Dr Saltos on Pembrolizumab Plus Vorinostat in mNSCLC

Andreas Saltos, MD, medical director, Clinical Research, Department of Thoracic Oncology, Moffitt Cancer Center, discusses final results from a phase 2 trial (NCT02638090) of first-line pembrolizumab (Keytruda) plus vorinostat (Zolinza) in patients with metastatic non–small cell lung cancer (mNSCLC).

Dr Saltos on the Efficacy of Pembrolizumab Plus Vorinostat in mNSCLC

A phase 2 trial randomly assigned patients with treatment-naïve mNSCLC to receive pembrolizumab with or without the histone deacetylase inhibitor vorinostat. The primary end point of this trial was overall response rate (ORR), with duration of response, progression-free survival (PFS), and overall survival (OS) as key secondary end points.

In this trial, pembrolizumab plus vorinostat elicited a numerically higher ORR compared with pembrolizumab monotherapy, although this difference was not statistically significant, Saltos says. Of the evaluable patients, the ORR was 44% in the combination arm vs 28% in the monotherapy arm (P = .18). In the monotherapy arm, 37.5% and 35% of patients had best responses of stable disease (SD) and progressive disease (PD), respectively. In the combination arm, 32.6% and 19.6% of patients had best responses of SD and PD, respectively, and 6.5% were not evaluable. 

This numerically higher ORR in the combination arm did not translate to a statistically significant difference in PFS or OS, with log-rank P values of .8 and .49, respectively, according to Saltos.

Dr Saltos on Interferon Target Gene Increases With Pembrolizumab and Vorinostat in mNSCLC

The investigators evaluated RNA sequencing results from tumor biopsies obtained prior to treatment and 2 to 3 weeks after treatment initiation, Saltos explains. In this evaluation, both arms had significant increases in types I and II interferon pathways, as well as upregulations of the interferon target genes STAT1, CXCL9, and CXCL10, Saltos says. A significant difference in the downregulation of cell cycle proteins was observed between the 2 arms, which may be consistent with the mechanism of action of vorinostat, Saltos concludes.