Overall Survival and the Evolving Benefit-Risk Assessment for Poly (ADP-ribose) Polymerase Inhibitors in Advanced Ovarian Cancer
Abstract
From 2014 through 2019, the US Food and Drug Administration (FDA) granted approval to six indications for poly (ADP-ribose) polymerase (PARP) inhibitors in advanced epithelial ovarian cancer (EOC). From 2022 through 2023, these six indications were withdrawn or narrowed after observation of a potential detrimental effect on overall survival (OS) in four randomized controlled trials. The indications for niraparib, olaparib, and rucaparib for the treatment of BRCA -mutated or homologous recombination deficiency–positive advanced EOC were withdrawn. The indications for niraparib, olaparib, and rucaparib for the maintenance treatment of recurrent EOC were narrowed to only patients with BRCA mutations. Recognizing the clinical implications of these regulatory actions, herein we describe the FDA's decision-making process and the rationale behind the removal or narrowing of these indications for PARP inhibitors in advanced EOC. Furthermore, this article provides insight into the FDA's interpretation of potential OS detriments and subgroup analyses to shape regulatory decisions.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (17)
Mirat Shah
Office of Oncologic Diseases, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD
Ting-Yu Chen
Gwynn Ison
Mirat Shah, MD, Mallorie H. Fiero, PhD, Joyce Cheng, PhD, Ting-Yu Chen, PhD, and Gwynn Ison, MD, Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, Silver Spring, MD; Richard Pazdur, MD, and Laleh Amiri-Kordestani, MD, Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, Silver Spring, MD, Oncology Center of Excellence (OCE), US Food and Drug Administration, Silver Spring, MD
Mallorie H. Fiero
Office of Biostatistics, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD
Hui Zhang
The Fourth Hospital of Hebei Medical University Shijiazhuang China
Xin Gao
Marc Neilson
Oncology Center of Excellence (OCE), U.S. Food and Drug Administration, Silver Spring, MD
Kirsten B. Goldberg
Oncology Center of Excellence (OCE), U.S. Food and Drug Administration, Silver Spring, MD
Abhilasha Nair
United States Food and Drug Administration - Center for Drug Evaluation and Research, Office of New Drugs, Office of Oncologic Diseases, Silver Spring, MD
Tiffany K. Ricks
US Food and Drug Administration, Silver Spring, MD
William F. Pierce
US Food and Drug Administration, Silver Spring, MD
Nicole Gormley
US Food and Drug Administration, Silver Spring, MD
Marc R. Theoret
Shenghui Tang
US Food and Drug Administration, Silver Spring, MD
Richard Pazdur
From the Oncology Center of Excellence (G.U.M., R.P.) and the Office of the Commissioner (N.N.B., R.M.C.), Food and Drug Administration, Silver Spring, MD.
Paul G. Kluetz
Laleh Amiri-Kordestani