COMMENTARY

ADAURA Trial Changes Lung Cancer Treatment in Two Important Ways

Mark G. Kris, MD

Disclosures

July 13, 2020

This transcript has been edited for clarity.

I'm Mark Kris from Memorial Sloan Kettering, commenting on presentations from the 2020 virtual ASCO meeting.

It was very weird not being there and not seeing people from around the world with energy in the fight against lung cancers. I missed that.

I'm very happy to report that we do have at least one important, practice-changing abstract, which is phase 3 of the ADAURA trial, reported by Roy Herbst, which says that 3 years of osimertinib following complete surgical resection and guideline-recommended adjuvant chemotherapy improves disease-free survival.

All patients in this trial — nearly 700 — had stage IB to IIIA disease. All had complete resections and all were at least considered for adjuvant therapy. Patients were randomized to receive either 3 years of placebo or 3 years of osimertinib at the standard dose of 80 mg daily. No new side effects were found.

The results were, some would say, amazing. Others, including myself, would say they were to be expected. The disease-free survival at 2 years was doubled from 44% with placebo to 90% with osimertinib. The hazard ratio for the primary endpoint was 0.17.

I believe that this trial met its goals. It shows important improvements in disease-free survival and does represent a new standard of care. There have been very few deaths on the trial, blessedly, with only 29 to date — 20 in the placebo arm and nine in the osimertinib arm. I think this is take-home information for people following the virtual ASCO meeting.

It changes the standard of care in two ways. First, it now makes testing for mutations a standard of care in resection specimens. At least here in the United States, that is not a standard of care today, and I think this trial will make it a standard of care.

My own personal opinion would be that the testing should be by [next-generation sequencing]. You have adequate tissue to do that. This testing can give you the data on EGFR. It could also point to other targets that may be helpful as time goes on and help guide therapy.

Second, it makes osimertinib 80 mg daily for 3 years a standard of care after surgery, after chemotherapy, and, in my mind, after postoperative radiotherapy for patients with IIIA disease.

I'm a little disheartened by the fact that less than half of patients with these disease stages were given cytotoxic chemotherapy adjuvantly.

Many people have been less enthusiastic about the results of the Herbst trial because it was disease-free survival and not overall survival. But here we have a therapy — chemotherapy — that has been proven to improve overall survival and it was given to less than half of the patients. Again, I'm sure there were characteristics that determined whether it would be a good thing (or not) for individual patients; however, we really need to make sure that adjuvant chemotherapy is on the table for discussion for every single patient. I'll add that postoperative radiotherapy should be on the table for discussion.

I'll quote the ASCO adjuvant guidelines that say that a medical oncologist should be involved in the decision-making for all of these stages. A radiation oncologist should also be involved in those patients with IIIA disease, to see about the possibility of postoperative radiotherapy. Decisions need to be individualized for IB and IIIA. However, it should be discussed in every single patient.

One other abstract I thought was of note was by Rothschild. Swiss investigators have been leaders in neoadjuvant therapies for lung cancer. Their standard has been docetaxel/cisplatin. Here, they gave docetaxel/cisplatin in the neoadjuvant setting for stage IIIA disease and then added durvalumab. They found a very good 1-year event-free survival. More data were reported in the presentation.

This is an important trial in that it affirms the results from Spain and the US that the combinations of chemotherapy and checkpoint inhibitors are very effective neoadjuvantly. Particularly for those patients who don't have a target, it represents an important advance in care. More study is going to happen with that.

There was sadness at not being in Chicago but gladness that we had such good results for patients with potentially curable lung cancers. It allows us to improve the chance for cure, which is what we want and, of course, what all of our patients and families want.

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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