Dr Herbst on Adjuvant Osimertinib in EGFR-mutant NSCLC

Roy S. Herbst, MD, PhD, Ensign Professor, Medicine (Medical Oncology), professor, pharmacology, deputy director, Yale Cancer Center; chief, Medical Oncology, director, Center for Thoracic Cancers, Yale Cancer Center and Smilow Cancer Hospital; assistant dean for translational research, Yale School of Medicine, discusses findings from the overall survival (OS) analysis of the phase 3 ADAURA trial (NCT02511106) of adjuvant osimertinib (Tagrisso) in patients with stage IB to IIIA resected non–small cell lung cancer (NSCLC) harboring EGFR mutations.

In ADAURA, 682 patients with completely resected stage IB, II, or IIIA NSCLC were randomly assigned 1:1 to receive either osimertinib or placebo. The primary end point of this trial was disease-free survival (DFS), and key secondary end points included disease-free survival (DFS), OS, safety, and health-related quality of life.

In the primary DFS analysis of ADAURA, published in October 2020, adjuvant osimertinib led to a statistically significant DFS improvement compared with placebo. The median DFS was not yet reached in the osimertinib arm vs 27.5 months in the placebo arm, with a hazard ratio (HR) of 0.20. The updated DFS analysis, published in January 2023, showed a median DFS of 65.8 months with osimertinib vs 28.1 months with placebo, with an HR of 0.27. These DFS data supported the 2020 FDA approval of adjuvant osimertinib in patients with EGFR-mutant NSCLC.

Despite the DFS findings and regulatory approval of osimertinib in the United States and other countries, the OS data from ADAURA were still highly anticipated, Herbst says. In the patients with stage II and IIIA NSCLC, osimertinib provided an OS benefit compared with placebo. The 5-year OS rates with osimertinib and placebo were 85% and 73%, respectively, and the HR was 0.49. Additionally, in patients with stage IB, II, or IIIA disease, the 5-year OS rate with osimertinib was 88% vs 78% with placebo, translating to an HR of 0.49. An OS benefit with osimertinib was also observed across all prespecified patient subgroups analyzed, Herbst notes.

These OS data show the benefits of using a third-generation, selective, EGFR-targeted therapy in patients with resected NSCLC, Herbst explains. Osimertinib has potent central nervous system activity, and patients could receive the agent for 3 years while enrolled in the ADAURA trial because of its tolerability and survival benefits, Herbst concludes.

Disclosures: Dr Herbst reports leadership positions with American Association for Cancer Research, IASLC, Immunocore, Junshi Pharmaceuticals, Society for Immunotherapy of Cancer, and SWOG; stock and other ownership interests with Bolt Biotherapeutics, Checkpoint Therapeutics, Immunocore, and Normunity; consulting or advisory roles with AbbVie; AstraZeneca, Bolt Biotherapeutics, Bristol-Myers Squibb, Candel Therapeutics, Checkpoint Therapeutics, Cybrexa Therapeutics, DynamiCure Biotechnology, eFFECTOR Therapeutics, EMD Serono, Genentech/Roche Gilead/Forty Seven, HiberCell, I-Mab, Immune-Onc Therapeutics, Janssen, Johnson and Johnson, Junshi Pharmaceuticals, Lilly, Loxo, Merck, Mirati Therapeutics, NextCure, Normunity, Novartis Ocean Biomedical, OncoCyte, Oncternal Therapeutics, Pfizer, Refactor Health, Regeneron, Revelar, Ribon Therapeutics, Sanofi, Seagen, and Xencor; research funding from AstraZeneca, Genentech/Roche, Lilly, and Merck; and travel, accommodations, and expenses from American Cancer Society, IASLC, and SWOG.