This transcript has been edited for clarity.
Hello. It's Mark Kris from Memorial Sloan Kettering, speaking today about perioperative therapy and the tremendous opportunity we have now as medical oncologists as part of a multidisciplinary team to improve the survival and, more importantly, the curability of people with locally advanced lung cancer.
In the July 13, 2023, issue of The New England Journal of Medicine , data on the use of osimertinib in the adjuvant setting were published, and there was a focus on survival. While many were looking at that survival improvement — and there was a clear improvement there — I was into the weeds in the supplemental data.
What I could see in there was very clear proof of the usefulness of chemotherapy with osimertinib. If you gave chemotherapy with osimertinib, there was a clear improvement over osimertinib alone. The benefit of chemotherapy was there, comparing either patients with placebo or osimertinib, demonstrating that by giving chemotherapy, you further improve survival.
I know there's a huge temptation to say, "Well, you're going to have good results with osimertinib; it's EGFR-mutant disease, why give chemotherapy?" But clearly the chemotherapy improves outcomes. Please remember here that, yes, chemotherapy is difficult and it disrupts lifestyle absolutely. We're talking about cure here. By increasing the chance of cure, it really makes sense to recommend chemotherapy to every single patient.
The other thing I want to remind you of is the tremendous advantage of osimertinib in giving people the potential to be cured. Please remember the initial publication where they had very clear benefits in progression-free survival. There was a 40% or more improvement in 3-year progression-free survival by adding osimertinib. It says to me that you've increased the chance of giving somebody a cure by 40% by giving osimertinib. We really need to do that.
The other issue that's come up is the growing evidence of the benefits of neoadjuvant therapy. There are now four large, randomized trials where neoadjuvant checkpoint inhibitor plus chemotherapy was better than chemotherapy alone. I think it's pretty conclusive that, in terms of progression-free survival and pathologic complete response, there's benefit there. That is important.
The other thing that's important in these papers is that they basically excluded patients who had EGFR and ALK. What that says is that if you think you want to give a patient adjuvant therapy, you need to know if they have EGFR or ALK and you need to know that right at diagnosis. It's important to get that information so you can make the best choice for your patient, but you're also going to now know that a patient has EGFR-mutant disease upfront. What are you going to do?
Well, I think today's guidelines would say that you could give them standard chemotherapy, followed by surgery, followed by osimertinib. You could take the patient right to surgery and give chemotherapy and then osimertinib.
But extrapolating from the data on giving a checkpoint inhibitor with chemotherapy and knowing about the safety of chemotherapy with osimertinib, I think we're going to see more and more that you're going to want to give chemotherapy with osimertinib upfront. I know that's a little bit ahead of the curve, but it can be done safely, there's good evidence of that, and it makes sense.
Also, it's much harder to give the chemotherapy after surgery. One thing that's clear from all the neoadjuvant trials is that it's easier to give chemotherapy then.
We have a tremendous opportunity as medical oncologists to make an impact on our patients with locoregional disease. The era of systemic therapy, or at least the consideration of systemic therapy for anybody with early-stage lung cancer, is here.
I urge you to put together multidisciplinary teams and see what you can do to make multidisciplinary care a reality for every single patient with locally advanced disease. We can clearly improve outcomes. The data are there now, and I think as more data come in, we're going to be even more assured that we can change things.
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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Cite this: Case for Combining Chemo and Osimertinib in NSCLC - Medscape - Nov 01, 2023.
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