COMMENTARY

In Early-Stage NSCLC, Give Nivolumab Before or After Surgery?

Mark G. Kris, MD

Disclosures

December 09, 2022

This transcript has been edited for clarity.

Hello. It's Mark Kris, continuing our discussion on advances in the treatment of patients with early-stage lung cancers.

In an earlier discussion, we talked about the appropriateness of either neoadjuvant nivolumab with chemotherapy followed by surgery or surgery followed by cisplatin-based chemotherapy and then followed by nivolumab.

I think both regimens are FDA approved. They require expression of PD-L1, I would say, though that is not explicitly stated in the nivolumab approval. They would be best for patients who do not have ALK rearrangements or EGFR mutations. Both are important advances in therapies and can enhance cure.

Which do you choose: adjuvant or neoadjuvant?

I'm going to make the case that neoadjuvant is the preferred approach. Why is that? Number one, for these patients, what is the risk to their life? It is metastatic cancer. In that setting, it makes more sense to give them an agent targeting metastatic cancer as quickly as possible, and that would be the neoadjuvant setting.

The second advantage of the neoadjuvant approach is that you can assess the actual benefit of chemotherapy in these patients by monitoring their scans and their progress so you can tell if that therapy is working. It can be discontinued or changed if ineffective, and there are data to support that. It also gives you a hint about the appropriateness of that therapy were you to use it in the adjuvant setting, so that's another advantage.

In general, neoadjuvant therapies are better tolerated, and it also gives you time to learn more about the person you're taking care of, including comorbid illnesses or, unfortunately, often undetected metastatic disease. In addition, it gives you the opportunity by examining the resection specimen to estimate the benefit of that regimen. It's been shown in the trials that have been done to date that pathologic response, particularly pathologic complete response, is a potent predictor for that patient of disease-free and overall survival. That's an important piece of information in taking care of that patient.

The second thing is, if you're in the drug development business, it gives you the opportunity in just a few months to know if a drug has potential usefulness long term based on its success. The data to date support that, and more data are being amassed to try to prove it more definitively.

There are advantages to adjuvant therapy as well. The first is that the patients there are precisely staged. Please remember that staging is surgical staging, which can only be done at surgery. It also gives you ample tissue to test. That's not always the case with the diagnostic specimens at the beginning of treatment, but you have tissue and time as the patient rehabilitates from surgery.

The third thing that I think is an advantage for the adjuvant approach is with targeted therapies for patients with EGFR mutations. Today, that's the approved category, and I think other targeted therapies will be shown to be beneficial in the future. There, I think it makes most sense to continue those for longer periods of time and it makes the most sense to do that in the adjuvant setting. Our model here are gastrointestinal stromal tumors (GISTs), and in general, the longer imatinib was continued as adjuvant therapy for GISTs, the better the results.

Adjuvant and neoadjuvant approaches both are appropriate. I would favor neoadjuvant for the reasons that I have described. We now have both available to us for patients that are operable, resectable, have no mutations in EGFR or ALK rearrangements, and have some expression of PD-L1.

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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