A 3-center studyusing viral therapy talimogene laherparepvec (TVEC; Imlygic) in advanced melanoma has reported some of the best patient response rates since the drug was approved by the US Food and Drug Administration (FDA) in 2015.1
The research involved patients from Emory University, Atlanta, Georgia; the Moffitt Cancer Center, Tampa, Florida; and The University of North Carolina (UNC), Chapel Hill; monitored between 2015 and 2018. It found that 39% of patients achieved a complete local response and 18% achieved a partial response to therapy, with follow-up times ranging from 3 months to 28 months.
This represents a significant improvement compared with the original OPTiM trial,2 which led to the FDA approval of TVECand shows that the use of the therapy translates well to “real-world” use in cancer centers outside of the well-defined parameters of a clinical trial. However, just under half of patients don’t respond to TVEC at all, and the next big step to increasing its efficacy is to find out why.
“The concept right now is that not every tumor is as immunogenic as we would hope it to be. Not every tumor when you use TVEC becomes a ‘hot tumor’, and the immune response is brisk. Some remain ‘cold’ and we don’t get the response that we want,” said David Ollila, MD, senior author of the paper and professor of surgical oncology in the department of medicine at UNC.
This hot and cold metaphor refers to whether tumors are likely to be tackled by the immune system after TVEC administration — hot tumors responding well, but cold tumors don’t respond to therapy. There’s currently no way to stratify which patients will have hot tumors and are going to respond well to TVEC.
“We are trying to understand this switch. How can we make a cold tumor hot, or how can we define better upfront which tumors are hot?” pondered Dr Ollila.
The study included 121 patients who received TVEC; 80 of these whom were followed for at least 3 months after treatment and had treatment response data available for analysis. Of the 31 patients who achieved a complete local response, 29 patients had no evidence of disease at their last recorded follow-up appointment.
The original OPTiM trial reported an 11% complete response rate — and at a 39% response rate, the new study represents a considerable improvement to the former response rate. The therapy itself hasn’t changed, so the reason for this increase in response is likely due to one, main factor: stratification of patients based on the staging of their disease.
“When you go back to the original OPTiM trial, they included everyone with several stagings of disease, when they looked back at subset analysis, the patients who had the best chance of responding were staged 3C, 3B, or M1A — we just went after these. That’s why you see a higher response rate in our trial. We went after the patients we thought would do the best,” said Dr Ollila.
A particularly notable success of TVEC appears to be that it can be used at any body site where melanomas develop, even if it occurs in an area that would typically be unsuitable for surgical intervention.
“TVEC allows you to go anywhere in the body that you can have access to. This is a really good therapy for use in all places, not just the extremities,” said Dr Ollila.