Effectiveness of first-line abiraterone versus enzalutamide among patients ≥80 years of age with metastatic castration-resistant prostate cancer: A retrospective propensity score-weighted comparative cohort study.

BACKGROUND

Metastatic castration-resistant prostate cancer (mCRPC) disproportionately affects the elderly. There is limited data assessing the efficacy and tolerability of abiraterone acetate (AA) versus enzalutamide in this population.

OBJECTIVE

To compare the clinical efficacy and tolerability of AA versus enzalutamide in patients ≥ 80 years with mCRPC.

DESIGN, SETTING AND PARTICIPANTS

A retrospective propensity-weighted comparative cohort study of first-line AA versus enzalutamide among patients with mCRPC aged ≥80 years.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS

Inverse probability treatment weights based on propensity scores were generated to assess the treatment effect of AA versus enzalutamide on time to PSA progression (TTPP), time to progression (TTP) (first of PSA/radiographic/clinical progression) and overall survival using a weighted Cox proportional hazards model. PSA response rate (PSA RR) was compared between groups using Χ

RESULTS AND LIMITATIONS

One hundred fifty-three patients received AA, and 125 received enzalutamide. Enzalutamide was associated with higher PSA RR (61.6% vs 43.8%, P < 0.004), and TTP (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.50-0.88, P = 0.01) but not TTPP (HR 0.73, 95% CI 0.53-1.01, P = 0.06). There were significantly more dose reductions with enzalutamide (22.9% vs 44.8%, P > 0.001) but there was no interaction between median proportion of full dose received and TTPP or TTP for either drug. Rates of treatment discontinuation (for reasons other than progression) were also significantly different between AA and enzalutamide (28.8% vs 40.8%, respectively, P = 0.04). The most common reason for dose reductions and discontinuation of enzalutamide was fatigue (30.4% and 5.6%, respectively).

CONCLUSIONS

Despite more dose reductions and a higher treatment discontinuation rate, enzalutamide was associated with a higher PSA RR and longer time to progression, than AA. Given that clinical outcomes were not adversely impacted by decreased treatment exposure, dose modification may be a useful treatment strategy to balance toxicity and tolerance.

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M. Soleimani has received honoraria from Pfizer and grant funding from Bayer, Abbvie and Astellas. B.J. Eigl has received honoraria from Pfizer, Janssen, AstraZeneca, Merck, Roche, Bayer. L Nappi has received honoraria from Ipsen and Bayer. C.K. Kollmannsberger has received honoraria from Pfizer, Astellas, Janssen, Merck, Eisai, Ipsen, Bristol Myers Squibb, and served on advisory board for Pfizer, Astellas, Janssen, Merck, Eisai, Ipsen, EMD Serono, Bristol Myers Squibb. D. Finch has received honoraria from Janssen, Bristol Myers Squibb, Bayer, Astellas, Takeda and Roche. K Noonan has received research funding from Roche and has served in consulting and advisory roles for AstraZeneca, Bayer, Bristol Myers Squibb, Janssen. D.J. Khalaf has received consulting fees from Janssen. K.N. Chi has received honoraria and grants from Novartis, Janssen, Astellas, Sanofi, AstraZeneca, Bayer, Pfizer, Roche, Daiichi Sankyo, Point Biopharma. All remaining authors have declared no conflicts of interest.