Minh-Phuong Huynh-Le1, Randall C Shults1, Michael J Connor1, Jona A Hattangadi-Gluth2. 1. Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA. 2. Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA. Electronic address: jhattangadi@ucsd.edu.
Abstract
BACKGROUND: Radionuclide radium-223 improves survival in men with metastatic castrate-resistant prostate cancer. The United States (US) Food and Drug Administration Adverse Events Reporting System (FAERS) is a post-market pharmacovigilance database valuable for adverse event (AE) assessments. We analyzed FAERS to identify disproportionate AE signals related to radium-223, and to explore radium-223's international utilization. MATERIALS AND METHODS: We identified 2182 radium-223 cases associated with AE(s) from 2013 to 2018. The duration of radium-223 therapy was calculated. Reporting odds ratio (ROR) and proportional reporting ratio (PRR), with 95% confidence intervals (CIs), were calculated for AEs of interest. ROR shows disproportionate signals if the lower limit of the 95% CI > 1. PRR shows disproportionate signals if PRR ≥ 2, χ2 statistic ≥ 4, and ≥ 3 AEs were reported. We identified any US Food and Drug Administration enforcement actions for radium-223. RESULTS: A majority (60.8%) of events occurred outside the US. Among patients with radium-223-associated AEs, the median therapy duration was only 56 days (corresponding to 2-3 treatment cycles). Disproportionate signals were detected for general health deterioration (ROR, 5.03; 95% CI, 4.23-5.98 and PRR, 4.94; 95% CI, 4.16-5.87), bone pain (ROR, 4.53; 95% CI, 3.67-5.59 and PRR, 4.48; 95% CI, 3.63-5.53), and hematologic AEs including anemia (ROR, 2.89; 95% CI, 2.55-3.27 and PRR, 2.80; 95% CI, 2.48-3.17), thrombocytopenia (ROR, 3.22; 95% CI, 2.77-3.74 and PRR, 3.16; 95% CI, 2.72-3.67), and pancytopenia/bone marrow failure (ROR, 4.83; 95% CI, 4.11-5.67 and PRR, 4.73; 95% CI, 4.03-5.55). There were no enforcement actions for radium-223. CONCLUSIONS: Patients with metastatic castrate-resistant prostate cancer experiencing AEs are only receiving one-half the prescription dose of radium-223 required for survival benefit. Radium-223 is associated with health deterioration, bone pain, and hematologic AEs. Real-world analyses are important for ongoing radium-223 risk-benefit assessments.
BACKGROUND: Radionuclide radium-223 improves survival in men with metastatic castrate-resistant prostate cancer. The United States (US) Food and Drug Administration Adverse Events Reporting System (FAERS) is a post-market pharmacovigilance database valuable for adverse event (AE) assessments. We analyzed FAERS to identify disproportionate AE signals related to radium-223, and to explore radium-223's international utilization. MATERIALS AND METHODS: We identified 2182 radium-223 cases associated with AE(s) from 2013 to 2018. The duration of radium-223 therapy was calculated. Reporting odds ratio (ROR) and proportional reporting ratio (PRR), with 95% confidence intervals (CIs), were calculated for AEs of interest. ROR shows disproportionate signals if the lower limit of the 95% CI > 1. PRR shows disproportionate signals if PRR ≥ 2, χ2 statistic ≥ 4, and ≥ 3 AEs were reported. We identified any US Food and Drug Administration enforcement actions for radium-223. RESULTS: A majority (60.8%) of events occurred outside the US. Among patients with radium-223-associated AEs, the median therapy duration was only 56 days (corresponding to 2-3 treatment cycles). Disproportionate signals were detected for general health deterioration (ROR, 5.03; 95% CI, 4.23-5.98 and PRR, 4.94; 95% CI, 4.16-5.87), bone pain (ROR, 4.53; 95% CI, 3.67-5.59 and PRR, 4.48; 95% CI, 3.63-5.53), and hematologic AEs including anemia (ROR, 2.89; 95% CI, 2.55-3.27 and PRR, 2.80; 95% CI, 2.48-3.17), thrombocytopenia (ROR, 3.22; 95% CI, 2.77-3.74 and PRR, 3.16; 95% CI, 2.72-3.67), and pancytopenia/bone marrow failure (ROR, 4.83; 95% CI, 4.11-5.67 and PRR, 4.73; 95% CI, 4.03-5.55). There were no enforcement actions for radium-223. CONCLUSIONS:Patients with metastatic castrate-resistant prostate cancer experiencing AEs are only receiving one-half the prescription dose of radium-223 required for survival benefit. Radium-223 is associated with health deterioration, bone pain, and hematologic AEs. Real-world analyses are important for ongoing radium-223 risk-benefit assessments.
Authors: Mara A McAdams; Laura A Governale; Lynette Swartz; Tarek A Hammad; Gerald J Dal Pan Journal: Pharmacoepidemiol Drug Saf Date: 2008-09 Impact factor: 2.890
Authors: Michael J Connor; Deborah C Marshall; Vitali Moiseenko; Kevin Moore; Laura Cervino; Todd Atwood; Parag Sanghvi; Arno J Mundt; Todd Pawlicki; Abram Recht; Jona A Hattangadi-Gluth Journal: Int J Radiat Oncol Biol Phys Date: 2017-01-01 Impact factor: 7.038
Authors: Fred Saad; Joan Carles; Silke Gillessen; Axel Heidenreich; Daniel Heinrich; Jeremy Gratt; Jérémy Lévy; Kurt Miller; Sten Nilsson; Oana Petrenciuc; Marcello Tucci; Manfred Wirth; Judith Federhofer; Joe M O'Sullivan Journal: Lancet Oncol Date: 2016-07-26 Impact factor: 41.316
Authors: Benjamin L Maughan; Adam Kessel; Taylor Ryan McFarland; Nicolas Sayegh; Roberto Nussenzveig; Andrew W Hahn; John M Hoffman; Kathyrn Morton; Deepika Sirohi; Manish Kohli; Umang Swami; Kenneth Boucher; Benjamin Haaland; Neeraj Agarwal Journal: Oncologist Date: 2021-09-23