Chemotherapy Plus Immuno-Oncology for Lung Cancer With High PD-L1 Expression

Patrick Forde, MD, Johns Hopkins Medical Institute, Baltimore, MD, makes the case for chemotherapy plus immuno-oncology (IO) as the best treatment option for patients with lung cancer and PD-L1 expression of 50% or greater, a position he defended at the Great Debates and Updates in Lung Cancer conference in Chicago, IL.

Transcript

I'm Dr. Patrick Forde from Johns Hopkins. Today I was debating with Dr Eddie Garon [University of California, Los Angeles] about the treatment for patients who have PD-L1-high advanced non-small cell lung cancer. This is a population which makes up about 30% of patients we see with lung cancer. We have 2 main potential treatments for these patients. One of them is chemotherapy with anti-PD-1 or PD-L1 immunotherapy, or PD-1 or PD-L1 monotherapy. We don't have direct comparative trials. We have trials comparing chemotherapy and immuno-oncology (IO) with chemotherapy, and we have trials comparing IO with chemotherapy. My side of the debate was in favor of chemotherapy-IO, and this is also my preferred choice for most patients in this population. The reasons I put forward are that patients with advanced non-small cell lung cancer are often quite symptomatic, and we get higher response rates with chemotherapy-IO upfront, and faster responses can relieve their symptoms.

There’s also some concern that about 30% to 40% of patients don't receive any further therapy after their first treatment for lung cancer. That makes an argument that we should try and treat those patients with the most effective therapy upfront. That is, at least in terms of response, chemotherapy with immunotherapy. The other thing supporting this argument was that when you look at the curves of progression-free survival, in terms of how long it takes before their tumor starts to grow again on therapy, those curves overlap between IO monotherapy and chemotherapy. That suggests that some patients don't benefit from IO monotherapy, even if they have PD-L1-high tumors.

Who are those patients? Well, the patients I specifically think of chemotherapy-IO for are those who are non-smokers, because we've seen in multiple studies now that they may not benefit as much from IO monotherapy. Also, those patients who have characteristics in their tumor which may predict resistance to immunotherapy. Those are things like STK11 mutations, KEAP1 mutations, and as I mentioned earlier, those patients who are most symptomatic from their cancer. Those are the patients. Even though their tumor may be PD-L1-high, I think we still have to think of the incorporation of chemotherapy for that population.

Source:

Forde P. “How to Handle PD-L1 >50% - Chemotherapy Plus Immuno-Oncology.” Presented at Great Debates & Updates in Lung Cancers. May 4-6, 2023; Chicago, IL