The ADAURA Trial: Adjuvant Osimertinib in EGFR+ Resectable NSCLC

Transcript:

Tony S.K. Mok, MD: Why don’t we move to the exciting ADAURA study? Yi-Long, you’re the best person to tell us about it. Can you briefly summarize the design of the study, the story behind the design, and the result?

Yi-Long Wu, MD, PhD: Thank you, Tony. In 2015, we had a discussion on how to design the data control trial. At that time, we had a total opinion. One was from the west of the country, who wanted the adjuvant chemotherapy and then randomized to osimertinib vs placebo. The second opinion was from the east of the country, for Japan and China. We want to compare head-to-head osimertinib vs chemotherapy because we have the 2 clinical trials. One is adjuvant from China, and 1 is the IMPACT from Japan. After the discussion in detail, I also read after the adjuvant chemotherapy, the standard of care. This is 1 important point. We think we have the total randomized clinical design. One is the head-to-head in the east of the country, and 1 is without chemotherapy. With the combination, what’s the real role of adjuvant chemotherapy? This is 1 point.

The second point is about the stage IB data. In Japan or China, we think that in stage IB, the disease lives much longer, so we want to include the patient only for stage II or III. In the west of the country, most say, “The receptor, the data—we need to cure the patient.” Also, in some patients with cancer, we want to concur in the stage IB that they did. Finally we’re balanced at this stage. We’re designed for the stage IB, which is not over 30% of patients; 70% are in stage II.

The result is very exciting. The hazard ratio for stage II and III was 0.017. The hazard ratio for stage IB to III data was 0.102. This means they reduced relapsed patients by about 87%. The result is not related to adjuvant chemotherapy. Based on these data, why did the FDA approve the indication of osimertinib as the adjuvant treatment, regardless of the stage and the adjuvant chemotherapy. Basically, they amend the result.

Tony S.K. Mok, MD: This is probably 1 of the most important papers in the past few years in terms of EGFR management, so congratulations. But there are a few controversial points. No. 1, with the design, the patient has optional chemotherapy before getting randomized. For advanced data, they got about 70% who received the chemotherapy. In stage IB, less than 30% received chemotherapy. Then in your own study, it was chemotherapy vs gefitinib. Where should we not give chemotherapy before we give osimertinib? How do we decide whether to give chemotherapy? I won’t let you answer that first. I will let Myung-Ju answer this 1 first. How would you decide when to give chemotherapy before osimertinib?

Myung-Ju Ahn, MD: There’s a lot of controversy, even in our peer group in Korea. However, chemotherapy is the only treatment to show the survivor benefit, even though the survivor benefit is 4% to 5%. Basically, chemotherapy should be given before osimertinib. However, a lot of our colleagues have not been willing to give the chemotherapy before osimertinib because most patients do not receive chemotherapy; they want an oral agent. It’s still controversial. But there are several analyses of ADAURA. The benefit was shown the regardless of the chemotherapy. So the chemotherapy can be omitted, and we can give the TKI [tyrosine kinase inhibitor] only. That’s my specialty.

Tony S.K. Mok, MD: In stage III, are you comfortable doing that? For a stage III patient, you just omit chemotherapy? For stage I, I may say that. But stage III is unclear.

Myung-Ju Ahn, MD: Exactly. That’s right.

Tony S.K. Mok, MD: Tetsuya, what do you think? Should we give chemotherapy?

Tetsuya Mitsudomi, MD, PhD: I agree with Myung-Ju’s opinion. We should give the chemotherapy because the design of the studies like that. But the study also showed that osimertinib is beneficial even without chemotherapy. If a patient refused, isn’t fit to receive cisplatin-based therapy, or is too old, then I’m happy to keep osimertinib alone.

Tony S.K. Mok, MD: Let me try to make this controversial. The 2 curves that Yi-Long has shown nicely have separated. But the patients who did not receive chemotherapy, in the study arm and the control arm, are inferior to the arm. That’s also selection bias as well.

Tetsuya Mitsudomi, MD, PhD: I thought that was because of selection bias. If the disease is more advanced, then we tend to give more chemotherapy. I think that’s why.

Myung-Ju Ahn, MD: I agree with Dr. Mitsudomi. The patient who didn’t receive chemotherapy more or less has early stage disease, and then they’re treated with chemotherapy. So there’s a bias.

Transcript edited for clarity.