Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for EGFR-mutated resectable non-small-cell lung cancer: NeoADAURA

Abstract

Osimertinib is a third-generation, irreversible oral EGFR-tyrosine kinase inhibitor), that potently inhibits EGFR-tyrosine kinase inhibitor-sensitizing mutations and T790M resistance mutations together with efficacy in CNS metastases in patients with non-small-cell lung cancer (NSCLC). Here we describe the rationale and design for the Phase III NeoADAURA study (NCT04351555), which will evaluate neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone prior to surgery, in patients with resectable stage II-IIIB N2 EGFR mutation-positive NSCLC. The primary end point is centrally assessed major pathological response at the time of resection. Secondary end points include event-free survival, pathological complete response, nodal downstaging at the time of surgery, disease-free survival, overall survival and health-related quality of life. Safety and tolerability will also be assessed. Trial Registration number: NCT04351555 (ClinicalTrials.gov).

Keywords: EGFR-TKI-sensitizing mutations; EGFR-tyrosine kinase inhibitor; neoadjuvant; non-small-cell lung cancer; osimertinib; resectable.

Figure 1.. NeoADAURA study design.

*By 8th edition of the IASLC Staging Manual in Thoracic Oncology 2016 [37]. ^†Investigator's choice. ^‡Osimertinib will be offered for up to 3 years or until disease recurrence as a treatment choice. ^§An EFS event is defined as documented disease progression that precludes surgery or requires non-protocol treatment; recurrence or a new local or distant lesion (a new primary malignancy confirmed by pathology is not considered to be an EFS event); or death due to any cause. AUC5: Area under the curve 5; ECOG: Eastern Cooperative Oncology Group; DFS: Disease-free survival; EFS: Event-free survival; EGFRm: EGFR mutation-positive; Ex19del: Exon 19 deletion; IV: Intravenous; MPR: Major pathological response; NSCLC: Non-small-cell lung cancer; OS: Overall survival; pCR: Pathological complete response; PO: Orally; PS: Performance status; q3w: Three-times a week; qd: daily; R: Randomization.