1. Compare PEACE 1 trial with ARASENS trial?
Abiraterone added to docetaxel and ADT improved rPFS and OS. Hypertension was higher in abiraterone but neutropenia, fatigue, neuropathy, and sepsis were not increased. This was for patients with high volume disease and data are immature for low vol disease. The median OS in Chaarted trial with docetaxel +ADT was 55 months which is 4.5 years, the same as in the SOC arm ( docetaxel with ADT). The median OS was not reached in the triplet arm.
- Median progression-free survival was 4.46 in the triplet abiraterone arm vs 2.03 years, and median overall survival was not reached vs 4.43 years.
ARASENS: Darolutamide median OS not reached versus 45 months ( shy of 4 yr). Clear improvement in OS and all secondary factors such as rPFS, time to first skeletal event, time to next antineoplastic therapy. AE coincided with docetaxel administration.
2. Compare ARCHES versus ENZAMET trial?
Arches compared enzalutamide versus placebo in hormone sensitive met prostate ca. Although OS was not improved, multiple other factors including radiographic progression, PSA rise and initial skeletal events, pain progression were all less with enza compared to placebo with ADT. Prior docetaxel use was permitted. Low volume disease patients also benefited. Approx 24% grade 3 or higher AE.
Enzamet was similar to Arches trial but had a triplet arm with docetaxel.
3. CHAARTED trial OS: docetaxel with ADT 55 months OS, 13 months more than ADT alone in high volume disease.
4. What adverse effects should you be concerned in patients on AR inhibitors?
These include fatigue, falls, fractures, mental impairment, rash, hypertension, and cardiovascular events.
Darolutamide dose needs to be reduced for Child Pugh's B and Cr Cl 15-29. The dose is 300 mg BID.
During counseling for darolutamide: ask for symptoms of uncontrolled ischemic heart disease and other CV risk factors. Counsel about risk of seizures.
Apalutamide has an incidence of rash of 25%. This is more than for other AR inhibitors. Typically seen at 2.5 months.
Management: reference
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