COMMENTARY

Should ADAURA Trial Results Change Practice in NSCLC?

Mark G. Kris, MD

Disclosures

June 30, 2020

This transcript has been edited for clarity.

Hello. This is Mark Kris from Memorial Sloan Kettering Cancer Center.

For patients with stage IB, II, and IIIA locally advanced lung cancers who have had complete resections, we have good news from the ADAURA phase 3 trial that compared osimertinib with placebo. This affects the lives of thousands of patients every year in the United States, and many more patients worldwide, with resectable tumors that harbor EGFR mutations.

In April, AstraZeneca, the trial sponsor, reported that the Independent Data Monitoring Committee recommended early unblinding because they saw unprecedented efficacy results. Even at that point, the benefit of disease-free survival was such that the trial needed to be unblinded and reported.

I was not surprised by the results that showed substantial improvement in disease-free survival, which to me is the absolute most critical thing in these types of trials. We want to give our patients a life free of cancer for as long as possible or hopefully permanently—that is, cure.

We had good data in GIST tumors demonstrating that giving the tyrosine kinase inhibitor imatinib to patients adjuvantly improved disease-free survival, and also improved overall survival, with 3 years of treatment. We have many case series (from my institution and elsewhere) and some trials showing that gefitinib and erlotinib clearly improved disease-free survival [in lung cancer]. Meta-analyses proved the same thing. It's no surprise, because osimertinib is more effective than gefitinib and erlotinib in the stage IV setting and is more tolerable. That combination of greater effectiveness and tolerability would lead to clear improvements in the adjuvant setting.

In the ADAURA trial, patients received cisplatin-based chemotherapy, which remains standard of care for stage IB, II, and IIIA lung cancers.

Patients deserve a consultation as to the role of systemic therapy, and it's recommended in the guidelines. The guidelines also recommend a consultation with a radiation oncologist for stage IIIA disease to see if there is a role for postoperative radiotherapy. Both large national data collections and individual trial data demonstrate that postoperative radiotherapy for patients who had mediastinal lymph nodes at surgery also improved outcomes, both local and systemic.

These results do two things: justify testing in every patient with resected lung cancer for EGFR-mutant disease, and if so, treatment.

To those who are still going to say that disease-free survival is not the proper endpoint, I ask you to both listen and speak with your patients about their goals of care. If a tolerable therapy could improve the time free of cancer and even improve the chance of cure, patients could be willing to undertake the added burden of a medication.

It's a standard of care in most other cancers. We don't blink at 10 years of an aromatase inhibitor in patients with ER-positive breast cancer in the adjuvant setting, so we shouldn't bristle here. Treatment with osimertinib for at least 3 years is a new standard of care for patients with EGFR-mutant lung cancers.

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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