Phase II trial of valproic acid combined with cisplatin-based chemoradiation in locally advanced (LA) head and neck squamous cell carcinoma (HNSCC) patients (pts)

• Published in: Journal of clinical oncology Vol. 35; no. 15_suppl; p. e17546
• Main Authors: Mak, Milena Perez, Pasini, Fatima Solange, Diao, Lixia, Garcia, Fabyane Oliveira Teixeira, Takahashi, Tiago Kenji, Amadio, Alex Vitorio, Siqueira, Sheila Aparecida Coelho, Sichero, Laura, Snitcovsky, Igor M. L., Kulcsar, Marco Aurelio Vamondes, Wang, Jing, Castro, Gilberto
• Format: Journal Article
• Language: English
• Published: 20.05.2017
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2017.35.15_suppl.e17546

Abstract only e17546 Background: Cisplatin-based chemoradiation (CRT) offers LA HNSCC pts a high local control rate, however, relapses are frequent. Here we evaluated if epigenetic regulation by VA, a histone deacetylase inhibitor (HDACi), combined with CRT in LA HNSCC improves response rate (RR). Methods: Patients with unresectable oropharynx (OP) and oral cavity LA HNSCC were included in this Simon two-stage phase II trial. After two weeks of VA (P1), CRT was initiated. Primary goal was RR at 8 weeks after CRT+VA (P2) by RECIST v 1.1. 8/20 and 25/32 responses were needed in the first and second stages for the trial to be considered positive (α = 0.05, β = 0.2). MicroRNA (miR) PCR-array profiling in plasma samples at baseline, P1 and P2, was compared to healthy controls by two sample t-test for each miR. Distribution of p-values was analyzed by beta-uniform mixture. HDAC2 and HR23B tumor immunohistochemistry were also evaluated. Results: Ten LA p16 negative OP pts were included. High-risk HPV was detected in 3 pts samples. Median age was 55 years (41-65). All pts were male, smokers or ex-smokers and with previous moderate/high alcohol intake. Due to significant toxicities seen in an interim safety analysis, accrual was terminated. A RR of 88% was achieved in 9 evaluable pts. A total of 169 miRs were differently expressed among pts and controls (FDR 0.05), including lower expression of known tumor suppressors (TS) such as miR-31, -222, -let-7b and -145. There were no significant differences in the pattern of miR expression at P1 vs. baseline. P2 vs. baseline had lower levels of miR-31, particularly in responders (p 0.007). TCGA HNSCC pts with low levels of miR-31 had a trend towards higher relapse free survival (HR 1.11, 95% CI 0.99-1.25; p = 0.073). Non-responders had no difference in miR expression between baseline and P2. HDAC2 H-score above 170 was 90% accurate in predicting 6-month disease free survival. Conclusions: Although improved RR was seen with VA+CRT, prohibitive toxicities prevented the trial from continuing. Cancer pts and controls had distinct pattern of miR expression, mainly with low levels of TS targeting TP53. miR-31 deregulation in HNSCC needs to be further elucidated. Clinical trial information: NCT01695122.