Suresh S. Ramalingam, MD, FASCO: When we look at immune checkpoint inhibition in the frontline treatment of lung cancer, do you see any differences in efficacy with these agents between patients who are squamous versus those who are nonsquamous?

Byoung Chul Cho, MD, PhD: As a single agent?

Suresh S. Ramalingam, MD, FASCO: Or combination with chemotherapy. I obviously want you to review some of the combination data in squamous cell with our audience as we address this issue.

Byoung Chul Cho, MD, PhD: I don’t see difference of I/O [immuno-oncology] single agent or I/O combination according to histology subtype. For I/O and chemotherapy combination, the KEYNOTE-407 study demonstrated a significant improvement of OS [overall survival], a significant improvement of PFS [progression-free survival], and objective response rate. This combination, pembrolizumab and cytotoxic chemotherapy, has been the standard of care in first-line lung adenocarcinoma as well as lung squamous cell carcinoma, regardless of PD-L1 [programmed death-ligand 1] expression. I think this makes a paradigm change in our routine practice, especially in treatment-naїve advanced-stage NSCLC [non—small cell lung cancer].

Suresh S. Ramalingam, MD, FASCO: As we think about agents beyond pembrolizumab, Johan, we saw the results from ATEZO [atezolizumab] plus CARBO [carboplatin]—nab-paclitaxel at the International Association for the Study of Lung Cancer WCLC [World Conference on Lung Cancer] meeting recently. There was a PFS benefit. Talk about the survival data from the trial.

Johan F. Vansteenkiste, MD, PhD: Yes. There was a PFS benefit previously reported. The overall survival data from that trial point was at the superiority of the combination of atezolizumab and chemotherapy in patients with very high PD-L1 expression. The biomarker used in these types of trials is the combined tumor cell and immune cell score by the SP142 antibody, which perhaps is not the best antibody. But those who had a 3, immune cells or tumor cells, they had a significant benefit in overall survival when you added atezolizumab to combination chemotherapy. Those who were in 2 did not achieve a significant overall survival benefit, and then because of that, there was a hierarchy of testing in that trial. Because of that, the ones that came at the 1 were no longer tested. It’s the PD-L1—high patients who seemed to derive benefit when you add the atezolizumab to the backbone of carboplatin and nab-paclitaxel.

Suresh S. Ramalingam, MD, FASCO: At this point, for PD-L1—positive patients, regardless if they are low or high positive, we can’t just say, “Use chemo [chemotherapy] plus ATEZO for those patients, probably chemo plus PEMBRO [pembrolizumab].” If you have the highest positivity, that could be a consideration for using chemo plus ATEZO.

Johan F. Vansteenkiste, MD, PhD: Yes.

Pasi A. Jänne, MD, PhD: Or single-agent PEMBRO.

Suresh S. Ramalingam, MD, FASCO: Or single-agent PEMBRO.

Pasi A. Jänne, MD, PhD: Yeah.

Suresh S. Ramalingam, MD, FASCO: Let me touch on that, Pasi. You bring up single-agent PEMBRO. Whom do you give single-agent PEMBRO to in your practice now?

Pasi A. Jänne, MD, PhD: Yeah, I think it’s an interesting point, because if you’re greater than 50% PD-L1, you can give single-agent PEMBRO or you can give PEMBRO and chemotherapy. I think there is some subjective decision making that goes into that. For example, somebody who really needs a response—meaning that their disease is central, they’re about to block off airway, things like that—I think you want to give both to give the maximum likelihood of having a response. Somebody who has low disease burden, an elderly patient, I think I would be more inclined to start with a single-agent PEMBRO as opposed to combination chemotherapy to avoid toxicity and not being so urgent in terms of the disease. There is some subjective decision making that goes on there, even though both are technically options.

Johan F. Vansteenkiste, MD, PhD: That is also related to the fact we have quite a lot of trials now comparing immunotherapy and chemotherapy, usually in PD-1 [programmed cell death protein 1]—high disease. We have trials comparing chemo plus immuno [immunotherapy] versus chemo alone, but we don’t have the trials comparing immuno alone versus chemo plus immuno. Therefore, of course, there is a certain subjective factor in it.

Suresh S. Ramalingam, MD, FASCO: Johan, to that point, I’m happy to say that in the US, there is a cooperative group trial led by ECOG [Eastern Cooperative Oncology Group]—ACRIN [American College of Radiology Imaging Network] that compares chemoimmunotherapy versus immunotherapy followed by chemotherapy at the time of progression, which will help us understand the sequencing question.

Johan F. Vansteenkiste, MD, PhD: Very important, yes.

Pasi A. Jänne, MD, PhD: That brings up another interesting question, and I assume that’s in the greater-than-50% patient population?

Suresh S. Ramalingam, MD, FASCO: That includes both greater-than-1% and the greater-than-50% populations.

Pasi A. Jänne, MD, PhD: Right. Because what happens if somebody starts with I/O and doesn’t respond? How well does chemotherapy do there, or do you use chemo and I/O in that situation, right? I think these are areas that we lack a little in knowledge.

Suresh S. Ramalingam, MD, FASCO: This trial has 3 arms to answer exactly the issues that you bring up.

Pasi A. Jänne, MD, PhD: Excellent.

Suresh S. Ramalingam, MD, FASCO: We look forward eagerly to those results.

Transcript Edited for Clarity