Highlights
- •Enzalutamide is approved for various indications in prostate cancer at 160 mg daily.
- •25% of patients discontinue treatment for adverse events and many require dose reduction.
- •Retrospective chart review of patients who started at lower dose.
- •Starting patients upfront on enzalutamide at 50% of recommended dose or less is safe and effective.
Abstract
Background
Enzalutamide is an important drug in the treatment of prostate cancer. Standard dosing
often requires dose reduction because of side effects. There is no information on
survival outcomes with lower doses. We investigated the impact of starting enzalutamide
at ≤ 50% dose on metastatic prostate cancer outcomes including patients' longevity.
Patients and Methods
Records of metastatic prostate cancer patients treated with enzalutamide at one center
were retrospectively reviewed. Low-dose enzalutamide (≤80 mg/day) was compared with
standard-dose (160 mg/day). The primary objective was to compute the restricted mean
survival time (RMST - time scale) and restricted mean attained age (RMAA - age scale)
using the Irwin method. Secondary objectives included overall survival (OS), progression-free
survival (PFS), and PSA progression per PCWG3 criteria (PSA PFS). We used the logrank
test and the ∆ difference between RMSTs for comparison.
Results
Of 111 patients treated, 32 received a low-dose and 79 the standard-dose. Low-dose
patients had less prior abiraterone or chemotherapy (28.1% vs. 65.8%, P < .001); more testosterone assessment (65.6% vs. 40.5%, P = .016); poorer ECOG performance status (48.3% score ≥2 vs. 26.6%; P = .040), more comorbidities (75.9% vs. 46.3%; P = .010)) including increased cardiovascular disease (51.7% vs. 21.4%, P = .004). Baseline PSA value and doubling time at start of enzalutamide and distribution
of metastases were similar between the groups. OS and PFS did not differ between low-dose
and standard-dose. Patients on low-dose had a better longevity with significantly
longer RMAA, 89.1 years, versus standard-dose RMAA of 83.8 years (∆ = 5.3 years, P = .003, logrank P = .025). In a subgroup analysis by age at start of enzalutamide, <75 versus ≥75 years
old, longevity was also better with low-dose in younger patients (∆ = 2.9 years, P = .034, and older, ∆ = 3.3 years, P = .011).
Conclusion
The longevity advantage and reduced adverse events seen in patients with prostate
cancer treated with low-dose enzalutamide warrants further investigation.
Keywords
Abbreviations:
CHUM (Centre Hospitalier Universitaire de Martinique), CT (Computed tomography), MDV3100 (initial code for enzalutamide), NCCN (National Comprehensive Cancer Network), OS (Overall survival), PET (Positron emission tomography), PFS (Progression-free survival), RMAA (Restricted mean attained age), RMST (Restricted mean survival time)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: June 06, 2022
Accepted:
May 30,
2022
Received in revised form:
January 8,
2022
Received:
March 1,
2021
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
