08 Oct TAGRISSO® (osimertinib) in Resected EGFR-Mutated Non–Small-Cell Lung Cancer
MedicalResearch.com Interview with:
Roy S. Herbst, M.D., Ph.D.
Ensign Professor of Medicine (Medical Oncology) and
Professor of Pharmacology
Chief of Medical Oncology
Yale Cancer Center and Smilow Cancer Hospital
Associate Cancer Center Director for Translational Research
Yale Cancer Center
MedicalResearch.com: What is the background for this study? How does osimertinib differ from prior versions of EGFR-TKI Inhibitors?
o ADAURA is a randomized, double-blinded, global and placebo-controlled Phase III trial in the adjuvant treatment of 682 patients with Stage IB, II, and IIIA EGFRm NSCLC following complete tumor resection and adjuvant chemotherapy as indicated. Patients were treated with osimertinib 80 mg once-daily oral tablets or placebo for three years or until disease recurrence. The primary endpoint is disease free survival (DFS) in Stage II and IIIA patients, and a key secondary endpoint is DFS in Stage IB, II and IIIA patients. Osimertinib is not currently approved in the adjuvant setting in any country.
o Osimertinib is a third-generation, irreversible EGFR-TKI with clinical activity against central nervous system metastases. The results of the Phase III ADAURA trial of osimertinib demonstrate for the first time in a global trial that an EGFR inhibitor can change the course of early-stage EGFR-mutated lung cancer for patients.
o ADAURA results were first presented in May during the American Society of Clinical Oncology ASCO20 Virtual Scientific Program.
MedicalResearch.com: What are the main findings?
o The interim results from the Phase III ADAURA trial showed that osimertinib reduced the risk of disease recurrence or death by 83% in patients with Stage II and IIIA disease, a primary endpoint, and by 79% in the overall trial population of patients with Stage IB-IIIA disease, a key secondary endpoint.
o Most recently, ADAURA results were presented on September 19, 2020 during the Presidential Symposium of the European Society for Medical Oncology (ESMO) Virtual Congress 2020 (abstract #LBA1) and simultaneously published with the primary results in The New England Journal of Medicine.
o These results from a prespecified exploratory analysis of the positive ADAURA Phase III trial showed osimertinib demonstrated a clinically meaningful improvement in central nervous system (CNS) disease-free survival (DFS) in the adjuvant treatment of patients with early-stage (IB, II and IIIA) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after complete tumor resection.
- In this prespecified exploratory analysis, fewer patients treated with osimertinib in the adjuvant setting had recurrence events or deaths compared to placebo (11% versus 46%). Among patients whose cancer recurred, 38% of those treated with osimertinib had a metastatic recurrence compared to 61% of patients on placebo.
- Osimertinib reduced the risk of CNS recurrence or death by 82% (hazard ratio [HR] 0.18; 95% CI 0.10-0.33). Median CNS DFS was not yet reached in either arm.
MedicalResearch.com: What should readers take away from your report?
o These results expand on the proven efficacy of osimertinib in treating CNS metastases in the advanced setting as a result of its ability to penetrate the blood-brain barrier.
o Combined with the unprecedented DFS results in the ADAURA trial, these data support that osimertinib has the potential to change the course of resectable EGFR-mutated lung cancer for patients.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Currently, the Phase III ADAURA trial will continue to assess overall survival (OS), which is event driven, as a secondary endpoint.
MedicalResearch.com: Is there anything else you would like to add? Any disclosures?
Response: These data are transformative for patients with early-stage EGFRm NSCLC who face high rates of recurrence even after successful surgery and subsequent treatment with adjuvant chemotherapy. The ADAURA trial really offers patients new hope and the potential for future new options after their cancer has been resected. The fact that this agent delays metastasis, especially to the brain, I believe will be a great advantage to patients. Of course, we will await survival analysis.
o I have consulted with AstraZeneca.
1: Osimertinib in Resected EGFR-Mutated Non–Small-Cell Lung Cancer
Yi-Long Wu, M.D., Masahiro Tsuboi, M.D., Jie He, M.D., Thomas John, Ph.D., Christian Grohe, M.D., Margarita Majem, M.D., Jonathan W. Goldman, M.D., Konstantin Laktionov, Ph.D., Sang-We Kim, M.D., Ph.D., Terufumi Kato, M.D.,Huu-Vinh Vu, M.D., Ph.D., Shun Lu, M.D., et al., for the ADAURA Investigators*
September 19, 2020
2: ESMO 2020 abstract:
Annals of Oncology (2020) 31 (suppl_4): S1142-S1215. 10.1016/annonc/annonc325
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