Medicine Matters oncology

Hi. I'm Lecia Sequist from Massachusetts General Hospital Cancer Center in Boston Mas. And I was very thrilled to see the ADAURA results this weekend at the ASCO plenary session. This data, which I view to be very robust and very informative has been a long time in the making. We've been using EGFR inhibitors for patients with more advanced disease for 15 years. But we haven't yet had great randomized data to tell us whether this is helpful in the adjuvant setting.

Some prior studies, I would say most notably RADIANT, were not designed to really answer the question. They looked at a larger subpopulation of lung cancer patients compared to just EGFR. And then we also saw results from the CTONG study, the long-term survival results of the CTONG adjuvant study at ASCO this year.

And that also, I think, is not optimally designed in that it wasn't built on the foundation of what the standard of care already is for patients with resected non-small cell lung cancer, in other words, adjuvant chemotherapy for everybody, radiation if there's an incidental 3a, which is quite common in lung cancer. And so I think it's really hard to know how to exactly interpret all the other data that's out there.

But this randomized study was designed in the right way taking, EGFR mutated patients after they had received standard treatment and randomizing them to EGFR inhibitor or placebo. It also used osimertnib, which is the current standard of care for patients with more advanced disease. And I must say that I was really impressed by the results. So far, we have seen only the disease-free survival or the recurrence, you can think of it, and not the overall survival, which has been the historical, gold standard for adjuvant treatment.

But the overall survival is still quite immature. I think it's going to be multiple years before that data matures . And the disease-free survival hazard ratio of 0.17 is extremely impressive in my opinion. It's practice changing now, even though it is disease-free survival and not overall survival. I think I would, in my practice, I will probably talk to patients about this treatment, especially if they have higher stage disease, like stage 3a disease, where we saw among that subgroup the hazard ratio was 0.12-- incredibly robust indication that osimertnib can be helpful.

I think a couple of criticisms about this study are that, even though it was designed in what I think is the right way to incorporate the standard care adjuvant chemotherapy and then look at this question of EGFR TKI or not, unfortunately, a good portion of the patients did not receive the adjuvant chemotherapy for whatever reason. And we don't know so much about the reason. One of the main reasons may be stage of disease. So we need to see those further details, which hopefully will be included in the eventual manuscript, so we can understand why patients-- close to half of patients actually-- did not receive chemotherapy.

However, we saw in Dr. Herbst's presentation that we saw the data for both the patients who received adjuvant chemo and those that didn't. So that was reassuring because we thought even patients who didn't not receive adjuvant chemotherapy as they probably should have had a good benefit from osimertinib.

So in summary, I think that the ADAURA results are practice changing. I will certainly discuss this option with my patients. I think we are still waiting for regulatory approval. So when that comes through, if it comes through, then I will discuss this option with patients. And I think that the counterargument is that we don't have overall survival.

And I think that needs to be explained to patients that don't know if it will help them live longer. As with any adjuvant therapy, we don't know if they even need it. They may already be cured by the therapies that they've had up to that point. But the chance to have an 83% reduction in rate of recurrence, I think, is quite meaningful.