Abstract 410P
Background
Anaplastic lymphoma kinase (ALK) have been recognized as the most important predictor of response to crizotinib. However, 20-30% of patients harboring ALK fusion non-small-cell lung cancer patients show a poor response requiring investigation for underlying mechanisms.
Methods
We screened 3207 patients with NSCLC for ALK fusion. Among them, 92 patients received crizotinib treatment,and a total of 81 patients with stage IIIb-IV ALK+NSCLC were undergoing tumor biopsies or blood withdrawing by the time of primary or acquiring resistance to crizotinib, including 43 formalin-fixed paraffin-embedded (FFPE) samples, 25 serum samples and 24 serous effusions. We used targeted NGS to detect genes status of patients.
Results
Among 92 patients treated with crizotinib, 76.09% (70/92) developed acquired resistance, and 11.96% (11/92) had primary resistance. Using the specimens at the baseline, there were 2 (18.18%) patients with BCL2L11 loss (BIM deletion polymorphism), 1 (9.09%) patient with PTEN mutation, 1 (9.09%) patient with PIK3CA mutation, 1 (9.09%) patient with CCND1 mutation, 1 (9.09%) patient with SMARCA4 mutation, 1 (9.09%) patient with CMTR1-ALK, 1 (9.09%) patient with EML4-ALK fusion (non A20), and 3 (27.27%) patients with unknown status.
Conclusions
BCL2L11 loss, PI3K-AKT-mTOR signaling pathway (PTEN, PIK3CA mutations), SMARCA4 mutations or EML4-ALK fusion (non A20) might contribute to molecular mechanisms of primary resistance to crizotinib in ALK+NSCLC.Further investigations are warranted to overcome these primary resistance.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Chun-wei Xu.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
420TiP - UpSwinG: Real-world study of TKI activity in patients with EGFR mutation-positive (EGFRm+) NSCLC with uncommon mutations, and sequencing of afatinib followed by osimertinib
Presenter: Satoru Miura
Session: e-Poster Display Session
443TiP - A multicenter, open-label, randomized phase II study to compare the efficacy and safety of lenvatinib in combination with ifosfamide and etoposide versus ifosfamide and etoposide in children, adolescents, and young adults with relapsed or refractory osteosarcoma (OLIE; ITCC-082)
Presenter: Nathalie Gaspar
Session: e-Poster Display Session
7P - Machine learning intratumoral and axillary lymph node magnetic resonance imaging radiomics for predicting axillary lymph node metastasis in patients with early-stage invasive breast cancer (RBC-01 Study)
Presenter: Yujie Tan
Session: e-Poster Display Session
8P - Knowledge, practice and attitudes of physicians in low- and middle-income countries (LMIC) on fertility and pregnancy-related issues in young breast cancer patients
Presenter: Shah Zeb Khan
Session: e-Poster Display Session
9P - Survival status of elderly women with HR+ early breast cancer: An analysis of SEER database
Presenter: Wang Hao
Session: e-Poster Display Session
10P - Neoadjuvant immunotherapy plus chemotherapy in early triple-negative breast cancer: A meta-analysis of randomized controlled trials
Presenter: Jessa Gilda Pandy
Session: e-Poster Display Session
11P - Genetically predicted bipolar disorder is causally associated with increased risk of breast cancer: A Mendelian randomization analysis
Presenter: Haoxin Peng
Session: e-Poster Display Session
12P - Stromal tumour-infiltrating lymphocytes in human epidermal growth factor receptor 2-overexpressing breast cancer: Association with negative nodal metastasis
Presenter: Ren Xiaoqiu
Session: e-Poster Display Session
13P - A retrospective observational study on neoadjuvant chemotherapy in older adults based on the Joint Breast Cancer Registry Singapore
Presenter: Johan Chan
Session: e-Poster Display Session