Clinical Considerations for Immunotherapy Sequencing in NSCLC: Lauren Antrim, MD

At a recent Institute for Value-Based Medicine® event, Lauren Antrim, MD, a medical oncologist at City of Hope Cancer Center Duarte in California, discussed the evolving role of immunotherapy in non–small cell lung cancer (NSCLC). Antrim highlighted ongoing uncertainties around optimal treatment duration in both advanced and perioperative settings, as well as the clinical decision-making challenges involved in balancing neoadjuvant, adjuvant, and perioperative approaches. Antrim also underscored the importance of multidisciplinary collaboration, emerging evidence from adaptive trials, and the potential for circulating tumor DNA (ctDNA) to help guide individualized immunotherapy strategies.

This transcript was lightly edited; captions were auto-generated.

Transcript

Immunotherapy has significantly reshaped the NSCLC treatment landscape. In both advanced and perioperative settings, what are the key considerations for determining optimal treatment duration?

I think there's a lot of questions still in terms of an ideal timing of immunotherapy in both the perioperative or adjuvant vs metastatic setting. With something like giving neoadjuvant immunotherapy or neoadjuvant chemo immunotherapy, which is more often given, if at resection, they have such an amazing pathological complete response, a lot of time, physicians will think, “Hey, maybe we don't need to give the adjuvant portion because there's such low rates of recurrence,” but that's not necessarily guideline directed. We need more trials in order to identify if that actually is the best kind of way to evaluate. There isn't really any head-to-head comparisons of perioperative vs just neoadjuvant or neoadjuvant vs adjuvant. Those trials definitely need to be done and hopefully are being done somewhere right now.

In terms of the metastatic setting, historically, we've gone with the 2-year rule, because that's what was done in the studies, and some of the evidence has shown that 1 year does have less benefit than 2 years. But the question is: Should we continue after 2 years? Are there some people that would be fine after 1 year? We actually got an amazing grant recently to fund this adaptive bioimmuno trial, which is actually going to be looking at these things. Is 1 year with ctDNA being cleared for a significant period of time? Are those patients going to benefit? There are multiple different arms in this. Some patients could be potentially getting less immunotherapy. Some patients might be getting prolonged immunotherapy based on their ctDNA response.

In early-stage disease, what do we know about the relative benefit of neoadjuvant vs adjuvant immunotherapy, and how does that inform treatment selection?

In early-stage disease, if we're talking about stage II to IIIA, there is the option of doing resection first, followed by adjuvant chemoimmunotherapy in patients that are not with EGFR or ALK mutations, vs doing a perioperative approach with chemoimmunotherapy vs doing a neoadjuvant approach with chemoimmunotherapy, all with EGFR and ALK usually excluded from this. I think the general consensus, or expert consensus, is that if a patient is stage IIIA and resectable, that we do want to downstage by doing neoadjuvant chemoimmunotherapy in those patients. There's actually an amazing article that I recently read from Spicer at al.¹ It's from [the International Association for the Study of Lung Cancer] from last year, and it's expert consensus recommendations. They have 19 recommendations, and they really overwhelmingly agreed upon that in that stage IIIA setting, if there's the option to downstage, it should be done. If it's in the stage II setting, there was a lot more not consensus on that, because a lot of patients, if they have an amazing response to this, and they were already pretty resectable, you're risking the side effects of chemoimmunotherapy, potentially causing resection to be canceled. It's more of risks and benefits. Ultimately, this is going to need to be brought to tumor board, and a multidisciplinary discussion is going to need to be done for any of these patients, really, in early stage.

Reference

Spicer JD, Cascone T, Wynes MW, et al. Neoadjuvant and adjuvant treatments for early stage resectable NSCLC: consensus recommendations from the International Association for the Study of Lung Cancer. J Thorac Oncol. 2024;19(10):1373-1414. doi:10.1016/j.jtho.2024.06.010