VIDEO: Improving immune checkpoint inhibitor use in EGFR-mutated lung cancer

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We have a number of excellent frontline therapies, even more so now than ever for our patients with EGFR or mutant lung cancer. However, the sad truth is that disease progression, resistance to our therapies is unfortunately inevitable. It's this never ending challenge with therapy resistance and to kind of really to speak to that, immunotherapy, immunotherapy has really been kind of a game changer for the treatment of lung cancer but again, what's really challenging in the context of EGFR mutant lung cancer is that while immunotherapy has been highly effective for a lot of patients with wild type tumors especially those with high PD-L1, those patients with EGFR disease, their tumor microenvironment typically is what they call quote unquote cold. It's not immunoreactive. Doesn't respond well to immunotherapy. And while we might see a patient with kind of a smoking induced tumor, tumors with high PD-L1 have long lasting durable responses to immunotherapy, to checkpoint inhibitors, perhaps even cured of their stage four lung cancer with immunotherapy, there still has to be a lot of work with regards to immunotherapy and how to get it to work for patients with EGFR disease.

There's probably a fair amount of promise with incorporating anti-VEGF agents with immunotherapy in the EGFR space but I'll also say the data on this from prior trials have been a bit mixed. I mean, to that point, we actually lead an investigator initiated clinical trial here at Fox Chase Cancer Center looking at a combination of chemotherapy plus immunotherapy plus a VEGF agent bevacizumab (Avastin; Genentech) in patients with the EGFR disease that is nearly done accrual at this point. So hopefully that'll provide some additional answers.

But then I think there's also a number of kinds of exciting preclinical work as well in this space. There's work that we're doing here at Fox Chase looking at the role of estrogen suppression in combination with immunotherapy and we're testing that combination in an EGFR mutant mouse model and we're hopeful that this may kind of yield promising preclinical data that may translate to benefit patients seen in the clinic.

So, like I said, immunotherapy checkpoint inhibitors really has been a game changer for our field of non-small-cell lung cancer. However, the fact that we've not been able to get such agents as it currently stands to benefit patients with EGFR disease is really one of our greatest current challenges in this space.