"Dose reduction for patients with small body size may alleviate skin AEs without sacrificing oncological outcomes,” said Kyo Togashi.
The incidence of skin-related adverse events (AEs) following dose-reduced treatment with apalutamide (Erleada) did not significantly decrease compared with the full dose of the agent, among men with advanced prostate cancer, according to data from a multicenter, retrospective study presented at the 2023 American Urological Association Annual Meeting.1
“However, dose reduction for patients with small body size may alleviate skin AEs without sacrificing oncological outcomes,” Kyo Togashi, from the Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan, said during his presentation.
According to the study investigators, 51.47% of patients in the study of Japanese patients who were treated with apalutamide experienced skin-related AEs, compared with just 23.8% in the phase 3 SPARTAN trial (NCT01946204) and 27.1% of patients in the phase 3 TITAN trial (NCT02489318).2 Therefore, a sub-analysis was conducted of the clinical trial, from which it was shown that the small body size of Japanese patients may lead to higher levels of the agent in blood.3
In their study, Togashi and colleagues aimed to evaluate if the dose reduction of apalutamide would affect skin-related AEs and CRPC-free survival in 107 patients with metastatic castration-sensitive prostate cancer (mCSPC; n = 72) or nonmetastatic castration-resistant prostate cancer (nmCRPC; n = 35) who were diagnosed between June 2019 and June 2022.
Of the 65 patients treated with the full dose of 240 mg apalutamide, 42 were dose reduced to receive a range between 60 mg to 180 mg.
The incidence rate of skin-related AEs served as the primary end point; secondary end points included skin AEs among patients with small body size and treatment discontinuations in patients with mCSPC who were treated with upfront apalutamide plus androgen deprivation therapy.
The investigators observed that skin-related AEs occurred in 55.4% of patients in the full-dose group (n = 36), including 44.6% that were grade 1 to 2 and 10.8% that were grade 3 to 5, compared with 42.9% of patients in the dose-reduction group (n = 18), including 38.1% that were grade 1 to 2 and 4.8% that were grade 3 to 5, which, overall, was not a statistically significant difference (P = .761). Similarly, skin-related AE-free survival was not statistically different (undefined in the dose-reduction group vs 4.6 months in the full-dose group; P = .33).
However, among patients with a small body size (body weight, <67 kg; body mass index [BMI], <24 kg/m2), dose reductions led to a lower incidence rate of skin-related AEs, compared with the full dose (46% vs 74%, respectively; P = .032).
Further, only 50% of patients treated with the full dose of apalutamide continued treatment, whereas 83.3% of patients in the dose-reduction arm continued on therapy (P = .021).
Lastly, patients with mCSPC, as well as those with or without skin-related AEs did not demonstrate a difference in CRPC-free survival between dose groups.
1. Togashi K, Hatakeyama S, Tabata R, et al. The effect of a reduced dose of apalutamide on skin-related adverse events in advanced prostate cancer: A multicenter retrospective study. J Urol. 2023;209(4):e130. doi:10.1097/JU.0000000000003226.15
2. Uemura H, Koroki Y, Iwaki Y, et al. Skin rash following Administration of Apalutamide in Japanese patients with Advanced Prostate Cancer: an integrated analysis of the phase 3 SPARTAN and TITAN studies and a phase 1 open-label study. BMC Urol. 2020;20(1):139. doi:10.1186/s12894-020-00689-0
3. Uemura H, Satoh T, Tsumura H, et al. Efficacy and safety of apalutamide in Japanese patients with nonmetastatic castration-resistant prostate cancer: a subgroup analysis of a randomized, double-blind, placebo-controlled, Phase-3 study. Prostate Int. 2020;8(4):190-197. doi:10.1016/j.prnil.2020.05.002