Genetic and treatment profiles of patients with concurrent Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) mutations

EGFR and ALK alternations often contribute to human malignancies, including lung cancer. EGFR and ALK mutations are usually sensitive to EGFR-tyrosine kinase inhibitors (TKIs) and ALK-TKIs. Although generally mutually exclusive, these mutations do co-exist in rare cases. This study investigated the frequencies, clinical characteristics, therapeutic efficacies, and genetic profiles of lung cancer patients with EGFR and ALK co-mutations. ALK and EGFR mutations coincide at a relatively low frequency in lung cancer patients. ALK mutations developed either synchronously or heterochronously with EGFR mutations. Two ALK mutations (L1152R and STRN-ALK) may co-exist with EGFR mutations at a higher frequency than others. Most EGFR/ALK co-alteration patients (other than the EGFR/ALK L1152R type) can benefit from first line EGFR-TKIs. READ ARTICLE

BMC Cancer DOI:10.1186/s12885-021-08824-2

Authors: Xiaodan Yang, Jia Zhong, Zhuo Yu, Minglei Zhuo, Min Zhang, Rongrong Chen, Xuefeng Xia & Jun Zhao

Deciphering the immunosuppressive tumor microenvironment in ALK- and EGFR-positive lung adenocarcinoma

Methods: We performed comparative mRNA expression profiling of 31 ALK-positive, 40 EGFR-positive and 43 ALK/EGFR-negative lung ADC focused on immune gene expression. The presence and levels of tumor infiltration lymphocytes (TILs) as well as fourteen specific immune cell populations were estimated from the gene expression profiles. Results:While total TILs were not lower in ALK-positive and EGFR-positive tumors compared to ALK/EGFR-negative tumors, specific immunosuppressive characteristics were detected in both subgroups: In ALK-positive tumors, regulatory T cells were significantly higher compared to EGFR-positive (fold change: FC = 1.9, p = 0.0013) and ALK/EGFR-negative tumors (FC = 2.1, p = 0.00047). In EGFR-positive tumors, cytotoxic cells were significantly lower compared to ALK-positive (FC = − 1.7, p = 0.016) and to ALK/EGFR-negative tumors (FC = − 2.1, p = 2.0E-05). A total number of 289 genes, 40 part of cytokine–cytokine receptor signaling, were differentially expressed be..... READ ARTICLE

Cancer Immunology, Immunotherapy DOI:doi.org/10.1007/s00262-021-02981-w

Authors: Jan Budczies, Martina Kirchner, Klaus Kluck, Daniel Kazdal, Julia Glade, Michael Allgäuer, Mark Kriegsmann, Claus-Peter Heußel, Felix J. Herth, Hauke Winter, Michael Meister, Thomas Muley, Torsten Goldmann, Stefan Fröhling, Martin Wermke, Cornelius F. Waller, Amanda Tufman, Martin Reck, Solange Peters, Peter Schirmacher, Michael Thomas, Petros Christopoulos, & Albrecht Stenzinger

Successful management of a lung cancer patient harbouring both EGFR mutation and EML4-ALK fusion gene with disseminated intravascular coagulation

Lung cancer patients harbouring driver oncogene alterations are markedly responsive to molecular target agents, such as epidermal growth factor receptor (EGFR), tyrosine kinase inhibitor (TKI), and echinoderm microtubule-associated protein like 4 - anaplastic lymphoma kinase (EML4-ALK)-TKI. We encountered an exceptionally rare case, harbouring both EGFR mutation and EML4-ALK fusion gene, and suffering from severe disseminated intravascular coagulation. In this case report, we present two notable points. First, our patient was successfully treated with a third-generation EGFR-TKI, osimertinib. Second, osimertinib could manage severe conditions, such as disseminated intravascular coagulation. Third-generation EGFR-TKIs may be a viable option for patients harbouring both EGFR mutations and EML4-ALK fusion genes, even in severe conditions. READ ARTICLE

Respiratory Medicine Case Reports DOI:10.1016/j.rmcr.2021.101393

Authors: Kohei Fujita, Megumi Naka, Takanori Ito, Osamu Kanai, Koichi Maekawa, Koichi Nakatani, Tadashi Mio

Concurrent EGFR mutation and ALK rearrangement in stage IV lung adenocarcinoma-a case report and a literature review

