Where Are Checkpoint Inhibitors Standard of Care for NSCLC?

Mark G. Kris, MD


December 09, 2022

This transcript has been edited for clarity.

This is Mark Kris from Memorial Sloan Kettering. A few months ago, I was asked by Wylie Hosmer, a medical oncologist from Hartford, Connecticut, to speak to his disease management team group about issues in the treatment of early-stage patients with non–small cell lung cancers.

It's an area that is very vibrant, there are many new drugs available, and there are many questions. The tumor board at Hartford and tumor boards everywhere in the United States are having issues dealing with this. Wiley asked me three questions to answer for his tumor board, and what I'd like to do in the next three talks is share his questions and my answers for them.

The first question was, should we consider checkpoint inhibitors as standard of care for patients in the adjuvant and neoadjuvant setting? My answer to that is yes. We now have two FDA-approved therapies in this setting.

The first thing to remember, though, is a word about adjuvant and neoadjuvant therapy. Please remember that unlike patients with advanced disease, the goal of therapy here is cure. We need to pull out all the stops we can to increase the chance of cure for our patients here. As we make therapeutic decisions, please remember that this is not the same as a patient with more advanced disease, where our goals are more limited. Here, the goal is cure and we have to keep our mind on that.

There are two approvals. The first one was for atezolizumab. Atezolizumab was approved based on a clinical trial that showed a dramatic improvement in disease-free survival for patients with stages II to IIIA lung cancers that had PD-L1 expression and had received chemotherapy with a cisplatin-based regimen. These patients were randomized to atezolizumab or not.

Importantly, when you look at the data, there was very little improvement in patients who had EGFR mutations or ALK arrangements. I would urge that patients with driver-positive disease are not candidates in that setting, so we need to look to another way to treat these people.

What about the neoadjuvant setting? Recently, there was an approval for nivolumab in combination with platinum-based chemotherapy for patients with any nodal disease, N1 or N2, and tumors greater than 4 cm in size. That would be stages IB to IIIA. In that approval, there was no mention about the PD-L1 expression. In the atezolizumab trial, it needed to be at least 1%, but here there was no mention for that. In the approval, it said specifically that these patients should not have EGFR mutations or ALK rearrangements.

Moving forward, I think both neoadjuvant nivolumab in combination with cisplatin- or platinum-based chemotherapy is appropriate care for patients who are candidates for neoadjuvant therapy. For other patients in this setting who have PD-L1 expression and stage II to IIIA disease, they would be candidates for adjuvant atezolizumab after surgery and after the completion of platinum-based chemotherapy.

Which one is better? That's going to be the topic of the next talk.

We have two FDA-approved agents. I believe they do represent the standard of care. They're appropriate for both the adjuvant and neoadjuvant setting, and they're most appropriate for patients who have PD-L1 expression and do not have ALK rearrangements or mutations in EGFR.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. His research interests include targeted therapies for lung cancer, multimodality therapy, the development of new anticancer drugs, and symptom management with a focus on preventing emesis.

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