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Published on: March 6, 2018
Evaluating safety: Number needed to harm analyses of androgen receptor inhibitors in advanced prostate cancer
Daniel J George1, Karim Fizazi2, Alicia K Morgans3
1Duke Cancer Center, Duke University, Durham, NC, United States.
Introduction:
Androgen receptor inhibitors (ARIs) are standard of care in prostate cancer. Patient-centered treatment goals include optimizing efficacy, safety, tolerability, and quality of life, and prolonging time to treatment change. Number needed to harm (NNH) analyses can help contextualize adverse event (AE) risk and support treatment decisions. This exploratory study assessed NNH for AEs of interest with ARIs in nonmetastatic castration-resistant prostate cancer (nmCRPC) and metastatic hormone-sensitive prostate cancer (mHSPC).
Methods:
NNH was calculated using AE data from pivotal trials comparing ARIs plus androgen deprivation therapy (ADT) versus ADT and derived using the reciprocal of the absolute risk increase, then compared between ARIs.
Results:
In nmCRPC, darolutamide had a higher NNH (lower risk) than apalutamide and enzalutamide for the all-grade AEs hot flash (100.0/not reported [NR])/20.0), fatigue (29.4/10.8/5.3), arthralgia (negative [NEG]/11.9/100.0), cognitive impairment (≥ 250/47.6/33.3), hypertension (71.4/20.0/14.3), and falls (NEG/15.2/14.3) in the primary analysis, a trend generally maintained in the final analysis. A similar trend was reported for most grade ≥ 3 AEs. In mHSPC, darolutamide also had a higher NNH for most all-grade/grade ≥ 3 AEs. Exceptions included all-grade constipation (higher NNH for apalutamide and enzalutamide) and anemia (higher NNH for apalutamide). NNH comparisons across trials should be interpreted cautiously because of heterogeneity in trial designs and study populations.
Discussion:
Similar NNH trends observed in nmCRPC and mHSPC patient populations suggest a lower risk of incremental harm for most AEs with darolutamide versus apalutamide and enzalutamide. Understanding ARI risk profiles is key to optimizing treatment selection and improving tolerability in patients.
Insights
Androgen receptor inhibitors (ARIs) are used for prostate cancer. Darolutamide showed a lower risk of adverse events compared to apalutamide and enzalutamide in nonmetastatic castration-resistant and metastatic hormone-sensitive prostate cancer.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Androgen receptor inhibitors (ARIs) are standard treatments for prostate cancer.
- Optimizing treatment efficacy, safety, and quality of life is crucial for patients.
- Number Needed to Harm (NNH) analysis helps evaluate adverse event (AE) risks.
Purpose of the Study:
- To assess and compare the NNH for specific AEs associated with ARIs in prostate cancer.
- To evaluate the safety and tolerability profiles of different ARIs.
- To inform treatment selection for improved patient outcomes.
Main Methods:
- NNH was calculated using AE data from pivotal clinical trials.
- The study compared ARIs plus androgen deprivation therapy (ADT) against ADT alone.
- NNH was derived from the absolute risk increase and compared between ARIs.
Main Results:
- Darolutamide demonstrated a higher NNH (indicating lower risk) for most AEs compared to apalutamide and enzalutamide in both nmCRPC and mHSPC.
- This trend was observed for all-grade and severe (≥3) AEs, including fatigue, hot flashes, and cognitive impairment.
- Exceptions included constipation and anemia, where apalutamide and enzalutamide showed higher NNH values.
Conclusions:
- Darolutamide appears to have a lower incremental risk of harm for most AEs compared to apalutamide and enzalutamide.
- Understanding the AE profiles of ARIs is essential for optimizing treatment choices and enhancing patient tolerability.
- These findings support personalized treatment selection in prostate cancer management.
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