EGFR mutation and ALK rearrangement were considered mutually exclusive mutations in non-small cell lung cancer. Upfront comprehensive mutation screening, like next-generation sequencing, enabled the discovery of simultaneous mutations. We describe a case of a woman with stage IV lung adenocarcinoma with 2 synchronous mutations at diagnosis, the EGFR p.(Leu858Arg) mutation, and an ALK rearrangement. The patient is on gefitinib for 16 months, maintaining this strategy currently. Co-occurrence of 2 targetable mutations is a particular challenge when choosing first-line treatment. We discuss the treatment options and results in patients with both mutations, which were generally associated with a poor prognosis in multiple studies comparing with one single mutation. READ ARTICLE

Porto Biomedecial Journal DOI: 10.1097/j.pbj.0000000000000124

Authors: Élia Cipriano, Helena Magalhães, Catarina Tavares, João Pinto, Luís Cirnes, Fernanda Estevinho

Case StudyKirk SmithFebruary 11, 2021ALK rearrangement, EGFR mutation, concurrent EGFR and ALK mutations, NSCLC

Emerging EML4-ALK Variant 5 as a Concurrent Resistance Mechanism to Osimertinib in a Patient With EGFR E19del/T790M NSCLC

The management of patients with epidermal growth factor receptor (EGFR)-mutant, metastatic non–small-cell lung cancer (NSCLC) who become resistant to EGFR inhibitors remains challenging given the presence of complex and heterogeneous resistance mechanisms. READ ARTICLE

Clinical Lung Cancer DOI:10.1016/j.cllc.2020.05.009

Authors: Yan Yan, Guozhong Jiang, Weijie Ma, Tianhong Li, Liping Wang

Clinical Utility of Reflex Ordered Testing for Molecular Biomarkers in Lung Adenocarcinoma

Introduction: In order to standardize and expedite molecular biomarker testing, we implemented reflex ordered testing of targeted gene alterations in newly diagnosed lung adenocarcinomas within our hospital system... Conclusions: Reflex ordered testing of molecular biomarkers in lung adenocarcinoma led to significantly decreased TAT within our hospital system and higher detection rates of targeted gene alterations. READ ARTICLE

Clinical Lung Cancer DOI:10.1016/j.cllc.2020.05.007

Authors: Kartik Anand, Thuy L. Phung, Eric H. Bernicker, Philip T. Cagle, Randall J. Olsen, Jessica S. Thomas

Review PaperKirk SmithSeptember 1, 2020ALK fusion, EGFR mutation, NSCLC, ROS1 fusion, Turnaround time

EML4-ALK Fusion as a Resistance Mechanism to Osimertinib and Its Successful Management With Osimertinib and Alectinib: Case Report and Review of the Literature

As the use of up-front osimertinib for advanced epidermal growth factor receptor (EGFR)-mutant non–small-cell lung cancer is increasing, it is important to understand the resistance pathways to the drug and subsequent treatment. READ ARTICLE

Clinical Lung Cancer DOI:10.1016/j.cllc.2020.05.016

Authors: Ullas Batra, Mansi Sharma, B.P. Amrith, Anurag Mehta, Parveen Jain

Clinical relevance of PD-L1 expression and CD8+ T cells infiltration in patients with EGFR-mutated and ALK-rearranged lung cancer

EGFR-mutated or ALK-rearranged non-small cell lung cancer (NSCLC) often showed unfavorable clinical benefit to checkpoint inhibitors (CPIs). However, few reports exist with integrated analysis, to interpret the underlying mechanism of poor response to PD-1/PD-L1 inhibitors. We have retrospectively analyzed the tumor microenvironment (TME) based on tumor PD-L1 expression and CD8+ T cells infiltration in patients with EGFR mutations and ALK rearrangements, and the prognostic value of TME subtypes on overall survival (OS).
Patients with EGFR mutations or ALK rearrangements exhibited lower PD-L1 and CD8 co-expression level in TME, which could be responsible for poor response to CPIs. PD-L1 and CD8 co-expression in EGFR-mutated or ALK-rearranged lung cancer is a biomarker for poor prognosis with shorter OS. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2018.09.010

Authors: Si-yang Liu, Zhong-yi Dong, Si-pei Wu, Zhi Xie, Li-xu Yan, Yu-Fa Li, Hong-hong Yan, Jian Su, Jin-Ji Yang, Qing Zhou, Wen-Zhao Zhong, Hai-Yan Tu, Xue-Ning Yang, Xu-Chao Zhang, Yi-Long Wu