Naiyer Rizvi, MD: What about the group with PD-L1 [programmed death-ligand 1] expression of 1% to 49%? I think it's a tough area. I think we look at the KEYNOTE-042 data, which was positive in overall survival in the more than 1% group. But the benefit in the 1% to 49% group was significantly more modest, I guess. Jacob, do you want to talk to me about the 1% to 49% group?

Jacob Sands, MD: The single-agent pembro [pembrolizumab] data in that group were not that compelling to me, quite frankly. I would prefer combination chemo [chemotherapy] plus pembrolizumab. Chemotherapy is generally reliable, and when we're talking about non-squamous, non—small cell lung cancer, carbo [carboplatin]/pemetrexed is pretty well tolerated as well. So I don't have a lot of hesitations about that except for in particularly unfit patients.

So, carbo/pem/pembro [carboplatin, pemetrexed, pembrolizumab] I think tends to be a fairly well tolerated regimen, and is fairly reliable. That's what I choose in that patient population. Now, there are some people where they really are borderline in their functional status, or some people where the risk of chemotherapy is maybe a little bit more. And in those patients with discussion, or patients who refuse chemotherapy altogether, then I don't hesitate about using pembrolizumab alone, although I do prefer using chemotherapy with it. The checkpoint inhibitors I see as like swinging for the fences. You really are swinging for a home run. And for many patients, as PD-L1 expression goes down, the likelihood of hitting that home run goes down. But when it's effective, it can really be amazingly effective. And so if there are patients where not giving chemotherapy makes sense because of functional status or they don't want it, then I'm OK with pembrolizumab. But I do prefer the combination.

Naiyer Rizvi, MD: Josh, have you treated any patients with 1% to 49% with pembrolizumab monotherapy? I bet the answer is yes.

Joshua Bauml, MD: I have not. Basically, my take is that if somebody is so sick that I don't think that I can give them carboplatin, pemetrexed, pembrolizumab, then I really want to think about whether I should be treating this person at all. And I will talk to them; if they have concerns or refuse chemotherapy, I find that's often an education question more than anything else. It's a belief about what chemotherapy is and what it is not. And that's not really consistent with modern day. They'll say, “Oh, I'm going to be up vomiting all night, and I'm going to be suffering in these horrible ways” Well, with modern supportive measures, that's not what most of our patients experience, and so I'll talk with patients about it rather extensively. I haven't done it. I really don't want to, but we'll see.

Naiyer Rizvi, MD: Leora?

Leora Horn, MD, MSc: I have. There are some patients in their late 70s and 80s who are like, “I want to maintain my independence and my quality of life.” I don't think that it's unreasonable, and so the discussion is that pembrolizumab alone in that group of patients is not worse than chemotherapy. It's not necessarily better, but it's not worse when you look at the long-term survival. We just don't have the direct third arm, which all of those trials were missing, of chemotherapy and pembrolizumab. I've had some patients, most of them, Josh is right, patients are either 5%, 30%, 50%, or 80% PD-L1 expression. That seems where they fall, and most of these patients have been 30%. A few of them have responded, and if they can maintain their independence, drive to their doctors’ appointments, and keep doing what they want to do, I don't think it's an unreasonable consideration.

Joshua Bauml, MD: I'll tell you what I have done, and this may connect a bit of concern toward Tim, is I had a patient who is an 85-year-old man who had locally advanced disease and absolutely refused chemoradiotherapy. His PD-L1 was 60%. He's now 2 and a half years receiving pembrolizumab. He said, “Look, I know I’m not going to be cured with this approach, but I'm going to have good quality of life.” And that's something I have done. But we spoke at length about the fact that this is a palliative approach. This is not a curative intent approach.

Naiyer Rizvi, MD: Right. I tend to agree with everyone. I think that factoring in age as well as the volume of disease, if they have limited volume disease and are elderly, and I think we can wait for the chemotherapy for 2 or 3 cycles, then I would do that for the 1% to 49%, but my expectations are low.

Transcript Edited for Clarity