It’s really been a wonderful ASCO meeting. I’m presenting the ADAURA study which is the first randomised trial of a targeted agent under the adjuvant therapy for non-small cell lung cancer EGFR mutation positive. Basically we presented the top line data, these results have only been available for the last month, or a month and a half, where we basically took patients with lung cancer, the number one cause of cancer death worldwide, and we took patients with EGFR mutation and who had had complete resection of stage 1, 2 or 3a disease. Now these patients, as you know, their outcomes even with adjuvant chemotherapy, which is standard of care for most of them, not all, and that could be delivered in this trial is the stage 1s about half will recur at five years, the stage 2 about two-thirds at five years and the stage 3s about three-quarters. So clearly new therapy was needed.
Of course, we know from the FLAURA trial that osimertinib, a third generation EGFR TKI, EGFR mutation specific, quite well tolerated, can be given for long periods of time. So we set out to do a randomised trial where we planned for three years of therapy, half the patients got osimertinib at 80mg, the other half got placebo in a blinded fashion. Many ask why placebo, well, because there is no standard of care here. These patients would have just been followed every three months after the adjuvant therapy and we’d hope that they did not recur. Now, half the patients in a blinded way got the osimertinib and I presented the top line results.
We had planned and statistically guided this trial to see a hazard ratio of 0.7, 30% improvement. We were left with a hazard ratio of 0.17 – 83% improvement – at two years 90% versus 45% of patients alive without disease. This is just extraordinary, so much better than expected. When we look at patients with stage 1, 2, 3 disease through the key secondary analysis we had a hazard ratio of 0.21 with a 79% improvement and with a very statistically significant p-value. These data actually held no matter whether the patients got chemotherapy or not and regardless of age, sex or the type of mutation – exon 19 deletion or L858R – and race. This was a multinational study – Asia, East and West – and we actually saw the same results in both parts of the world.
So this is quite significant because now we have a new practice changing trial that will give patients, and that’s what this is all about, patients with EGFR mutation this option to receive this as an adjuvant. We treated for three years, the results I present today are the disease free survival, we await overall survival. We’ll wait longer than we expected because the trial has been unblinded so early because of this tremendous result. But we’ll also soon be seeing some of the results that show that metastatic sites. I will tell you, having worked in this field for so long, that the reason why patients with lung cancer do succumb to the disease is because of metastasis – spread of the cancer to the brain, the liver and the bone. I’m quite confident that what we’re seeing here is that we’re seeing a prevention of that, allowing patients to live with their lung cancer for much longer periods of time with improved quality of life.
So, very nice to be on the plenary podium here, albeit virtual. But there has been so much communication via the internet I feel like we’re getting our word out to so many people and we’re having discussions of these data and hopefully that will occur in the months to come. But clearly a big positive step forward for patients with lung cancer through the field and despite all the issues with the virus in the world we’re continuing to make progress against this deadly disease which is so vitally important.
The data as we see them I think demonstrate immediate clinical significance. Of course now it has to be fully vetted through regulatory authorities and that will occur but with benefits of this magnitude it reminds me of what was seen initially with Herceptin in the adjuvant setting about fifteen years ago. So you bring your best drugs to the early stages of disease for the most activity, prevent disease, hopefully cure disease. But I think that’s what we’re looking at here but, of course, we’ll continue to follow these trials out longer. But first presentation clearly exceeded expectations and will be a wonderful addition to the armamentarium, once approved, for patients with locally advanced lung cancer.