Posts tagged EGFR
Effectiveness of alectinib and osimertinib in a brain metastasized lung adenocarcinoma patient with concurrent EGFR mutations and DCTN1-ALK fusion
Effectiveness of alectinib and osimertinib in a brain metastasized lung adenocarcinoma patient with concurrent EGFR mutations and DCTN1-ALK fusion

The echinoderm microtubule associated protein-like 4 gene (EML4) encodes the predominant anaplastic lymphoma kinase (ALK) fusion partner in non-small-cell lung cancer (NSCLC); however, the dynactin subunit 1 (DCTN1)-ALK rearrangement is extremely rare. The co-occurrence of primary epidermal growth factor receptor (EGFR) T790M mutation with EGFR exon 19 deletion (del) in patients with NSCLC is uncommon. Here we report a female lung adenocarcinoma patient with brain metastases and possible coexistence of primary EGFR T790M mutation/EGFR exon 19 del/DCTN1-ALK translocation. The patient received multiline treatment including chemotherapy, antivascular, and targeted therapies. To overcome developed resistance to chemotherapy or targeted therapy to prolong overall survival, the patient's circulating tumor DNA (ctDNA) was dynamically monitored. The patient responded to successive osimertinib and alectinib treatment, and alectinib achieved a nearly complete response for lung and brain lesions ..... READ ARTICLE

Thoracic Cancer DOI:10.1111/1759-7714.14291

Authors: Shuyuan Wang, Bo Yan, Yanwei Zhang, Jianlin Xu, Rong Qiao, Yu Dong, Bo Zhang, Yiming Zhao, Lele Zhang, Jie Qian, Jun Lu, Ruiying Zhao, Baohui Han

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Case Study, group1Kirk Smithalectinib, osimertinib, brain metastasis, ALK, lung, EGFR, DCTN1-ALK
Analysis of methods in the Prospective Central Lung Cancer Biomarker Registry (LungPath) from the Spanish Society of Pathology (SEAP)
Analysis of methods in the Prospective Central Lung Cancer Biomarker Registry (LungPath) from the Spanish Society of Pathology (SEAP)

Aims The aim of this study is to extend the analysis of the Lung Cancer Biomarker Testing Registry (LungPath), by analysing the techniques used in the determination of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and programmed death ligand-1 (PD-L1) for the diagnostic of patients with advanced non-small-cell lung cancer (NSCLC). Methods Information of the technique used for the determination of EGFR, ALK, ROS1 and PD-L1 was recorded from March 2018 to January 2019 from 44 centres, but only 34 centres matched with the 38 centres previously analysed, allowing to analyse the techniques used in 8970 matched determinations of EGFR, ALK, ROS1 and PD-L1. Therefore, a by-centre analysis studied the level of implementation of the techniques in the 44 centres, while a by-determination analysis made it possible to assess the overall frequency of the techniques used on the 9134 matched samples. Results By-centre analysis showed that only 46.5%..... READ ARTICLE

Journal of Clinical Pathology DOI:10.1136/jclinpath-2021-208034

Authors: Martín-López J, Rojo F, Martínez-Pozo A,Hernández-Iglesias T, Carcedo D, Ruiz de Alda L, García JF, Salas C

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Real-World Outcomes, group1Kirk SmithNSCLC, ALK, EGFR, ROS, Biomarker Testing
Outcomes of Gamma Knife Radiosurgery for Brain Metastases From Anaplastic Lymphoma Kinase Rearrangement-Positive and EGFR Mutation-Positive Non-Small Cell Lung Cancer
Outcomes of Gamma Knife Radiosurgery for Brain Metastases From Anaplastic Lymphoma Kinase Rearrangement-Positive and EGFR Mutation-Positive Non-Small Cell Lung Cancer

The outcomes after gamma knife radiosurgery (GKRS) were retrospectively analysed in patients with brain metastases from anaplastic lymphoma kinase (ALK) rearrangement-positive and epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) to evaluate the efficacy, safety and difference for overall survival and local tumor control. ALK rearrangement-positive NSCLC patients tended to have significantly longer survival, but had higher incidence of new intracranial metastases due to long-term survival after GKRS, compared with EGFR mutation-negative and driver gene mutation-negative NSCLC patients. GKRS induced significantly satisfactory local tumor control in driver gene mutation-positive tumors but GKRS-related complication frequency was higher, especially in ALK-positive NSCLC patients. Therefore, more careful imaging follow-up is necessary after GKRS for patients with driver gene mutation-positive NSCLC. READ ARTICLE

