Abstract 560P
Background
This study represents, to our knowledge, the first cohort study investigation into the efficacy and safety of a triple-targeted therapy comprising EGFR/BRAF/MEK inhibitors dabrafenib, trametinib and osimertinib for NSCLC patients with acquired BRAF V600E mutation after EGFR-TKI treatment. Patient-derived organoid (PDO) experiments were conducted to further elucidate the drug response.
Methods
A retrospective review of medical records was performed in multi-centers to analyze EGFR-mutant advanced NSCLC patients who developed acquired BRAF V600E mutation following EGFR-TKI treatment. All patients subsequently received dabrafenib, trametinib and osimertinib treatment. Clinical characteristics were documented, and progression-free survival (PFS) and adverse events (AEs) were assessed. In vivo drug response of PDOs were observed concurrently. Next-generation sequencing (NGS) was performed upon progression to triple-targeted therapy.
Results
Twelve patients with NGS-detected acquired BRAF V600E mutations were included in the study. Following triple-targeted therapy, the corresponding objective response rate (ORR) and disease control rate (DCR) was 58.3%, and 83.3%, respectively. The median PFS was 13.5 (95% CI: 9.8-17.2) months. No patients discontinued the treatment due to severe AEs. PDOs derived from one patient’s tumor sample were established, revealing that the triple-targeted therapy demonstrated a significantly lower IC50 value compared to other regimens. The tumor growth inhibitory rate was 99.36% for dabrafenib, trametinib plus osimertinib, 99.25% for osimertinib plus vemurafenib, 98.92% for osimertinib, encorafenib plus cetuximab, and 62.83% for pemetrexed plus carboplatin, respectively. NGS analysis identified major resistance mechanism following triple-targeted therapy, including EGFR-dependent pathway, EGFR and BRAF V600E-dependent pathway, and off-target mechanism.
Conclusions
EGFR/BRAF/MEK triple-targeted therapy is an effective and safety approach for treating acquired BRAF V600E mutation in EGFR-mutant NSCLC patients resistant to EGFR-TKIs.
Clinical trial identification
Editorial acknowledgement
Thanks for supports of Novartis
Legal entity responsible for the study
J. Yang.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
506P - Intrathoracic progression is still the most dominant failure pattern after first-line chemo-immunotherapy in extensive-stage small-cell lung cancer: Implications for thoracic radiotherapy
Presenter: Byoung Hyuck Kim
Session: Poster Display
Resources:
Abstract
519P - Final results and subgroup analysis of ORIENTAL: A phase IIIB study of durvalumab plus platinum-etoposide in first-line treatment of Chinese patients with extensive-stage small-cell lung cancer (ES-SCLC)
Presenter: Ying Cheng
Session: Poster Display
Resources:
Abstract
520P - Role of atezolizumab in controlling CNS progression in ES-SCLC
Presenter: Yoon Namgung
Session: Poster Display
Resources:
Abstract
521P - Camrelizumab combined with chemotherapy and apatinib as first-line therapy for extensive-stage small cell lung cancer: A phase II, single-arm, exploratory research
Presenter: Yanbin Zhao
Session: Poster Display
Resources:
Abstract
522P - Durvalumab plus etoposide and carboplatin for extensive-stage small cell lung cancer with mild idiopathic interstitial pneumonia
Presenter: Ichiro Nakachi
Session: Poster Display
Resources:
Abstract
523P - Camrelizumab plus apatinib as maintenance treatment in patients with extensive-stage small cell lung cancer who were responding or stable after standard first-line chemotherapy (CAMERA): Results from a single-arm, phase II trial
Presenter: Qi Wang
Session: Poster Display
Resources:
Abstract
524P - Treatment pattern and overall survival by lines of therapy among patients with advanced small cell lung cancer in Taiwan
Presenter: Kelly Huang
Session: Poster Display
Resources:
Abstract
525P - Development of diagnostic prediction score for malignant pleural effusion in lung cancer: MPE-Lung score
Presenter: Chaichana Chantharakhit
Session: Poster Display
Resources:
Abstract
526P - Burden and trends of tracheal, bronchus, and lung (TBL) cancer in Southeast Asia, East Asia, and Oceania from 1990-2019, and its projection of deaths to 2040: A benchmarking analysis
Presenter: Monika Chhayani
Session: Poster Display
Resources:
Abstract
527P - Efficacy of intraventricular chemotherapy with pemetrexed for leptomeningeal metastasis from lung adenocarcinoma: A retrospective study
Presenter: Fang Cun
Session: Poster Display
Resources:
Abstract