303 Background: Enzalutamide (ENZA), an androgen receptor (AR) inhibitor that blocks multiple steps in the AR signaling pathway, is approved for patients (pts) with metastatic castration-resistant prostate cancer. This Phase 2, open-label, extension study (NCT01534052) evaluated long-term safety of continued ENZA administration. Methods: Prostate cancer pts previously treated with ENZA in Phase I studies (NCT01902251; NCT01911728; NCT02225093) continued to receive ENZA 160 mg/day until the investigator considered it no longer beneficial or consent was withdrawn. The primary end point was safety. Baseline data from the parent studies were used. Results: 52 pts were enrolled and received ENZA treatment (median age, 67 years [range, 54–88]). Median treatment duration was 443 days (range, 63–2010) since first administration and 392 days (range, 3–1926) in the extension study. In the extension, 43 pts (82.7%) experienced ≥1 any grade treatment-emergent adverse event (TEAE) with the most common (≥10% of pts) being fatigue (26.9% all grades, 13.5% grade 1, 7.7% grade 2, and 5.8% grade 3); arthralgia and back pain (13.5% each); and diarrhea, hot flush, and decreased appetite (11.5% each). Drug-related TEAEs (investigator assessed) were reported in 27 pts (51.9%) with the most common (≥5% of pts) being fatigue (17.3%); hot flush (11.5%); and diarrhea, hypophosphatemia, and muscle weakness (5.8% each). 17 pts (32.7%) had ≥1 serious TEAE. Eight drug-related serious TEAEs were reported in five pts (malignant neoplasm progression [3.8%]; acute pancreatitis, rectal haemorrhage, cerebrovascular accident, dysarthria, hemiparesis, and hypertensive crisis [1.9% each]). One (1.9%) death due to acute myocardial infarction (not drug-related) and four (7.7%) due to malignant neoplasm progression (two drug-related) were reported. No notable changes from baseline in clinical laboratory parameters or clinically meaningful abnormalities in vital signs, physical examinations, or electrocardiogram were found. Conclusions: Long-term continued ENZA treatment is generally well tolerated, with a safety profile consistent with that previously reported. Clinical trial information: NCT01534052.
Effects of Resmetirom on Noninvasive Endpoints in a 36‐Week Phase 2 Active Treatment Extension Study in Patients With
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