Cureus DOI:10.7759/cureus.20398

Authors: Matsunaga S and Shuto T

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Real-World Outcomes, group1Kirk SmithGamma Knife Radiosurgery (GKRS), Brain Metastases, ALK, EGFR, NSCLC
P8-133: Clinical course of the patients who survived more than five-years in patients with EGFR mutated OR ALK rearranged advanced non-small cell lung cancer (NSCLC)
P8-133: Clinical course of the patients who survived more than five-years in patients with EGFR mutated OR ALK rearranged advanced non-small cell lung cancer (NSCLC)

Background and Aims: The discovery of driver oncogenes like EGFR mutation and ALK fusion gene, and the development of their specific inhibitors have improved prognosis of NSCLC patients. Because the patients had been followed up to about 5 years in most of the clinical trials, the long-term clinical course especially after 5 years has been undefined. The object is to know clinical course after 5 years from the first chemotherapy, and to investigate factors that lead to long-term survival.
Methods: One hundred seventy-seven patients with EGFR mutated or ALK rearranged advanced NSCLC who received the first chemotherapy between December 2008 and September 2015 were included. Kaplan Meier curves were drawn for the total cohort and for the subgroups of characteristics and metastases.
Results: Median OS in the total cohort was 40.6 months, the 1-year survival rate was 89 %, the 3-year survival rate was 54 %, and the 5-year survival rate was 28 %. “Long tail” in OS curve existed, but most of ..... READ ARTICLE

Respirology DOI:10.1111/resp.14150_645

Authors: Shoko Shimamura, Takehito Shukuya, Tetsuhiko Asao, Daisuke Hayakawa, Kana Kurokawa, Shiting Xu, Yoichiro Mitsuishi, Ken Tajima, Rina Shibayama, Naoko Shimada, Fumiyuki Takahashi, Kazuhisa Takahashi

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Conference PaperKirk SmithEGFR, ALK, 5 years+
P8-170: A patient with ALK translocation-positive lung adenocarcinoma in whom an EGFR mutation developed during the treatment with ALK inhibitors
P8-170: A patient with ALK translocation-positive lung adenocarcinoma in whom an EGFR mutation developed during the treatment with ALK inhibitors

Background: Generally, ALK gene translocation and EGFR gene mutation are mutually exclusive in non-small cell lung cancer (NSCLC). We present a patient with ALK translocation-positive lung adenocarcinoma in whom an EGFR mutation developed during the treatment with an ALK inhibitors.

Case Presentation: A 70-year-old man was diagnosed with Stage IVb (cT2N3M1c) adenocarcinoma of the lung in July 20XX-8. Initial chemotherapy with CDDP+PEM was started in August, and 6 courses were performed with best response of PR. Maintenance therapy was performed for 26 courses. In May 20XX-5, multiple bone metastases emerged and 5 courses of DTX was given as the 2nd-line chemotherapy from July 20XX-5 to May 20XX-4 with the best response of SD until bone metastases developed. A trans-bronchial re-biopsy of the primary tumor in the upper lobe of the right lung revealed the translocation of ALK gene. Crizotinib was started in June as the 3rd-line chemotherapy. In August 20XX-3, multiple brain metastases de..... READ ARTICLE

Respirology DOI:10.1111/resp.14150_682

Authors: Misaki Morishita, Yoshiki Negi, Taiichiro Otsuki, Koji Mikami, Eisuke Shibata, Daisuke Horio, Maiko Niki, Akio Tada, Mayuko Tokuda, Jotaro Kiyota, Toshiyuki Minami, Ryo Takahashi, Takashi Yokoi, Kozo Kuribayashi, Takashi Kijima

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Conference PaperKirk SmithALK and EGFR co-mutation, ALK, EGFR, Co-mutation
Efficacy of Targeted Inhibitors in Metastatic Lung Squamous Cell Carcinoma With EGFR or ALK Alterations
Efficacy of Targeted Inhibitors in Metastatic Lung Squamous Cell Carcinoma With EGFR or ALK Alterations

