ESMO Virtual Congress 2020: Darolutamide, Enzalutamide and Apalutamide the Risk of Adverse Events in Patients with Nonmetastatic Castration-Resistant Prostate Cancer: Number Needed to Harm

( Though patients with non-metastatic castration-resistant prostate cancer (nmCRPC) are generally asymptomatic from their cancer, the development of metastatic disease reduces their quality of life for several reasons. Three drugs that target the androgen receptor are approved in nmCRPC and delay time to the development of metastatic disease. However, treatment with these agents is associated with side effects that also reduce quality of life.

To contextualize the harm to patients from treatment for nmCRPC, Dr. Daniel George and colleagues calculated the number needed to harm for darolutamide, enzalutamide and apalutamide when used for the treatment of high-risk nmCRPC. The number needed to harm (NNH) reflects the baseline risk of adverse event (control), change in risk of the adverse event (experimental arm), and estimates the number of patients needed to receive treatment before a harmful outcome is expected to occur from the treatment. As an example, an NNH of 10 indicates that for every 10 patients treated over the course of the study, 1 additional adverse event is expected. For this study, all adverse events occurring in more than 5% of patients from the ARAMIS, SPARTAN, and PROSPER trials were included. The NNH was calculated by the inverse of the absolute change in risk of the adverse event studied over the course of the trial.

The NNH statistics are shown below. A negative NNH indicates a higher risk of the adverse event in the control arm, but in this study was conservatively interpreted as no additional risk. Numerically favorable NNH data was seen from the ARAMIS study of darolutamide across many adverse events. 


These statistics were then extrapolated to 4,318 high-risk nmCRPC patients (the number of patients within this clinical context expected based on epidemiological information in Europe) to generate estimates of how many patients would experience different adverse events.


By this metric, darolutamide would be expected to have the lowest number of adverse events.

The authors conclude that NNH metrics may help patients and decision-makers understand the risk of adverse events from treatment. Though darolutamide had the most favorable NNH profile amongst the three agents studied, the ability to draw firm conclusions is limited by differences in patient inclusion/exclusion and baseline characteristics between the trials.

Presented by: Daniel J. George, Medical Oncologist and Professor of Medicine, Duke University Medical Center, Durham, NC

Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, at the 2020 European Society for Medical Oncology Virtual Congress (#ESMO20), September 19th-September 21st, 2020