Combination Therapy Shows Mixed Results in First Randomized Trial for Lung Cancer
A phase 2 clinical trial is hoping to determine if a combination therapy can be effective in treating patients with non-small cell lung cancer (NSCLC). A previous phase 1 trial evaluated the safety and efficacy of a combination of pembrolizumab and vorinostat. Now researchers at Moffitt Cancer Center are taking that study a step further with a first-line, phase 2 trial.
While at #ASCO23, Dr. Andreas Saltos discusses the final results of a phase II randomized trial of first-line pembrolizumab and vorinostat in patients with metastatic NSCLC.
— Moffitt Cancer Center (@MoffittNews) June 5, 2023
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Pembrolizumab is what’s known as a checkpoint inhibitor. It’s a type of drug that blocks certain proteins made by some types of immune system cells, such as T cells, and some cancer cells. These proteins help keep immune responses in check and can stop T cells from killing cancer cells. When these proteins are blocked, the “brakes” on the immune system are released and T cells can kill cancer cells better.
Vorinostat is in a class of medications called histone deacetylase (HDAC) inhibitors. These can be used to stop malignant cells from growing by modifying their expression of genes, in some cases attracting an immune response to the tumor and killing the cancer cells.
Dr. Andreas Saltos, a medical oncologist in Moffitt’s Thoracic Oncology Program, presented results from the trial trial at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.
“HDAC inhibitors have shown promise as a combination with immunotherapies in previous studies in lung cancer and other tumors,” Saltos said. “We’ve seen that this combination can sometimes invigorate that immune response, but this is the first randomized study looking at the combination of an HDAC inhibitor with immunotherapy in patients with NSCLC specifically.”
Researchers studied patients with newly diagnosed lung cancer with no prior treatment. Patients also had to have a PD-L1 expression of at least 1%, which is a common genetic marker that’s tested for at diagnosis.
The treatment was generally tolerable aside from some common side effects of vorinostat including nausea, fatigue and diarrhea. In some cases, patients reduced their dosage of vorinostat, which led to improvement in these symptoms.
In the study, 40 patients received pembrolizumab alone, while another 46 received a combination of pembrolizumab with vorinostat. Forty one percent of patients who received the combination therapy showed tumor shrinkage compared to 27% of patients who received pembrolizumab alone.
Although those numbers seem promising, there was no significant difference between the two groups in terms of progression-free survival or overall survival.
“Currently we’re taking a deeper dive into biopsies that we took before treatment to find out if there is a certain population that may benefit more than others and explain why we saw some responses and why it didn’t translate into a survival benefit,” Saltos said. “There’s more work to do but I think it’s an important study to have this combination tested in a randomized trial for the first time in lung cancer.”