The efficacy of targeted therapies in oncogene-driven lung adenocarcinomas (LUADs) has been well established; however, the benefit for EGFR-mutant or ALK-rearranged lung squamous cell carcinomas (LUSCs) is less known, partially owing to the rarity of the incidence. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtocrr.2021.100237

Authors: Whitney E. Lewis, Lingzhi Hong, Frank E. Mott, George Simon, Carol C. Wu, Waree Rinsurongkawong, J. Jack Lee, Vincent K. Lam, John V. Heymach, Jianjun Zhang, Xiuning Le

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Case Study, group2Kirk SmithLung squamous cell carcinoma, Targeted therapy, Tyrosine kinase inhibitor (TKI), EGFR, ALK
1356P Cumulative incidence and baseline imaging patterns of brain metastases in advanced EGFR and ALK positive non-small cell lung cancer (NSCLC)
1356P Cumulative incidence and baseline imaging patterns of brain metastases in advanced EGFR and ALK positive non-small cell lung cancer (NSCLC)

Background: Up to 40% of NSCLC patients develop brain metastases (mets) during the course of their disease. We explored the impact of histology and EGFR and ALK mutations on cumulative incidence rates of brain mets and influence of brain imaging patterns. Conclusions: Our real-world data confirm a higher cumulative incidence of brain metastases in EGFR+/ALK+ adenocarcinoma compared to WT or SCC and more brain imaging at baseline. Future analyses will focus on treatment-based outcomes (tyrosine kinase inhibitors, different radiation modalities) in EGFR+/ALK+ patients compared to WT adenocarcinoma and SCC. READ ARTICLE

Annals of Oncology DOI:10.1016/j.annonc.2021.08.1956

Authors: M.T. Chowdhury, M. García Pardo de Santayana, S. Schmid, S. Cheng, L.J. Zhan, M.C. Brown, K. Khan, P. Walia, A. Sabouhanian, E. Strom, J. Herman, N. Leighl, P. Bradbury, F.A. Shepherd, A. Sacher, W. Xu, G. Liu, D. Shultz

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Conference PaperKirk SmithCumulative incidence, baseline imaging patterns, brain metastases, EGFR, ALK, non-small cell lung cancer (NSCLC)
Brain Metastases in EGFR- and ALK-Positive NSCLC: Outcomes of Central Nervous System-Penetrant Tyrosine Kinase Inhibitors Alone Versus in Combination With Radiation
Brain Metastases in EGFR- and ALK-Positive NSCLC: Outcomes of Central Nervous System-Penetrant Tyrosine Kinase Inhibitors Alone Versus in Combination With Radiation

Management of central nervous system (CNS) metastases in patients with driver-mutated NSCLC has traditionally incorporated both tyrosine kinase inhibitors (TKIs) and intracranial radiation. Whether next generation, CNS-penetrant TKIs can be used alone without upfront radiation, however, remains unknown. This multi-institutional retrospective analysis aimed to compare outcomes in patients with EGFR- or ALK-positive NSCLC who received CNS-penetrant TKI therapy alone versus in combination with radiation for new or progressing intracranial metastases. A total of 147 patients were included (EGFR n = 94, ALK n = 52, both n = 1). In patients receiving radiation, larger metastases, neurologic symptoms, and receipt of steroids were more common. There were no significant differences between TKI and CNS radiation therapy plus TKI groups for any of the study outcomes, including time to progression (8.5 versus 6.9 mo, p = 0.13 [EFGR] and 11.4 versus 13.4 mo, p = 0.98 [ALK]), time to intracranial pr..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2021.08.009

Authors: Nicholas J.Thomas, Nathaniel J. Myall, Fangdi Sun, Tejas Patil, Rao Mushtaq, Chandler Yu, Sumi Sinha, Erqi L. Pollom, Seema Nagpal. Ross Camidge, Chad G. Rusthoven, Steve E. Braunstein, Heather A. Wakelee and Caroline E. McCoach

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Real-World Outcomes, group3Kirk SmithNon–small cell lung cancer (NSCLC), Central nervous system (CNS), ALK, EGFR, CNS radiation
SHP2 inhibition enhances the effects of tyrosine kinase inhibitors in preclinical models of treatment-naïve ALK-, ROS1-, or EGFR-altered non-small-cell lung cancer
SHP2 inhibition enhances the effects of tyrosine kinase inhibitors in preclinical models of treatment-naïve ALK-, ROS1-, or EGFR-altered non-small-cell lung cancer

