Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB–IIIA non-small-cell lung cancer
Roy S. Herbst, Thomas John, Christian Grohé, Jonathan W. Goldman, Terufumi Kato, К. К. Лактионов, Laura Bonanno, Marcello Tiseo, Margarita Majem, Manuel Dómine, Myung‐Ju Ahn, Dariusz M. Kowalski, M. Pérol, Virote Sriuranpong, Mustafa Özgüroğlu, Preetida J. Bhetariya, Aleksandra Markovets, Yuri Rukazenkov, Caitlin Muldoon, Jacqulyne Robichaux, Ryan J. Hartmaier, Masahiro Tsuboi, Yi‐Long Wu
Abstract
Osimertinib-a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor-is recommended as adjuvant therapy for resected stage IB-IIIA epidermal growth factor receptor-mutated non-small-cell lung cancer, based on significant disease-free survival (DFS) and overall survival improvement shown in the previously reported phase 3 ADAURA trial. A trend toward an increased DFS event rate after completion of 3 years adjuvant treatment in ADAURA suggests that some patients may benefit from longer adjuvant osimertinib treatment. We therefore explored whether tumor-informed, circulating tumor DNA-based, molecular residual disease (MRD) could predict recurrence in an exploratory post hoc analysis of 220 patients (n = 112 osimertinib; n = 108 placebo) from ADAURA. MRD preceded imaging DFS events in this study by a median of 4.7 (95% confidence interval, 2.2-5.6) months. DFS and MRD event-free rate at 36 months was 86% versus 36% for patients in the osimertinib versus placebo groups (hazard ratio, 0.23 (95% confidence interval, 0.15-0.36)). In the osimertinib group, DFS or MRD events were detected in 28 (25%) patients; most events occurred following osimertinib cessation (19 of 28, 68%) and within 12 months of stopping osimertinib (11 of 19, 58%). At 24 months after osimertinib, the DFS and MRD event-free rate was 66%. In this study, MRD preceded DFS events in most patients across both arms. DFS and MRD event-free status was maintained for most patients during adjuvant osimertinib treatment and posttreatment follow-up, with most MRD or DFS events occurring after osimertinib treatment discontinuation or completion. MRD detection could potentially identify patients who may benefit from longer adjuvant osimertinib, although this requires clinical confirmation. ClinicalTrials.gov identifier: NCT02511106 .