response's relative risk (RR) alongside objective response rate (ORR) were meta-analyzed.
Results: The median development time for breast cancer drugs was 7.8 years (95% CI 6.2-10.8). 26% of treatments were considered innovative ("first-in-indication") with 88% acting via a targeted mechanism. 64% were small molecules, 19% antibodies, and 18% antibody-drug conjugates. 38% were approved for HR + and 31% for HER2 + breast cancer. 6 indications were for early and 36 for metastatic breast cancer. Indications utilized FDA's special programs: orphan (2%), fast track (24%), accelerated approval (19%), priority review (74%), breakthrough therapy (44%). Approval was predominantly supported by phase 3 trials (88%) of randomized controlled design (66%), enrolling a median of 585 patients (IQR 417-752) at 181 centers (IQR 142-223) across 19 countries (IQR 17-20). New drugs' HR were 0.78 for OS (95% CI 0.74-0.82) and 0.59 for PFS (95% CI 0.54-0.64) with a RR for tumor response of 1.61 (95% CI 1.46-1.76). Median improvements of OS were 2.8 months (IQR 1.8-5.8) and PFS were 4.4 months (IQR 2.2-7.1). In single-arm trials, the average ORR was 31% (95% CI 10-53). In meta-regressions, the correlation between OS/PFS was 0.34 (p = 0.031) and OS/response was 0.01 (p = 0.435). 60% of treatments had a 'high-value' ESMO-MCBS score with 14% demonstrating improvements in quality of life. The median price was $16,013 per month (95% CI 13,097-17,617). There was no association between prices and patient benefit. The median value per life year gained was $62,419 (IQR 25,840-86,062).
Conclusions: Over the past two decades, the development of innovative and effective drugs transformed the treatment landscape for breast cancer patients. Yet, investigators and regulators must safeguard that highly-priced new drugs demonstrate improvements in patient-centered clinical endpoints: overall survival and quality of life.
(© 2024. The Author(s).)
Databáze: MEDLINE
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