Mark Socinski, MD: Let’s transition to the surgical setting, and we have to recognize our guest of honor this evening, Dr Herbst, in his plenary session presentation. Roy, I want you to walk us through quickly, the ADAURA trial, and then we’ll talk a little bit about what these data mean in the surgical patients and if it should change practice and all those considerations. First, tell us the bottom line.
Roy S. Herbst, MD, PhD: Thanks, Mark. The ADAURA trial presented at ASCO [the American Society of Clinical Oncology annual meeting] was a unique and exciting study. As we know in early stage disease—I, II and IIIa—that’s resectable, we use platinum therapy where appropriate, and the recurrence rates remain high. Stage I is as high as 50%, stage II could be as high as 60% or more, and stage III is 70% or more with adjuvant therapy alone. I think what we’re seeing is now EGFR-mutated lung cancer, for many years we’ve been using these agents in the metastatic setting. Starting with gefitinib or erlotinib. We moved to afatinib, then we developed osimertinib, which is of course, an EGFR tyrosine kinase-specific drug, works against T790M. And from the FLAURA trial it was quite clear that there was improved survival with this drug over erlotinib and gefitinib.
The other thing about osimertinib is that it has very good brain penetration. The idea was now to bring this drug earlier, and to use the best targeted therapy with the best surgical and chemotherapy in early stage lung cancer. That was the ADAURA trial.
I never anticipated presenting at ASCO this year. The analysis was not planned for 2 years from now based on the number of events that were occurring. What happened was this trial, which basically was a quite simple design, patients with stage I to IIIa disease, complete resection by surgery, adjuvant therapy when appropriate. This is a physician and patient decision. They are then randomized to either receive 80 mg of osimertinib once a day orally or a placebo, and people often asked why placebo? Placebo because there is no standard of care or was no standard of care. Then the patients are followed with a planned dosing for 3 years, and the primary end point was disease-free survival.
The safety committee was reviewing the trial in April at the yearly meeting, and they noticed some trends in survival, so they asked for survival data. Remember, this trial was planned for a hazard ratio of 0.7, 30% benefit. They unblinded the trial, and the hazard ratio in the stage II and IIIa patients, the primary end point was 0.17, so 83% improvement in disease-free survival. When you add the stage I patients in, the hazard ratio was 0.21, 79% improvement. If you looked at a number of factors, race, type of mutation, this trial only took EGFR exon 19 deletions or L858R mutations, no difference in outcome. If you look at who received chemotherapy and who didn’t, no difference in outcome. In this trial, across the board was positive by all variables, and the toxicity that was seen for the osimertinib was quite mild, just a couple of percent grade 3/4, the grade 1/2s, as has been seen. Notably no problems with ILD, interstitial lung disease, which again, is a concern about using these agents in the early stage.
The trial hit all its end points. Survival is still immature. It showed a very early survival curve at ASCO, but only at 5%, so that needs to continue.
It’s a new paradigm here, Mark, using targeted therapy now in the adjuvant setting, and you can imagine we can use this for EGFR inhibition, but why not ALK or ROS1 or NTRK, or any of the other targets we have? Very exciting, and I’ll stop there and we can discuss more.
Mark Socinski, MD: Stephen, your perspective on the ADAURA trial? Is it a new standard of care? I have to admit when I saw the disease-free survival curves, it was the wow factor. You don’t see that very often.
Transcript Edited for Clarity