Comparative efficacy of apalutamide darolutamide and enzalutamide for treatment of non-metastatic castrate-resistant prostate cancer: A systematic review and network meta-analysis
Highlights
• Apalutamide, darolutamide and enzalutamide outcomes in nonmetastatic castrate-resistant prostate cancer patients were compared by network meta-analysis
• Wyniki leczenia apalutamidem, darolutamidem i enzalutamidem u pacjentów z rakiem prostaty opornym na kastrację bez przerzutów zostały porównane za pomocą metaanalizy sieciowej
• Enzalutamide and apalutamide had higher metastasis free survival rate than darolutamide.
• Enzalutamid i apalutamid miały wyższy wskaźnik przeżycia bez przerzutów niż darolutamid.
• As a class of drugs, second-generation androgen receptor antagonists improve overall survival in nonmetastatic castrate-resistant prostate cancer patients.
• Jako klasa leków, antagoniści receptora androgenowego drugiej generacji poprawiają całkowity czas przeżycia u pacjentów z rakiem prostaty bez przerzutów opornych na kastrację.
• All medications had comparable adverse event rates, although the probability is lower with Darolutamide.
• Wszystkie leki miały porównywalne wskaźniki zdarzeń niepożądanych, chociaż prawdopodobieństwo jest mniejsze w przypadku Darolutamidu.
Abstract
Introduction:
Studies using apalutamide, enzalutamide, or darolutamide have shown improved metastasis free survival (MFS) rates, leaving clinicians with a dilemma of choosing one over the other, for nonmetastatic castration recurrent prostate cancer (nmCRPC). We performed a network meta-analysis to provide an indirect comparison of oncologic outcomes and adverse events (AEs) of these medications.
Material and Methods:
We searched PubMed, MEDLINE, and SCOPUS databases, for studies reporting apalutamide, enzalutamide, or darolutamide until January 25, 2020. Results were input into an EndNote library, and data were extracted into a predefined template.
Progression free survival (PFS) was defined as radiologic progression or death. Network meta-analysis was done using R and meta-analysis was performed with RevMan v. 5.
Surface under the cumulative ranking (SUCRA) value was used to provide rank probabilities.
Results:
We found 3 studies reporting results for apalutamide, enzalutamide, and darolutamide.
MFS was significantly lower in patients receiving darolutamide compared to both apalutamide (hazard ratio
: 0.73, 95% confidence interval [CI]: 0.55–0.97) and enzalutamide (HR: 0.71, 95% CI: 0.54–0.93).
MFS was similar for enzalutamide and apalutamide (HR: 0.97, 95% CI: 0.73–1.28).
In PFS, apalutamide showed a slightly higher rate compared to darolutamide (HR: 0.76, 95% CI: 0.59–0.99).
There was no difference in overall survival (OS) between any of the medications.
There was no statistically significant difference in AEs profile of the 3 medications.
However, darolutamide had the highest SUCRA value and probability of being the most preferred medication based on AEs profile.
Conclusion:
Enzalutamide and apalutamide had similar and higher MFS rate in indirect comparison with darolutamide.
In cases where AEs are concerning, darolutamide might be the preferred agent.
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