Precision Medicine: Key Updates for Treatment of NSCLC - Episode 1

ADAURA Trial; Early Stage Non–Small Cell Lung Cancer

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Benjamin Levy, MD: Hello, and welcome to this OncLive® Peer Exchange®, “Precision Medicine: Key Updates for Treatment of Non–Small Cell Lung Cancer.”

I’m Dr. Benjamin Levy. I’m an associate professor at Johns Hopkins, and I’m the clinical director for the Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital in Washington, DC. I am thrilled to be joined by a fabulous panel.

Joining me in this discussion are my colleagues: Dr Lyudmila Bazhenova from the University of California San Diego; Dr Josh Bauml from the University of Pennsylvania in Philadelphia; and Dr Becca Heist from Massachusetts General Hospital Cancer Center in Boston, Massachusetts.

Today we are going to discuss a number of important topics pertaining to the use of targeted agents in oncogene-driven lung cancers. We’ll discuss the latest data from the ASCO [American Society of Clinical Oncology] 2020 Annual Meeting and the impact of recent FDA approvals on treatment selections. It’s never been a more exciting time to be in the field of lung cancer, given all the genotype-directed therapies we have. The ability to parse out tumors into molecular subsets and wed them to targeted therapies has been exciting for physicians, but more important, the benefits gained for patients is quite incredible.

Let’s get started on our first topic. I don’t think you can have a Zoom meeting, web blast, advisory board, or virtual panel discussion without talking about ADAURA. The majority of our topics will be on advanced-stage lung cancer and the genetic alterations in advanced stages. Clearly, we’ve had some very interesting, compelling, and thought-provoking data come out at ASCO 2020 with the utility or the potential use of adjuvant osimertinib in resected EGFR lung cancer. Josh, would you walk us through the design, results, and your thoughts? Maybe after that, we can get some of the panelists’ input on this.

Joshua Bauml, MD: Sure. Thanks so much, Ben. The ADAURA study looked at patients with resectable EGFR-mutated non–small cell lung cancer who had completed adjuvant chemotherapy. The chemotherapy was at the discretion of the treating provider. This was a worldwide study, and the use of adjuvant chemotherapy certainly varies in different countries. After whatever treatment they received, patients with stage IB, II, or IIIA disease were randomized to either osimertinib once daily for 3 years, or a placebo once daily.

The primary end point of this study was disease-free survival, and that was only in patients with stage II and IIIA disease, even though stage IB was included. Already, that’s an interesting end point, right? After surgery, we want to cure patients. We want to improve overall survival. But AstraZeneca had spoken with whomever when they were designing the study, and it was agreed that disease-free survival would be a reasonable end point.

At 1 of their study-monitoring visits, they were looking at their data and they said, “These results are pretty remarkable. We have to stop the study.” That’s something that does happen when a study is being reviewed. In an unplanned analysis, they presented the findings. What they found was pretty remarkable. In patients with stage II or IIIA disease, the hazard ratio for giving osimertinib was 0.17. Put another way, there was an 83% reduction in the risk of the cancer coming back or the patient dying with the use of osimertinib. That’s remarkable. I don’t think I have seen any study with a hazard ratio that low.

Of course, the maturity here is low. Maturity is 33% for disease-free survival; overall survival data are too immature to make any conclusions. The question will be, how do we interpret these data? From my perspective, the lack of an overall survival benefit is notable. We’re going to need to follow these patients to see if we can see a survival benefit, though the likelihood of detecting that may be limited by the fact that the trial was unblinded early. But I can’t imagine this not getting an approval, given the marked improvement that was seen for our patients.

If this gains approval, I would talk about it with my patients. I find these data very compelling for patients who have stage II or IIIA disease to improve outcomes after surgery. We know that after surgery for lung cancer, outcomes are poor. This is the best improvement in outcomes that I have seen with any intervention.

The 1 concern I have is the fact that only about half the patients in the trial received chemotherapy, and that, to me, is a big issue. We know chemotherapy improves survival. I worry that someone might have been told, “Look, I have this cool trial for EGFR mutation, and I can give you chemotherapy or not give you chemotherapy.” Then, someone goes on the trial, gets randomized to placebo and they could have a bad outcome. That’s concerning to me, but I don’t know that it actually happened. Functionally, when I have these data in front of me, I feel as if they’re far too compelling to ignore.

Transcript Edited for Clarity