Efficacy and safety exposure–response relationships of apalutamide in patients with metastatic castration-sensitive prostate cancer: results from the phase 3 TITAN study

T’jollyn, Huybrecht; Ackaert, Oliver; Chien, Caly; Lopez-Gitlitz, Angela; McCarthy, Sharon; Ruixo, Carlos Pérez; Karsh, Lawrence I.; N., Kim; Ruixo, Juan-Jose Perez; Agarwal, Neeraj

doi:10.1007/s00280-022-04427-1

Cited by 11 publications

(10 citation statements)

References 24 publications

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“…This observation is supported by the finding of the previous post hoc Phase 3 TITAN trial that the difference in apalutamide exposure was not significantly associated with oncological outcomes 26 . Similar progression‐free survival and overall survival were radiographically observed between the lowest and highest apalutamide exposure quartiles in a pharmacokinetic analysis using the apalutamide area under the concentration curve for a duration of 24 h 26 . This finding also suggests that early apalutamide dose reduction owing to skin‐related AEs may not be detrimental to oncological outcomes.…”

Section: Discussionsupporting

confidence: 73%

“…We found no significant difference in the CRPC‐free survival rates between the full and reduced dose groups. This observation is supported by the finding of the previous post hoc Phase 3 TITAN trial that the difference in apalutamide exposure was not significantly associated with oncological outcomes 26 . Similar progression‐free survival and overall survival were radiographically observed between the lowest and highest apalutamide exposure quartiles in a pharmacokinetic analysis using the apalutamide area under the concentration curve for a duration of 24 h 26 .…”

Section: Discussionsupporting

confidence: 59%

“…TITAN trial that the difference in apalutamide exposure was not significantly associated with oncological outcomes. 26 Similar progression-free survival and overall survival were radiographically observed between the lowest and highest apalutamide exposure quartiles in a pharmacokinetic analysis using the apalutamide area under the concentration curve for a duration of 24 h. 26 This finding also suggests that early apalutamide dose reduction owing to skin-related AEs may not be detrimental to oncological outcomes. These results indicate that apalutamide dose reduction may be an effective method as an individual risk-benefit approach for balancing benefits and harms without sacrificing oncological outcomes.…”

Section: Discussionmentioning

confidence: 68%

“…This may be attributed to the apalutamide dose reduction without concentration measurement being insufficient as a personalized medicine or may be attributed to other non‐dose‐dependent causes. A post hoc analysis evaluating the relationship between apalutamide exposure and response in patients with mCSPC from the Phase 3 TITAN trial ( n = 1052) showed that the incidences of skin rashes and pruritus were significantly associated with increased apalutamide exposure 26 . Although it is difficult to predict the risk of developing skin‐related AEs based on apalutamide exposure alone, dose reduction may be beneficial for selected patients based on an individual risk–benefit approach.…”

Section: Discussionmentioning

confidence: 99%

“…A post hoc analysis evaluating the relationship between apalutamide exposure and response in patients with mCSPC from the Phase 3 TITAN trial (n = 1052) showed that the incidences of skin rashes and pruritus were significantly associated with increased apalutamide exposure. 26 Although it is difficult to predict the risk of developing skin-related AEs based on apalutamide exposure alone, dose reduction may be beneficial for selected patients based on an individual risk-benefit approach. Further study is warranted to select the optimal candidates for apalutamide dose reduction.…”

Section: Discussionmentioning

confidence: 99%

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Effects of apalutamide dose reduction on skin‐related adverse events in patients with advanced prostate cancer: A multicenter retrospective study

et al. 2022

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Background: We aimed to evaluate the effects of apalutamide dose reduction on skin-related adverse events (AEs) and castration-resistant prostate cancer (CRPC)free survival in patients with advanced prostate cancer (PC).Methods: We retrospectively evaluated 35 patients with nonmetastatic CRPC and 72 patients with treatment-naïve metastatic castration-sensitive PC (mCSPC) who were treated with apalutamide. The primary outcome was the effect of apalutamide dose reduction on skin-related AEs. The secondary outcomes were the effect of apalutamide dose reduction on skin-related AEs in patients with small body size, postskin AE apalutamide discontinuation rate, and CRPC-free survival in patients with mCSPC treated with upfront apalutamide plus androgen deprivation therapy.Results: Of the 107 patients, 65 (60.7%) and 42 (39.3%) were treated with full and reduced doses of apalutamide, respectively. The skin-related AE rate was not significantly different between the groups (55% vs. 43%, p = 0.761). In the group receiving reduced apalutamide dose, the incidence of skin-related AEs was significantly lower in patients with small body sizes (body weight <67 kg and body mass index <24 kg/m 2 ) than in those with other body sizes. The postskin AE apalutamide discontinuation rate was significantly differed between patients receiving the full (50%) and reduced (16.7%) doses. In the 72 patients with mCSPC, CRPC-free survival was not significantly different between the full and reduced dose groups.Conclusion: Apalutamide dose reduction was not significantly associated with the incidence of skin-related AEs. However, dose reduction in patients with small body sizes may alleviate skin-related AEs without sacrificing oncological outcomes.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Effects of apalutamide dose reduction on skin‐related adverse events in patients with advanced prostate cancer: A multicenter retrospective study

et al. 2022

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Severe neutropenia caused by palliative radiation therapy in a case of metastatic hormone‐sensitive prostate cancer

Maesaka,

Tomioka,

Matsushita

et al. 2024

IJU Case Reports

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IntroductionRadiotherapy for widespread bone metastasis results in severe hematological toxicity.Case presentationA 71‐year‐old male was diagnosed with metastatic hormone‐sensitive prostate cancer (cT4N1M1b) and treated with apalutamide and degarelix. Concurrently, palliative radiation therapy was sequentially initiated for the 1st, 5th, and 10th thoracic vertebrae and right femur. On day 35 after treatment, severe neutropenia necessitated treatment interruption and required 23 days for neutrophil recovery with a granulocyte colony‐stimulating factor agent.ConclusionOwing to the severe hematologic toxicity caused by extensive radiation therapy for multiple bone lesions, treatment prioritization by lesion and avoiding irradiation of the red bone marrow is essential.

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Real-world analysis of apalutamide-associated skin rash in Chinese patients with prostate cancer

Yang,

Shao,

Huang

et al. 2024

World J Urol

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Efficacy and safety exposure–response relationships of apalutamide in patients with metastatic castration-sensitive prostate cancer: results from the phase 3 TITAN study

Cited by 11 publications

References 24 publications

Effects of apalutamide dose reduction on skin‐related adverse events in patients with advanced prostate cancer: A multicenter retrospective study

Effects of apalutamide dose reduction on skin‐related adverse events in patients with advanced prostate cancer: A multicenter retrospective study

Severe neutropenia caused by palliative radiation therapy in a case of metastatic hormone‐sensitive prostate cancer

Real-world analysis of apalutamide-associated skin rash in Chinese patients with prostate cancer

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