Dr. Huibiao Zhang
Fudan University-affiliated Huadong Hospital
The European Lung Cancer Congress (ELCC) is one of the most anticipated academic conferences in the field of lung cancer, jointly organized by the European Society for Medical Oncology (ESMO) and the International Association for the Study of Lung Cancer (IASLC). Since its inception in 2008, ELCC has become one of the premier conferences for professionals in this field. The 2023 European Lung Cancer Congress (ELCC) took place in Copenhagen, Denmark, from March 29 to April 1. This conference featured five abstracts on osimertinib, including three adjuvant treatment studies. This article summarizes the latest research results and invites Professor Zhang Huibiao from Fudan University-affiliated Huadong Hospital to provide expert commentary from the perspective of thoracic surgery.
Abstract Number: 97P
Title: Aumolertinib as adjuvant therapy in postoperative EGFR-mutated stage I-III non-small cell lung cancer with high-risk pathological factors
Authors: Professor Shen Weiyu (Li Hui-li Hospital, Ningbo) and Professor Shen Haibo (Huamei Hospital, Ningbo)
Summary: This retrospective study explored the efficacy and safety of osimertinib as adjuvant therapy in patients with high-risk pathological factors in non-small cell lung cancer (NSCLC). A total of 115 patients with completely resected stage I-III lung adenocarcinoma, including solid, micropapillary, or complex glandular components, were included. They were divided into three groups based on genetic testing results: Group A, EGFR-positive (Ex19del/L858R), treated with osimertinib 110 mg (n=45); Group B, EGFR-positive, observation group (n=25); Group C, EGFR-negative or unknown, observation group (n=45). The primary endpoint was disease-free survival (DFS) and safety.
At the data cutoff, the one-year DFS rates for Groups A, B, and C were 100%, 88%, and 93%, respectively. The data suggested a higher rate of postoperative recurrence in EGFR-positive patients compared to EGFR-negative or unknown patients. In terms of safety, Group A had no ≥3 grade adverse events. Common adverse events included rash (15%), itching (27%), diarrhea (11%), and oral ulcers (11%), indicating good safety of osimertinib as adjuvant therapy.
Abstract Number: 98P
Title: Adjuvant osimertinib in resected EGFR-Mutated Non-Small-Cell Lung Cancer: a multiple-center real-world experience
Author: Professor Hu Jian (First Affiliated Hospital, Zhejiang University School of Medicine)
Summary: This study is a multicenter real-world study that analyzed 215 patients with EGFR-mutated (Ex19del/L858R) stage I–III non-small cell lung adenocarcinoma who underwent curative surgery. It aimed to evaluate the long-term efficacy and safety of osimertinib as adjuvant treatment in NSCLC patients. All patients received osimertinib 110 mg/d, and the duration of treatment (6-36 months) depended on pathological stage and patient condition. The study endpoints included DFS, safety, and tolerability.
At the data cutoff, all patients were followed up for more than 6 months, with no central nervous system metastasis, and one patient developed bone metastasis. The 2-year DFS was 99%. In terms of safety, 69 patients (32.1%) experienced drug-related adverse events, including rash (18.1%), diarrhea (7.0%), liver and kidney function abnormalities (5.6%), and oral ulcers (5.1%). No ≥3 grade adverse events were observed, indicating good safety.
Abstract Number: 104TiP
Title: MRD Evaluation of Osimertinib in EGFR Mutation-positive stage IB and stage IA2-3 NSCLC After Complete Surgical Resection: A Multicenter, Open-label, Single-arm Study (ASSIST)
Author: Professor Cheng Chao (First Affiliated Hospital, Sun Yat-sen University)
Summary: The ASSIST study (ChiCTR2200063184) aims to compare the difference in DFS between MRD-positive and MRD-negative patients after adjuvant osimertinib treatment in EGFR mutation-positive (Ex19del/L858R) stage IB and IA2-3 invasive NSCLC after complete surgical resection. It explores the role of MRD in guiding individualized adjuvant osimertinib treatment for NSCLC patients. The study plans to enroll 130 patients who have undergone surgery, and they will receive osimertinib 110 mg until disease progression or a maximum of 3 years of treatment. Patients will be observed based on the results of two postoperative MRD tests. The primary endpoint is the 3-year DFS rate, with secondary endpoints including the 4-year and 5-year DFS rates, overall survival (OS), and safety. This is the first study evaluating adjuvant osimertinib in EGFR mutation-positive stage IB and IA2-3 NSCLC based on MRD test results, and the first patient was enrolled in July 2022.
Dr Huibiao Zhang’s Comments
Results from large prospective clinical studies such as ADJUVANT, EVAN, EVIDENCE, and ADAURA have confirmed the survival benefits of adjuvant EGFR-TKI treatment for EGFR-mutated non-small cell lung cancer (NSCLC) patients. However, the patterns of recurrence and metastasis differ for different TKIs in these studies. The recurrence pattern for first-generation EGFR-TKIs is primarily local recurrence, with gefitinib significantly reducing the risk of extracranial metastasis in the ADJUVANT study but not reducing the risk of CNS metastasis (HR=0.75). Similarly, in the EVIDENCE study, the rate of brain metastasis for erlotinib was 7.3% (median follow-up of 24.9 months), compared to 10.6% in the adjuvant chemotherapy group, with no significant difference. Third-generation TKIs have better blood-brain barrier penetration.
The ADAURA study found that osimertinib as adjuvant treatment could better control distant metastasis, especially CNS recurrence or metastasis. Osimertinib, with its cyclopropyl moiety, enhances brain penetration, with a brain-to-plasma concentration ratio of 7.38, much higher than gefitinib and afatinib, which have ratios of 0.21 and <0.3617, respectively. In the real-world adjuvant data on osimertinib presented at ELCC 2023, the two-year DFS rate was 99%, and there were no cases of brain metastasis. These data are more promising than those reported for other EGFR-TKIs, demonstrating that osimertinib is the preferred adjuvant treatment, and we look forward to the publication of long-term benefit.
