631P - Darolutamide (D), enzalutamide (E) and apalutamide (A), the risk of adverse events (AEs) in patients with non-metastatic castration-resistant prostate cancer (nmCRPC): Number needed to harm (NNH)

Background

Patients with nmCRPC are typically asymptomatic but at risk of metastases, leading to reduced quality of life. Three androgen receptor inhibitors (D, E, A) investigated for the treatment of nmCRPC offer clinical benefits but also increased risk of AEs. Contextualizing risks of AEs, or harm, to patients can be challenging. NNH measures the number of patients who need to receive treatment before a harmful outcome occurs with the intervention, compared to the control. Thus, a higher NNH reflects a lower incremental likelihood of harm.

Methods

MEDLINE and EMBASE were searched for relevant clinical trials (CTs). AEs occurring in ≥5% of either CT arm were extracted from the PROSPER (E), SPARTAN (A) and ARAMIS (D) publications. NNH by AE (by grade 1-2, ≥3) were calculated over the duration of each CT based on reported rates, using the inverse of the absolute risk increase (1 / experimental AE rate - control AE rate). An exploratory analysis considered the application of results to a European (EU) population (assuming trial-based AE rates to be representative of real-world rates).

Results

NNH were higher across the class for grade ≥3 AEs (min: NNH 40), grade 1-2 (min: NNH 6). Results (see Table) show a trend of higher NNH for AEs in ARAMIS across grade 1-2 and grade ≥3 AEs indicating a lower likelihood of incremental harm for fatigue, falls, dizziness and hypertension for D versus A and E. Table: 631P

NR: Not reported, Negative NNH = higher risk in control

Selecting treatment with the highest NNH (versus lowest) for an estimated 4,300 EU high risk nmCRPC patients could translate to AE reductions (events) for fatigue (645), falls (311) and hypertension (233) over the duration of the CTs (18-20 months).

Conclusions

NNH can help contextualize the risk of AEs. Findings show a consistent trend of higher NNH for D compared to A and E, and that AE profile may be noteworthy for healthcare systems as well as patients. Prospective comparative trials are needed to further confirm these findings.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Bayer Healthcare Pharmaceuticals.

Funding

Bayer Healthcare Pharmaceuticals.

Disclosure

D.J. George: Research grant/Funding (self): Acerta Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (self): Astellas ; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy: Axess Oncology ; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Bayer Healthcare Pharamceutcials; Research grant/Funding (self): Calithera; Honoraria (self): EMD Serono ; Advisory/Consultancy: Flatiron; Honoraria (self): Ipsen; Advisory/Consultancy: Merck Sharp & Dohme ; Honoraria (self), Advisory/Consultancy: Michael J Hennessey Associates ; Advisory/Consultancy: Myovant Sciences, Inc ; Research grant/Funding (self): Novartis; Advisory/Consultancy: Nektar Therapeutics ; Advisory/Consultancy: Physician Education Resource LLC ; Advisory/Consultancy: Vizuri Health Sciences, LLC ; Honoraria (self): UroGPO ; Honoraria (self), Travel/Accommodation/Expenses: UroToday; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Sanofi; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Pfizer; Advisory/Consultancy: Modra Pharmaceuticals B.V. ; Advisory/Consultancy: Capio Biosciences ; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Exelixis, Inc ; Advisory/Consultancy, Research grant/Funding (self): Janssen Pharmaceuticals ; Advisory/Consultancy: Leidos Biomedical Research Inc; Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb. A.R. Waldeck: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bayer Healthcare Pharmaceuticals. H. Guo: Full/Part-time employment: Bayer Healthcare Pharmaceuticals. A.J. Upton: Full/Part-time employment: Bayer Healthcare.