Darotamide combined with ADT improves survival in patients with hormone-sensitive metastatic prostate cancer

This article is from the NEJM Journal Watch, Intensification of ADT in Hormone-Sensitive Metastatic Prostate Cancer: An Evolving Paradigm.
ADT Intensification in Hormone-Sensitive Metastatic Prostate Cancer: A Review of Evolving Treatment Options by Robert Dreicer, MD, MS , MACP, FASCO Addition of dalotamide to androgen deprivation therapy combined with docetaxel improves survival
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Androgen deprivation enhanced with docetaxel, abiraterone, enzalutamide, or apalutamide for most patients with hormone-sensitive metastatic prostate cancer (HSMPC), based on a solid survival benefit shown in a phase 3 study Therapy (ADT) is the standard of care
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The PEACE-1 trial demonstrated the benefit of adding abiraterone to ADT plus docetaxel in patients with high-risk metastatic prostate cancer at presentation (Ann Oncol 2021; 32:suppl 5:S1283)
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In the industry-funded, international phase 3 ARASENS trial, investigators randomly assigned patients with HSMPC to receive either dalosamide or placebo in addition to ADT plus docetaxel
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Randomization was stratified according to TNM stage of metastasis
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The primary endpoint was overall survival
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Of the 1,306 patients, at initial presentation, 80% had bone metastases, 18% had visceral metastases, and 86% had metastatic prostate cancer
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At the time of data cutoff, the median duration of treatment was 41.
0 months in the dalotamide group compared with 16.
7 months in the placebo group
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87% of patients in both groups completed 6 cycles of docetaxel
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The risk of death was 32.
5% lower in the darotamide group than in the placebo group (hazard ratio, 0.
68; P<0.
001)
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The 4-year overall survival rate was 62.
7% in the dalotamide group and 50.
4% in the placebo group
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Notably, 76% of patients in the placebo group received subsequent treatments that might prolong survival
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Grade 3 or 4 adverse events occurred in 66.
1% and 63.
5% of patients in the darotamide and placebo groups, respectively, the most common being neutropenia (approximately 34%)
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Commentary These results support the findings of the PEACE-1 study that in selected patients with HSMPC, ADT combined with docetaxel can be further intensified with androgen receptor pathway inhibitors
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All participants in PEACE-1 and most participants in ARASENS were patients with metastatic prostate cancer who were presentation-naive and eligible for docetaxel
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We need more data to assess the potential benefit for other HSMPC patient populations
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Reviewed article Smith MR et al.
Darolutamide and survival in metastatic, hormone-sensitive prostate cancer.
N Engl J Med 2022 Feb 17; [e-pub].
(https://doi.
org/10.
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