Low-Dose Enzalutamide in Metastatic Prostate Cancer-Longevity Over Conventional Survival Analysis.

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.

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.

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).

The longevity advantage and reduced adverse events seen in patients with prostate cancer treated with low-dose enzalutamide warrants further investigation.

Clinical genitourinary cancer. 2022 Jun 06 [Epub ahead of print]

Vincent Vinh-Hung, Olena Gorobets, Gilles Natchagande, Paul Sargos, Ming Yin, Nam P Nguyen, Claire Verschraegen, Edmund Folefac

Centre Hospitalier Universitaire de Martinique, Fort-de-France, Martinique, France., Universitair Ziekenhuis Brussel, Brussels, Belgium., Centre National Hospitalier Universitaire Hubert K. MAGA, Cotonou, Benin., Département de radiothérapie, Institut Bergonié, Bordeaux, France., Ohio State University Comprehensive Cancer Center, Columbus, OH., Howard University, Washington, DC., Ohio State University Comprehensive Cancer Center, Columbus, OH. Electronic address: .

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