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 (

 = .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 

 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.

Videos

Andreas Saltos, MD, discusses final results from a phase 2 trial of first-line pembrolizumab plus vorinostat in patients with metastatic non–small cell lung cancer. 

Dr Saltos on Pembrolizumab Plus Vorinostat in mNSCLC

Andreas Saltos, MD, medical oncologist, clinical research medical director, Department of Thoracic Oncology, Moffitt Cancer Center, discusses the importance of broad molecular testing in non–small cell lung cancer (NSCLC).

In recent years, a number of effective targeted therapies have emerged for patients with molecular alterations that were not historically considered standard to test for, says Saltos. As such, molecular testing with broad genomic profiling has become important for all patients with advanced NSCLC, Saltos explains. 

Broad molecular testing may identify mutations for which no approved targeted therapies are available, Saltos says. However, ongoing clinical trials are evaluating numerous targeted therapies, so it is helpful to understand a patient’s full genetic make-up, Saltos says.

Notably, as the field of precision medicine continues to evolve in NSCLC, it is critical to test for mutations beyond 

Andreas Saltos, MD, discusses the importance of broad molecular testing in non–small cell lung cancer. 



Andreas Saltos, MD

Articles

Dr Saltos on Pembrolizumab Plus Vorinostat in mNSCLC

Dr. Saltos on the Importance of Broad Molecular Testing in NSCLC