Navigating Perioperative Immunotherapy Decisions in Lung Cancer Care: Jonathan Thompson, MD, MS

At a recent Institute for Value-Based Medicine® event, Jonathan Thompson, MD, MS, a hematology/medical oncology specialist and associate professor at Froedtert and the Medical College of Wisconsin in Milwaukee, highlighted that patients who achieve a pathologic complete response (pCR) after neoadjuvant chemo-immunotherapy often derive little additional benefit from adjuvant immunotherapy, whereas those with incomplete responses face higher recurrence and mortality risks and may benefit from an added year of adjuvant treatment. However, Thompson emphasized the lack of prospective randomized trials directly comparing neoadjuvant-only vs perioperative (ie, neoadjuvant plus adjuvant) strategies, noting that further evidence is needed to guide decision-making.

Regarding immune-related adverse events (IRAEs) in the adjuvant setting, Thompson explained that management depends on severity: mild toxicities may be managed through continued therapy, while severe toxicities typically warrant discontinuation, especially given the curative intent and the risks of long-term morbidity. He noted that some evidence from metastatic non–small cell lung cancer (NSCLC) trials suggest patients who discontinue immunotherapy due to toxicity may still achieve strong outcomes, potentially reflecting heightened immune activation. Until more robust perioperative data are available, patient-centered decision-making remains essential in balancing efficacy and safety, according to Thompson.

This is the fourth part of a 6-part interview series with Thompson.

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

Transcript

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

The benefits of neoadjuvant and adjuvant immunotherapy for early-stage patients, we do see those who have the best overall response to neoadjuvant chemo-immunotherapy or those with that pathologic complete response, or path CR, probably don't have much benefit to additional adjuvant immunotherapy; they're already destined to have a very good survival outcome.

However, the challenging situations are those patients who have less than a complete pathologic response to neoadjuvant chemo and immunotherapy. There we see clear signals that their recurrence risk, their risk of mortality from lung cancer is much higher than those who have the path CR. Those are the patients where we tend to use that additional 1 year of adjuvant immunotherapy after surgery.

Again, we don't have compelling prospective randomized clinical trials that have compared the neoadjuvant only to the neoadjuvant followed by adjuvant immunotherapy. Hopefully, at some point in the future, we'll have some answers from clinical trials that'll help better inform that decision-making. As of right now, we don't.

How confident are you in stopping therapy in the adjuvant setting should immune-related adverse events occur, and what data support such decisions?

If an immune-related adverse event occurs in the adjuvant setting to immunotherapy, I always look at what type of IRAE are they experiencing and how severe is it? If it's a mild toxicity, like a skin rash that we can easily control with a topical steroid, there we’re very inclined to push through the toxicity. On the other hand, if a severe toxicity, like a high-grade colitis or pneumonitis, there I am much more reluctant to rechallenge with the checkpoint inhibitor in the adjuvant setting, keeping in mind that these are patients where the goal is cure, where we may have already achieved that with the surgery, and then the systemic therapy they've already received. We have a longer runway with those patients, where we worry about contributing to long-term morbidity from our drugs.

Generally, if I encounter a severe toxicity to immunotherapy in the adjuvant setting, I'll stop it, with the patient playing a role in the decision-making. In terms of what those patients' outcomes look like compared to those who just complete the full perioperative immunotherapy approach, I think we don't have extremely solid data from the perioperative clinical trials so far. We could potentially extrapolate from the data we have from the metastatic immunotherapy trials in the non–small cell lung cancer setting.

There, we see actually that sometimes the patients who have these toxicities that require discontinuation of therapy actually sometimes do better than the patients who don't have those toxicities. Potentially, that may be because their immune systems are more engaged by the immunotherapy, not only driving a great cancer response but also causing toxicity. I think we can, when counseling patients in the adjuvant setting, if we're coming off of immunotherapy, I do commonly mention that maybe this is just a sign that their immune system is really engaged already by the immunotherapy. But, again, we need better long-term data and readout from these perioperative studies, too.