Plasmapheresis as a promising treatment option in apalutamide‐associated toxic epidermal necrolysis

Miyagawa, Akihiro; Adachi, Takeya; Kobayashi, Yuki; Takamiyagi, Saeko; Arakawa, Hiroki; Futatsugi, Koji; Inazumi, Toyoko

doi:10.1111/1346-8138.16248

Cited by 7 publications

(11 citation statements)

References 5 publications

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“…Of those, one patient had grade 5 toxic epidermal necrolysis. Currently, three cases of apalutamide‐associated toxic epidermal necrolysis have been reported 6 . As toxic epidermal necrolysis is associated with significant mortality (30–50%), 7 we need to pay attention to the danger signs of mucous membrane rash and fever, to detect them as early as possible.…”

Section: Figmentioning

confidence: 99%

Impact of body size on skin‐related adverse events in advanced prostate cancer treated with apalutamide: A multicenter retrospective study

et al. 2022

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ADT plus apalutamide has a significant benefit in treating mCSPC and nmCRPC. 1,2 However, the rate of skin-related AEs of apalutamide in Japanese patients was higher (51.47%) 3 than that of data from Phase 3 trials (23.8-27.2%). 1,2 A previous pharmacokinetic study suggested that the smaller BW might be associated with higher apalutamide concentration. 4 However, little is known about the impact of body size on skin-related AEs.Between June 2019 and September 2021, we evaluated 48 patients with nmCRPC or mCSPC who received apalutamide (240 mg) in the Hirosaki University Hospital or our related hospitals. We evaluated the incidence of skin-related AEs after the apalutamide administration and the risk factors for skin-related AEs. This study was approved by the ethics committee of Hirosaki University School of Medicine and all related hospitals (2019-099-1).Of 48 patients, we identified 25 and 23 patients with nmCRPC and mCSPC, respectively. The median age was 73 (interquartile range 70-78) years. We found 27 (56%) patients had skin-related AEs in this cohort. The median skin-related AEs was grade 2 (interquartile range 1-2). Eight patients (30%) discontinued apalutamide due to skin-related AEs, three patients (11%) discontinued apalutamide due to disease progression, and 16 patients (59%) restarted with a reduced dose of apalutamide (Fig. 1a). Of 27, four patients (15%) had grade 3 and one patient (3.7%) had grade 5 skin AE (toxic epidermal necrolysis). The median time to the incidence of skin-related AEs was 6.9 months (Fig. 1b). There was no significant difference in background between the patients with and without skin-related AEs, except for the BW (69 vs 62 kg, respectively, Fig. 1c) and BMI (25.0 vs 22.2 kg/m 2 , respectively, Fig. 1d). The area under the receiver operating characteristic curve showed the cutoff value of BW and BMI as 67 kg and 24 kg/m 2 , respectively (Fig. 1e). When we developed the combination of BMI and BW (body-size risk score), the patients with BW <67 kg and BMI <24 kg/m 2 had significantly higher skin AEs rate (83%) than those without (32%, P < 0.001, Fig. 1f). A visual abstract is shown in Figure S1.We observed 56% of skin-related AEs related to the use of apalutamide, which was similar to the subgroup analysis of Japanese patients in the SPARTAN (56%) and TITAN (50%) trials. 3 Also, a subgroup analysis of the TITAN trial in East Asia reported the incidence of skin rash in 37.3%, which was slightly lower than the Japanese patients. 5 Therefore, the skin toxicity of apalutamide might be higher in the Japanese patients than that in other population.A previous pharmacokinetic analysis of the SPARTAN trial showed that apalutamide concentration was higher in the Japanese subpopulation compared to the non-Japanese population, which was related to small body size. 4 As we expected, our data showed that body size can be the risk factor for skin-related AEs. Although further study is necessary, caution is necessary for administration of apalutamide in patients with small body sizes.The s...

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Section: Figmentioning

confidence: 99%

Impact of body size on skin‐related adverse events in advanced prostate cancer treated with apalutamide: A multicenter retrospective study

et al. 2022

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“…In clinical trials the incidence of adverse skin events due to apalutamide was nearly double in the Japanese population compared with the global population ( 4 ). To date, 4 cases of TEN caused by this agent have been reported ( 1 – 3 ) ( Table I ). Although all 4 cases were Japanese, further investigations are required to elucidate the differences in incidence among races.…”

Section: Discussionmentioning

confidence: 99%

“…Apalutamide is an androgen receptor inhibitor used for treatment of prostate cancer. It occasionally causes severe cutaneous disorders, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) ( 1 – 3 ). We report here a case of TEN caused by apalutamide, which was treated successfully using etanercept with conventional therapies.…”

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confidence: 99%

Toxic Epidermal Necrolysis Caused by Apalutamide: A Case Report of Treatment Using Etanercept with Conventional Steroid Therapy

et al. 2022

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“…Among the TEN cases, four (66.7%) had fatal outcomes, [7][8][9][10][11] although plasmapheresis temporally improved cutaneous adverse events. 7,9,10 In contrast, 33 mild cases had favorable outcomes. Representative LTT was performed in seven of 33 mild cases and four of eight severe cases.…”

Section: Re Sultsmentioning

confidence: 98%

Characteristics of mild and severe apalutamide‐related cutaneous adverse events in patients with prostate cancer: A review of the literature

Katsuta,

Nobeyama,

Hirafuku

et al. 2023

The Journal of Dermatology

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Apalutamide is an antiandrogen used to treat prostate cancer. Although it sometimes induces mild cutaneous adverse events and occasionally severe ones, clinical differences between severe and mild cases remain unclear. To assess the risks in patients experiencing apalutamide‐related cutaneous adverse events (ARCAEs), we aimed to characterize severe and mild ARCAEs in terms of onset time and lymphocyte transformation test (LTT) for apalutamide. We reviewed 41 ARCAE cases: 24 from our institute and 17 from the literature, comprising (i) eight severe cases including six with toxic epidermal necrolysis, one with acute generalized exanthematous pustulosis, and one with drug reaction with eosinophilia and systemic symptoms, and (ii) 33 mild cases. Patients with evere cases developed ARCAEs significantly earlier than patients with mild cases (5.2 vs 9.6 weeks). No severe cases appeared ≥8 weeks after initiation of apalutamide. LTTs showed positive results in two of seven mild cases (28.6%) and four of four severe cases (100.0%). In conclusion, we found that severe ARCAEs are characterized by earlier onset and LTT positivity. Dermatologists and urologists should pay special attention to patients who develop ARCAEs <8 weeks after initiating apalutamide and/or show positive LTT results.

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Plasmapheresis as a promising treatment option in apalutamide‐associated toxic epidermal necrolysis

Cited by 7 publications

References 5 publications

Impact of body size on skin‐related adverse events in advanced prostate cancer treated with apalutamide: A multicenter retrospective study

Impact of body size on skin‐related adverse events in advanced prostate cancer treated with apalutamide: A multicenter retrospective study

Toxic Epidermal Necrolysis Caused by Apalutamide: A Case Report of Treatment Using Etanercept with Conventional Steroid Therapy

Characteristics of mild and severe apalutamide‐related cutaneous adverse events in patients with prostate cancer: A review of the literature

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