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Trials Affirm Value of Immunotherapy in Resectable NSCLC

— James Stevenson, MD, discusses the NADIM II and IMpower010 findings

MedpageToday

Two studies shed light on the impact of immunotherapy on survival in patients with resectable non-small cell lung cancer (NSCLC), in the adjuvant and neoadjuvant settings. The findings from both the NADIM II and IMpower010 trials were presented at the recent World Conference on Lung Cancer (WCLC).

In this exclusive ڴŮ video, , vice chairman of the Department of Hematology and Medical Oncology at Cleveland Clinic's Taussig Cancer Institute in Ohio, analyzes the studies.

Following is a transcript of his remarks:

Today, I'd like to review a couple of updates of studies that we just heard about at the World Conference on Lung Cancer that just happened in Vienna, Austria. These two studies were updates on use of perioperative immunotherapy in early stage non-small cell lung cancer regarding regimens that had already been approved for use, but based on some recurrence-free survival data. And these were some of the first hints of overall survival data that we heard that were presented at the World Conference on Lung Cancer.

The first study, the IMpower010 trial, which looked at the use of adjuvant atezolizumab [Tecentriq] versus best supportive care following adjuvant chemotherapy in early stage non-small cell lung cancer did show a trend in the improvement in overall survival for the entire group. When we look at the stage II-IIIa PD-L1 positive patients, when the PD-L1 greater or equal to 50% subgroup was looked at, the overall survival benefit was even greater, with an impressive hazard ratio of 0.42. Not surprisingly, given what we know about PD-L1 high patients. Still kind of early data in terms of the survival follow-up for that trial, but these were the first reports that we heard again, looking positive, especially in the PD-L1 high subgroup. So I think it affirms what we're doing in the adjuvant setting for the PD-L1 positive patients with offering them atezolizumab after adjuvant chemotherapy. Whether further follow-up will change some of that practice to focus on maybe a high PD-L1 subgroup remains to be seen. So that'll be the next interesting bit of data that we get. So practice affirming in my mind.

But then we also heard an update on the NADIM II trial, which was a smaller randomized study looking at neoadjuvant nivolumab [Opdivo] plus chemotherapy in stage IIIA-B non-small cell lung cancer. So three cycles of chemoimmunotherapy prior to surgery, and actually the NADIM II trial included an option to use adjuvant nivolumab for 6 months after surgery. And we did hear, previously heard positive results about complete response rates in that trial, and now we hear some really promising overall survival update from that trial with a 20% improvement in 2-year survival in the patients who got chemoimmunotherapy, which is up over 85% two-year survival for the whole subgroup. Again, these are stage III patients. So even worse prognosis when we look at this stage compared to stage IB or II.

So it looks like again, those data affirm what we heard about previously with NADIM II as well as the NADIM trial. And of course also with the Checkmate-816 trial, which led to the approval of nivolumab plus chemotherapy, given in a neoadjuvant setting for stage IB-IIIA non-small cell lung cancer, regardless of PD-L1 status.

So, what this means is, again, it affirms current practice that neoadjuvant chemoimmunotherapy is a good option for patients, especially when we look at PD-L1 negative patients. Because in the adjuvant setting, there is no option for immunotherapy in PD-L1 negative patients.

So I think we need to take the opportunity to look at PD-L1 status very early on when we're working up early stage lung cancer patients, that if it is a PD-L1 negative patient, then that definitely would, I think, push us more to using neoadjuvant therapy incorporating nivolumab, so that they do have a potential benefit there that they could achieve with immunotherapy.

So immunotherapy really should be an option perioperatively for all patients now, regardless of PD-L1 status. We just have to emphasize multidisciplinary evaluations of these patients so we can consider which ones might be the best candidates for neoadjuvant therapy right now, or reserving it for the adjuvant setting. Again, more survival data may help us to prefer one option versus another over time. It's nice to have two options at this point. So again, I think what this means is multidisciplinary evaluation of early stage lung cancer patients is critical, getting biomarker results as part of that evaluation is also very critical. So, again, the good news is that prognostically this is a great step forward for these patients improving. It's gonna translate into improved cure rates, without a doubt. So more news to come on this very exciting topic.

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    Greg Laub is the Senior Director of Video and currently leads the video and podcast production teams.

Primary Source

ASCO Educational Book

Luo J, et al "Overcoming KRAS-mutant lung cancer" ASCO Educ Book 2022; 42: 700-710.