ADAURA in Clinical Practice: Treatment Duration, Adherence, and Shared Decision-Making in EGFR-Mutated NSCLC

Dr. Herbst, reflecting on nearly 30 years of EGFR inhibitor research, asks Dr. Kareff how he applies the ADAURA paradigm in practice. Dr. Kareff frames the conversation around the optimism that comes with identifying an actionable mutation: for patients with resected stage IB through IIIA EGFR-mutated NSCLC, he opens the adjuvant osimertinib discussion by communicating that the mutation qualifies them for targeted therapy shown to reduce recurrence risk and improve survival. This framing, emphasizing benefit over burden, allows a more positive initial discussion even though the practical realities of a 3-year oral regimen require ongoing negotiation.

Dr. Kareff acknowledges that his patient population in South Florida skews slightly older and more geriatric on average, which makes adjuvant chemotherapy conversations more challenging; some patients in earlier stage settings question whether the chemotherapy benefit justifies the toxicity. He nonetheless pushes strongly for adjuvant chemotherapy in stage 2 and above, given established survival data, followed by adjuvant osimertinib for those who are EGFR-mutated. For earlier stage disease (stage 1B, 1C), he uses more individualized shared decision-making.

Dr. Herbst explains the rationale behind the ADAURA trial's 3-year treatment duration: earlier first-generation EGFR inhibitors such as erlotinib and gefitinib could not be tolerated for 3 years due to wild-type EGFR toxicity, and a prior erlotinib trial at 2 years was negative. Osimertinib, a third-generation mutation-selective, CNS-penetrant agent, was felt to be feasible for 3 years, and this duration was selected in close collaboration with international cooperative groups and industry. He notes that 3 years does not necessarily represent the optimal duration and that studies exploring longer adjuvant treatment are ongoing.