In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 5076-5076
Abstract:
5076 Background: Ortl is a selective, non-steroidal, oral 17,20-lyase inhibitor. Due to its lower inhibition of 17α-hydroxylase vs 17,20-lyase, ortl may allow steroid-free dosing. Ortl 300 mg BID was studied in nmCRPC patients (pts). Methods: Pts with nmCRPC, PSA ≥2 ng/mL (PSA ≥8 ng/mL if doubling time 〉 8 mo), and testosterone (T) 〈 50 ng/dL received ortl 300 mg BID until PSA progression, development of metastases (mets), or unacceptable toxicity. Primary endpoint: the percentage of pts with PSA ≤0.2 ng/mL at 3 mo. Secondary endpoints included safety, PSA kinetics, time to mets, and PFS (PSA progression, mets, or death), endocrine and bone markers, bone mineral density (BMD), HRQoL, cardiac and lipid assessments. Results: 38 pts enrolled: median PSA 11.7 ng/mL (range 2.6–67.8), T 8.5 ng/dL (1.4–17.3), and ACTH 20 ng/L (n=32; 0–47). Median therapy duration was 12.4 mo (0.7–27.8); 55% of pts were treated 〉 12 mo. 6 had dose reduction, 12 discontinued due to adverse events (AEs), including 2 for possible adrenal insufficiency. Gr 3 hypertension occurred in 7 pts (18%); various ≥Gr 3 AEs occurred in another 14 pts; 10 pts (26%) had serious AEs. At 3 mo, median T declined 89% to 0.78 ng/dL; median ACTH increased 171%; median cortisol declined 21%, but remained within normal range. 97% of pts had PSA declines; median PSA declined 83%. 18% had PSA ≤0.2ng/mL at 3 mo; 32% achieved PSA ≤0.2ng/mL as best response. Median time to PSA progression was 13.8 mo. Median PFS was 13.8 mo. Kaplan-Meier estimates of 1 and 2 y mets-free rates were 94% and 69%, respectively; 8 pts developed mets on study. The patient-reported Aging Male Symptoms Scale showed no decrease in overall scores, psychological, somatic, or sexual domains in 37, 34, 25, and 19 pts assessed at visits 2, 4, 7, and 13, respectively. Serum lipids, cardiac assessments, HbA 1C , or bone-specific enzymes (N-telopeptide, or BMD) were not adversely affected. Conclusions: In pts with nmCRPC, long-term steroid-free ortl was feasible, with clinical activity as reflected by sustained marked declines in PSA and T, and had manageable toxicities, with no adverse effects on HRQoL, cardiac, bone or lipid profiles. Clinical trial information: NCT01046916.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.15_suppl.5076
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2013
detail.hit.zdb_id:
2005181-5
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