Vorinostat provides prolonged safety and clinical benefit to patients with advanced cutaneous t-cell lymphoma (CTCL)

Abstract

14588 Background: Vorinostat, a histone deacetylase inhibitor, was approved in 2006 by the FDA for the treatment of the cutaneous manifestations of CTCL in patients with progressive, persistent, or recurrent disease on or following 2 prior systemic therapies. Methods: Patients with stage ≥IIB CTCL who had received ≥two prior therapies and recovered from all prior treatment-related toxicities were eligible for an open-label, Phase IIb trial of oral vorinostat 400 mg daily. Patients took study medication until intolerable toxicity or progressive disease (PD). The primary endpoint was objective response rate as measured by the severity weighted assessment tool. Time to response, duration of response, safety and tolerability were also evaluated. This post hoc subset analysis reports results from patients who received vorinostat therapy for ≥2 years as of 11/1/07. Results: Six of 74 patients in the original study had received vorinostat therapy for ≥2 years as of 11/1/07, including five responders (one complete response, four partial responders) and one with stable disease. The median age was 65 years (range, 57–74), the median number of prior therapies was 2.5 (range, 1–5), and the median time from CTCL diagnosis to enrollment was 1.8 years (range, 0.7–5.9). Diarrhea (100%), nausea (83%), fatigue (67%), and alopecia (50%) were the most common drug-related adverse events (AEs) as determined by study investigator. The only serious AE was pulmonary embolism, which resolved in 7 days and patient is continuing therapy as of Day 955. Grade ≥3 AEs were anorexia (n=1), increased creatinine phosphokinase (CPK, n=1), rash (n=1), and thrombocytopenia (n=1). One patient experienced both increased CPK (Day 490) and rash (Day 645), and remained on therapy until Day 948. One patient discontinued due to PD, one discontinued due to PD, rash and increased CPK, and four are continuing on therapy as of 11/1/07. Updated data on these patients will be presented. Conclusions: Vorinostat has demonstrated prolonged safety and clinical benefit in these patients with advanced CTCL. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck Merck Merck Merck