Management of Stage III NSCLC Rapid Update

ASCO Guidelines

Dr. Megan Daly presents the latest rapid recommendation update to the ASCO management of stage III NSCLC guideline, based on data from the phase III randomized LAURA trial, presented at the 2024 ASCO Annual Meeting, and subsequently published. She discusses the results of the trial, shares the updated recommendation from the expert panel, and the impact for both clinicians and patients. We also discuss future research in the area and exciting new developments to watch out for in the field. Read the full rapid update, “Management of Stage III Non-Small Cell Lung Cancer: ASCO Rapid Guideline Update” at www.asco.org/thoracic-cancer-guidelines.

TRANSCRIPT

This guideline, clinical tools, and resources are available at www.asco.org/thoracic-cancer-guidelines. Read the full text of the guideline and review authors’ disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-24-01324.

Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO’s podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one at asco.org/podcasts.

My name is Brittany Harvey, and today I'm interviewing Dr. Megan Daly from the University of California Davis Comprehensive Cancer Center, lead author on, “Management of Stage III Non–Small-Cell Lung Cancer: ASCO Rapid Guideline Update.”

Thank you for being here today, Dr. Daly.

Dr. Megan Daly: Thanks for having me, Brittany.

Brittany Harvey: Great. Then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Daly, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes.

So then, to start us off on the content of this update, first, this guideline was updated based off new evidence presented at the 2024 ASCO Annual Meeting. Dr. Daly, could you describe the trial that prompted this rapid update to the management of stage III non-small cell lung cancer guideline?

Dr. Megan Daly: The trial that prompted this update is the LAURA trial. The LAURA trial was a phase III randomized trial conducted in patients with unresectable stage III non-small cell lung cancer harboring EGFR mutations, either exon 19 deletions or L858R insertions. Patients in this trial were randomized 2:1 between the third generation EGFR tyrosine kinase inhibitor osimertinib or placebo, and osimertinib or placebo were continued until progression or other reasons for discontinuation. Osimertinib was found to provide a considerable benefit in progression free survival, with a hazard ratio of 0.16. The median progression free survival for patients randomized to osimertinib was 39.1 months, and for patients on the placebo arm, it was 5.6 months. We did not yet have overall survival data from the LAURA trial. The data is not mature, but the considerable progression free survival benefit noted with osimertinib has drawn a lot of interest to this trial.

Brittany Harvey: Absolutely. Thank you for describing the results of those trials and the endpoints. So then, based on this new evidence, what is the updated recommendation from the guideline expert panel?

Dr. Megan Daly: The updated recommendation from the panel is that patients with unresectable stage III non-small cell lung cancer with an EGFR exon 19 deletion or exon 21 L858R mutation may be offered consolidation osimertinib after definitive chemoradiotherapy, which can be either platinum-based chemotherapy and thoracic radiation given either concurrently or sequentially. Our evidence quality is moderate and the strength of the recommendation is strong.

Brittany Harvey: Great. And thank you for reviewing both the strength of the recommendation there as well as the evidence quality rating. So it's great to have this new option for patients. So what should clinicians know as they implement this new recommendation?

Dr. Megan Daly: I think it's important for clinicians to know when they're counseling patients about considering osimertinib to understand that first, the LAURA trial enrolled patients who had common EGFR mutations. So exon 19 deletions or L858R mutations. Patients with other uncommon EGFR mutations were not included in the trial. It's important to know that overall survival data is not yet mature. We do not know yet whether the use of consolidation osimertinib leads to a survival benefit at this time. We only know that it leads to a progression-free survival benefit as compared to placebo. I think it's also important to know that there was increased toxicity noted on the experimental arm. Grade 3 or higher adverse events was significantly higher with the use of osimertinib. So these are all important considerations when counseling patients and considering the use of osimertinib.

Brittany Harvey: Absolutely. Those are definitely key points, as you mentioned, to consider. And you've already touched on this a little bit. But how does this change impact patients living with stage III non-small cell lung cancer?

Dr. Megan Daly: We do see in the LAURA trial a rather remarkable benefit for progression-free survival. The progression-free survival, as I already mentioned, increased from 5.6 months median on the control arm to 39.1 months on the experimental arm with consolidation osimertinib. So this is an exciting new option for patients with unresectable stage III non-small cell lung cancer who have one of these mutations to extend their progression-free survival by almost three years. And we hope that this progression-free survival benefit will end up translating into a considerable overall survival benefit as well. So, certainly, the overall survival data is eagerly awaited.

Brittany Harvey: Definitely, this is a promising option for patients, and we look forward to future readouts of long-term data on this trial. So that's one of the outstanding questions here. But what other outstanding questions are there regarding the management of stage III non-small cell lung cancer?

Dr. Megan Daly: I think what many of us question when we look at this data is whether we could extrapolate to the use of other targeted agents with other less common oncogenic driver mutations. Unfortunately, the answer is we simply don't know yet. We hope to see some ongoing data in the resectable setting. Doing randomized trials with rare oncogenic drivers in unresectable stage III lung cancer is very difficult, unfortunately, and there's always a degree of extrapolation for clinicians when trying to figure out how to best manage our patients. But for me, that's one of the biggest outstanding questions I think specifically ties into interpreting the LAURA trial and other related trials in patients with oncogenic driver mutations.

I think there's still many outstanding questions about how we continue to improve outcomes for our patients with unresectable stage III non-small cell lung cancer, questions about how we optimize our radiation regimens to have the best possible local control while reducing toxicity. We still need to continue to have randomized trials looking at questions on optimizing radiation, optimizing concurrent chemotherapy, whether there are any settings where we might be able to reduce or omit chemotherapy in place of some of these newer agents. These are all outstanding questions that hopefully will be answered over the next several years. We also continue to have open questions about when patients are more appropriate for surgery and more appropriate for non-surgical options, those borderline patients with N2 nodes who may technically be surgical candidates or could potentially be downstaged with neoadjuvant therapy. So, I think there's a lot of exciting work going on in stage III right now.

Brittany Harvey: Absolutely. We'll look forward to that more data that you mentioned for more optimal individualized options for these patients with stage III non-small cell lung cancer.

And I want to thank you so much for your time to rapidly update this guideline based off new evidence presented and then published. And thank you for your time today, Dr. Daly.

Dr. Megan Daly: Thank you, Brittany. It's great to be on here.

Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline update, go to www.asco.org/thoracic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.

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