NSCLC: Selecting Therapy Based on PD-L1 Status and Staging


A brief review of how treatment may be selected for a patient with NSCLC based on their PD-L1 expression and disease staging.


Charu Aggarwal, MD, MPH: I wanted to ask a provocative question here, if you knew a priori [that you had] 2 patients with clinical stage 3a disease and were deciding on treatment strategies. One has PD-L1 negative disease and one has PD-L1 positive disease [of,] let’s assume, greater than 50%: Are you more likely to choose neoadjuvant chemo[therapy]-IO [immune-oncology] in your PD-L1–negative patient, thinking that you may not be able to come in with adjuvant IO? Might that be a treatment approach in the future considering the same stage?

Heather Wakelee, MD, FASCO: That is an excellent question. I think one of the really important things to emphasize is that with the CheckMate 816 [trial (NCT02998528)]with neoadjuvant nivolumab, it was with the chemo and the adjuvant trials were after the chemo. We know from the metastatic disease setting that when we combine chemo and immune therapy, it works better than either alone. Even though PD-L1 is important, it’s less important there and we see this with CheckMate 816 also. When you look at the subset based on PD-L1 expression, all patients seem to benefit, but there is more benefit with higher PD-L1 levels. So if I have a patient who has no PD-1 expression, I’m going to look at the data from the IMpower010 [trial (NCT02486718)]

that show adjuvant immune therapy wasn’t particularly helpful there when you give it alone versus with chemo.

Then I’m going to look at CheckMate 816 and say well, I can combine immune therapy and chemo together. There, the PD-L1 isn’t as important, so maybe that’s a better approach for this patient. For stage 3a, that’s where I think we’re more inclined toward neoadjuvant chemo anyway. So yes, if I have a patient at stage 3a with no PD-L1 expression, I’m going to be more inclined toward chemo/nivolumab in the neoadjuvant setting than I am toward an adjuvant immune therapy approach. However, the ANVIL [NCT02595944]study had the chemo plus pembrolizumab. I don’t think it’s quite open yet but it’s moving in that direction. Once we have adjuvant chemo plus IO, then we can look at what’s adjuvant plus adjuvant chemo plus IO versus neoadjuvant chemo plus IO, and decide which of those might be better. I think the questions get a little bit endless but for right now, with stage 3a and no PD-L1 expression, I would lean more toward neoadjuvant chemo-IO.

Charu Aggarwal, MD, MPH: That’s great. This has been a terrific discussion on management of early-stage non–small cell lung cancer in the absence of a biomarker.

Transcript edited for clarity

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