Mark Socinski, MD: I’ll ask Gilberto to give us a brief overview of I/O [immuno-oncology] options in this setting and explain the impact that it’s had on the standard of care. It’s changed everything in the first-line setting.

Gilberto Lopes, MD: Absolutely. When we look back 10 years, when we had median survivals of less than 10 months without chemotherapy, and 10 to 12 months with chemotherapy, without a doubt that we have much better situation today. That started with the target agents EGFR, ALK, and so on. But for the majority of patients we still don’t have target agents. Chemotherapy plus immunotherapy has become the standard of care for patients that don’t have a PD-L1 equal to or greater than 50%. In that specific subpopulation, we now have the option of using immunotherapy alone, and we’ve already alluded to the 3 approved drugs: imatinib [Gleevec], atezolizumab [Tecentriq], and pembrolizumab [Keytruda]. As you mentioned, Mark, I’d be very comfortable using any of those. I tend to use pembrolizumab more than anything else in that situation, because we’ve been using it from the beginning and it was the first agent to be approved in that specific subpopulation. We also have questions in terms of using pembrolizumab in the earlier settings, but I’m not going to discuss that too much. We now have IMpower110 trial data suggesting that there’s a benefit, at least in disease-free survival, in patients who are PD-L1 1% or more and especially 50% or more. I’d be very comfortable using atezolizumab for patients in the advanced setting, who express PD-L1 at 50% or greater. I’m waiting for the approval to start pushing for patients with 1% or greater. I don’t think I’ll use it for patients that don’t express any PD-L1.

Mark Socinski, MD: It’s important for our audience to know, and it’s something that all of us probably see on a weekly basis in our practices, but we never saw these patients who would have these deep responses that would last for years. I’m sure all of us can tell stories, and some people that I thought didn’t have a very good prognosis and were quite sick with I/O therapy—either alone or with chemotherapy—get through 2 years. Every time I see them in the third year to get a scan every 3 months, I’m keeping my fingers crossed, but things are holding up and people are doing well. We didn’t see that before.

Gilberto Lopes, MD: Not at all.

Jack West, MD: What’s remarkable is a few things: No. 1, we have a bunch of targets and therapies for nonsmokers with an adenocarcinoma, but we had 10, 15 years without very much to suggest for people who didn’t fit that demographic. Some patients have a driver mutation with a smoking history, and even somewhat squamous, but not most. Too many of our breakthroughs are great news for the same sliver of patients, but this is something that’s applicable to a big, broad swath of patients. If you’re practicing in Kentucky, you see a ton of patients who can benefit from these therapies, whereas you don’t see that many Asian nonsmokers, as we do in California or up and down the West Coast. That’s great, and it’s common, in addition to the 28% to 30% of patients with high PD-L1, and immunotherapy combined with chemotherapy benefits other patients too. You’re talking about a big population of patients who have the potential to redefine what we thought was possible for metastatic cancer and get in a realm similar to what we’ve seen with targeted therapies that blew our minds 10 to 15 years ago.

Mark Socinski, MD: I love targeted therapies—don’t get me wrong, they’re highly effective—but I don’t view them necessarily as curative. But I’m beginning to think that we might be curing some of these patients who we were all trained to believe weren’t curable. It’s very different. Dr Barzi, I want to invite you back into the conversation and get your perspective on the general concept of immuno-oncology in GI [gastrointestinal] tumors. Where do you use it? What are your thoughts? Has it been as impactful as you hear the lung cancer crowd endorse its impactfulness? What are your thoughts?

Afsaneh Barzi, MD, PhD: Unfortunately, it hasn’t been as impactful in GI as it’s been in lung cancer—with the exception of HCC [hepatocellular carcinoma] or liver cancers—and it probably has changed its standard of care. In other parts of GI, not so much, but in MSI [microsatellite instability]–high site-agnostic cancer—remember, the approval for pembrolizumab for MSI-high is site agnostic—that’s the meaning of tumor biology. It’s the tumor biology that drives the outcome, regardless of where the site is. I always say that’s as close to a cure as we get. For these are patients who I’ve treated, when I get to 2 years, I stop their treatment. You still see things on their imaging, but they do fine and I don’t think we’ve seen, in oncology, at least in my area, the term of cure without surgery. Now we’re seeing that. That’s remarkable, and we shouldn’t forget about it. When you look at the immuno-oncology in other fields, immuno-oncology has a footstep in every cancer—solid or liquid—that we look at. Many trials have established their efficacy, many with guidelines. Even in small diseases—rare diseases by guideline case studies, case cohorts, or smaller studies—there isn’t an area of oncology that you look at and can’t see a footstep of some form of immuno-oncology.

Transcript edited for clarity.