Panobinostat activity in both bexarotene-exposed and -naïve patients with refractory cutaneous T-cell lymphoma: Results of a phase II trial

• Published in: European journal of cancer (1990) 2013-01, Vol.49 (2), p.386-394
• Main Authors: Duvic, Madeleine, Dummer, Reinhard, Becker, Jürgen C, Poulalhon, Nicolas, Ortiz Romero, Pablo, Grazia Bernengo, Maria, Lebbé, Celeste, Assaf, Chalid, Squier, Margaret, Williams, Denise, Marshood, Miriam, Tai, Feng, Prince, H. Miles
• Format: Article
• Language: English
• Subjects: Anticarcinogenic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Bexarotene; Biological and medical sciences; Cutaneous T-cell lymphoma; Disease Progression; Disease-Free Survival; Female; Hematology, Oncology and Palliative Medicine; Histone Deacetylase Inhibitors - adverse effects; Histone Deacetylase Inhibitors - therapeutic use; Humans; Hydroxamic Acids - adverse effects; Hydroxamic Acids - therapeutic use; Indoles - adverse effects; Indoles - therapeutic use; Male; Medical sciences; Middle Aged; Mycosis fungoides; Mycosis Fungoides - drug therapy; Mycosis Fungoides - pathology; Pan-deacetylase inhibitor; Panobinostat; Pharmacology. Drug treatments; Sezary Syndrome - drug therapy; Sezary Syndrome - pathology; Skin Neoplasms - drug therapy; Skin Neoplasms - pathology; Sézary syndrome; Tetrahydronaphthalenes - administration & dosage; Tumors
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2012.08.017

Abstract Background Panobinostat is a potent, oral pan-deacetylase inhibitor (pan-DACi) that increases the acetylation of proteins involved in multiple oncogenic pathways. Here, panobinostat is studied in bexarotene-exposed and -naïve patients with refractory cutaneous T-cell lymphoma (CTCL). Patients and methods Patients with CTCL subtypes mycosis fungoides and Sézary syndrome who received ⩾2 prior systemic therapy regimens received panobinostat (20 mg) three times every week. The primary objective was overall response rate (ORR) as determined by a combined evaluation of skin disease and involvement of lymph node and viscera. Disease progression was defined as an unconfirmed, ⩾25% increase in modified Severity Weighted Assessment Tool (mSWAT) compared with nadir. Results Seventy-nine bexarotene-exposed and 60 bexarotene-naïve patients were enrolled. Reductions in baseline mSWAT scores were observed in 103 patients (74.1%). The ORR was 17.3% in all patients in the primary analysis (15.2% and 20.0% in the bexarotene-exposed and -naïve groups, respectively). The median progression-free survival was 4.2 and 3.7 months in the bexarotene-exposed and -naïve groups, respectively. The median duration of response was 5.6 months in the bexarotene-exposed patients and was not reached at data cutoff in the bexarotene-naïve patients. Additional responses were observed when less-stringent progression criteria were used. The most common adverse events were thrombocytopenia, diarrhoea, fatigue and nausea. Thrombocytopenia and neutropenia were the only grade 3/4 adverse events in >5% of patients and were manageable. Conclusion Despite a very conservative definition of disease progression, panobinostat demonstrated activity with a manageable safety profile in bexarotene-exposed and -naïve CTCL patients. ClinicalTrials.gov Identifier: NCT00425555.