Hossein Borghaei, DO
Results of studies of immunotherapy as a frontline therapy choice for patients with non–small cell lung cancer (NSCLC) are causing much excitement in the field, along with their potential use as part of combination strategies, reported Hossein Borghaei, DO, during his presentation at the recent 11th Annual New York Lung Cancer Symposium
Borghaei, who is chief of the Division of Thoracic Medical Oncology, director of Lung Cancer Risk Assessment, and associate professor in the Department of Hematology/Oncology at Fox Chase Cancer Center, sat down with OncLive
at the Symposium to discuss what lies ahead for immunotherapy in lung cancer, and what changes may be on the horizon for such agents as pembrolizumab, nivolumab, and ipilimumab in the frontline setting. He also stressed the importance of the patient’s quality of life when considering new agents and ensuring that the efficacy of the drug outweighs any increased toxicity.
OncLive: What do oncologists need to know about the use of immunotherapies in the frontline setting?
: I think it is well-established that all of these immuno-oncology drugs have an active role in treatment of patients for recurrent NSCLC. Head-to-head, versus chemotherapy, all of these are a lot more effective and a lot less toxic. I think in the second-line setting, we've established that.
In the frontline setting, up until recently we didn't have any data. But at the ESMO meeting just 6 weeks ago, the results of a frontline study using pembrolizumab in patients with really high expression of PD-L1 in their tumor, over 50% basically, were extremely encouraging and practice-changing, to the extent that, at least at my institution, we now routinely check everybody's tumor expression for PD-L1, and if they fit this study's criteria, we use pembrolizumab.
In that study, pembrolizumab was compared head-to-head versus standard platinum doublet chemotherapy. And both progression-free survival (PFS) and overall survival (OS) were superior with pembrolizumab. There were no additional safety signals above and beyond what we've previously seen with pembrolizumab, suggesting a highly active drug with an acceptable side effect profile. That study, at the time of reporting, changed clinical practice in lung cancer, as far as I'm concerned, regardless of histology.
The question then is: what do we do for patients who have a lower expression of the PD-L1 marker in the frontline setting? As far as I'm concerned, in the absence of clinical trials, standard chemotherapy is the viable option there. That has led to a number of investigations.
I am a co-investigator on a study of pembrolizumab in combination with platinum doublet chemotherapy. This was a sub-arm of a larger study, a randomized phase II trial reported by Corey Langer, MD, where adding pembrolizumab to a backbone of carboplatin and pemetrexed actually did improve both response rate and PFS.1 Overall survival was the same at the time of reporting. But this study did not have adequate follow-up, so we have to wait and see what happens. There were no significant safety signals—a little more in terms of side effects, as you can imagine, adding a third drug to any platinum doublet. But overall, nothing significant above and beyond what we had expected.
The question is: Is that going to be a viable option for patients? The study was small, because it was a randomized phase II. We did look at PD-L1 expression. The signal is a little bit difficult to interpret, I think, because of the smaller number of patients in each subgroup. It is a possibility that the phase III study that's already ongoing with the same combination might show us that, for instance, in patients with low expression of PD-L1, maybe the combination with chemotherapy will be the way to go. We just don't know that yet. We have to wait for the trial results. So I would not combine chemo with an immuno-oncology agent outside of a clinical trial at this moment.
What about combining immunotherapies?
And then we started talking about immuno-oncology combinations. There have been a couple of studies that have been published already, including one in Lancet Oncology looking at durvalumab plus tremelimumab.2 Again a smaller number, but a study, after going through several different dosing and schedule of delivery of the agents, was able to come up with a combination most of us would consider fairly tolerable. Based on the published results, hopefully, it will be very effective.