The impact of the ALK fusion variant on clinical outcomes in EML4-ALK patients with NSCLC: a systematic review and meta-analysis

Background: Recent studies showed that ALK-fusion variants are associated with heterogeneous clinical outcomes. However, contradictory conclusions have been drawn in other studies showing no correlation between ALK variants and prognoses. Methods: A systematic review and meta-analysis was performed to evaluate the prognostic value of EML4-ALK fusion variants for patient outcomes. Results: 28 studies were included in the analysis. According to the pooled results, patients harboring variant 1 showed equivalent progression-free survival (PFS) and overall survival (OS) with non-v1 patients (hazard ratio [HR] for PFS: 0.91 [0.68–1.21]; p = 0.499; OS: 1.12 [0.73–1.72]; p = 0.610). Similarly, patients with v3 showed the same disease progress as non-v3 patients (pooled HR for PFS = 1.07 [0.72–1.58]; p = 0.741). However, pooled results for OS suggested that patients with v3 had worse survival than non-v3 patients (HR = 3.44 [1.42–8.35]; p = 0.006). Conclusion: Results suggest that patients with..... READ ARTICLE

Future Oncology DOI:10.2217/fon-2021-0945

Authors: Wang S, Luo R, Shi Y, Han X.

Review Paper, group2Kirk SmithNovember 16, 2021ALK fusion, ALK rearrangement, ALK variant, NSCLC, prognosis

High Tumor Mutation Burden and DNA Repair Gene Mutations are Associated with Primary Resistance to Crizotinib in ALK-Rearranged Lung Cancer

About 20% of patients with ALK-rearranged non-small cell lung cancer (NSCLC) develop acquired resistance to tyrosine kinase inhibitor (TKI) during the first 6 months. This study aimed to examine the molecular mechanisms of early TKI resistance and prognosis in ALK-rearranged NSCLC.Ten patients with ALK-rearranged NSCLC were included: five who developed rapid resistance to crizotinib (progression-free survival (PFS) ≤3 months) and five who exhibited a good response to crizotinib (PFS ≥36 months). The study finds a higher mutation burden and mutations in DNA repair gene, including TP53, were potentially associated with primary resistance to crizotinib in ALK-rearranged NSCLC. An immune-checkpoint inhibition strategy could be examined, which might overcome primary resistance to crizotinib in ALK-rearranged NSCLC. READ ARTICLE

OncoTargets and Therapy DOI:10.2147/OTT.S325443

Authors: Dakai Xiao, Qiuhua Deng, Dongyun He, Ying Huang, Wenchi Liang, Fengnan Wang, Haihong Yang

Case StudyKirk SmithSeptember 15, 2021ALK, non-small cell lung cancer, TKI, resistance, prognosis

Catenin Alpha-2 Mutation Changes the Immune Microenvironment in Lung Adenocarcinoma Patients Receiving Immune Checkpoint Inhibitors

Our findings provide novel insights into the underlying pathogenesis of LUAD. CTNNA2 mutation can change the immune microenvironment, thereby improving patient prognosis. The results also suggest that CTNNA2 may become a new biomarker and therapeutic target for LUAD in the future. READ ARTICLE

Frontiers in Pharmacology DOI: 10.3389/fphar.2021.645862

Authors: Wen Y., Lin A., Zhu W., Wei T., Luo P., Guo L. and Zhang J.

ALK immunohistochemistry positive, FISH negative NSCLC is infrequent, but associated with impaired survival following treatment with crizotinib

Objective: Metastasized non-small cell lung cancer (NSCLC) with an anaplastic lymphoma kinase (ALK) rearrangement is usually sensitive to a range of ALK-tyrosine kinase inhibitors. ALK-positive NSCLC have been identified in pivotal phase III trials with fluorescence in situ hybridization (ALK FISH+). These tumors are also expressing the fusion product (ALK immunohistochemistry (IHC)+). However, discrepant cases occur, including ALK IHC + FISH-. The aim of this study was to collect ALK IHC + cases and compare within this group response to crizotinib treatment of ALK FISH + cases with ALK FISH- cases. Conclusion: ALK IHC + FISH- NSCLC is infrequent and associated with a worse outcome on personalized treatment. A suitable predictive testing strategy may be to screen first with IHC and then confirm with FISH instead of considering ALK IHC equivalent to ALK FISH according to the current guidelines. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2019.09.023

Authors: E. Thunnissen, B.I. Lissenberg-Witte, M.M. van den Heuvel, K. Monkhorst, B.G. Skov, J.B. Sørensen, A. Mellemgaard, A.M.C. Dingemans, E.J.M. Speel, A.J. de Langen, S.M.S. Hashemi, I. Bahce, M.A. van der Drift, M.G. Looijen-Salamon, J. Gosney, P.E. Postmus, S.M.S. Samii, F Duplaquet, B. Weynand, X. Durando, F. Penault-Llorca, S. Finn, A.O Grady, B. Oz, N. Akyurek, R. Buettner, J. Wolf, L. Bubendorf, S. Duin, I. Marondel, L.C. Heukamp, W. Timens, E.M.D. Schuuring, P. Pauwels, E.F. Smit