After molecular-targeted therapy, some cancer cells may remain that are resistant to therapies targeting oncogene alterations, such as those in the genes encoding the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) as well as c-ros oncogene 1 (ROS1). The mechanisms underlying this type of resistance are unknown. Here we report the potential role of Src homology 2 domain-containing phosphatase 2 (SHP2) in the residual cells of ALK/ROS1/EGFR-altered non-small-cell lung cancer (NSCLC). Molecular-targeted therapies failed to inhibit the ERK signaling pathway in the residual cells whereas the SHP2 inhibitor SHP099 abolished their remaining ERK activity. SHP099 administered in combination with molecular-targeted therapy resulted in marked growth inhibition of cancer cells both in vitro and in vivo. Thus, treatment combining an SHP2 inhibitor and a tyrosine kinase inhibitor may be a promising therapeutic strategy for oncogene-driven NSCLC. READ ARTICLE

Molecular Cancer Therapeutics DOI: 10.1158/1535-7163.MCT-20-0965

Authors: Hirohisa Kano, Eiki Ichihara, Hiromi Watanabe, Kazuya Nishii, Chihiro Ando, Takamasa Nakasuka, Kiichiro Ninomiya, Yuka Kato, Toshio Kubo, Kammei Rai, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda and Katsuyuki Kiura

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Pre-Clinical, group5Kirk SmithALK, ROS1, EGFR, SHP2, NSCLC, ERK
Out-of-Pocket Costs for Tyrosine Kinase Inhibitors and Patient Outcomes in EGFR- and ALK-Positive Advanced Non–Small-Cell Lung Cancer
Out-of-Pocket Costs for Tyrosine Kinase Inhibitors and Patient Outcomes in EGFR- and ALK-Positive Advanced Non–Small-Cell Lung Cancer

Among patients with advanced EGFR- and ALK-positive NSCLC, higher TKI Out-Of-Pocket costs are associated with decreased TKI adherence, a higher likelihood of TKI discontinuation, and inferior survival. READ ARTICLE

Journal of Clinical Oncology: Oncology Practice DOI: 10.1200/OP.20.00692 JCO

Authors: Bernardo H.L. Goulart, Joseph M. Unger, Shasank Chennupati, Catherine R. Fedorenko, Scott D. Ramsey

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Real-World OutcomesKirk SmithCost, TKI, Patient Outcomes, EGFR, ALK, Advanced NSCLC
Treatment of Brain Metastases of Non-Small Cell Lung Carcinoma
Treatment of Brain Metastases of Non-Small Cell Lung Carcinoma

Lung cancer is one of the most common malignant neoplasms. As a result of the disease’s progression, patients may develop metastases to the central nervous system. The prognosis in this location is unfavorable; untreated metastatic lesions may lead to death within one to two months. Existing therapies—neurosurgery and radiation therapy—do not improve the prognosis for every patient. The discovery of Epidermal Growth Factor Receptor (EGFR)—activating mutations and Anaplastic Lymphoma Kinase (ALK) rearrangements in patients with non-small cell lung adenocarcinoma has allowed for the introduction of small-molecule tyrosine kinase inhibitors to the treatment of advanced-stage patients. The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein with tyrosine kinase-dependent activity. EGFR is present in membranes of all epithelial cells. In physiological conditions, it plays an important role in the process of cell growth and proliferation. Binding the ligand to the EGFR causes ..... READ ARTICLE

International Journal of Molecular Science DOI:10.3390/ijms22020593

Authors: Agnieszka Rybarczyk-Kasiuchnicz, Rodryg Ramlau, and Katarzyna Stencel

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Review PaperKirk Smithbrain metastases, treatment, non-small cell lung carcinoma (NSCLC), EGFR, ALK, immunotherapy
Immunotherapy in EGFR-Mutant and ALK-Positive Lung Cancer: Implications for Oncogene-Driven Lung Cancer
Immunotherapy in EGFR-Mutant and ALK-Positive Lung Cancer: Implications for Oncogene-Driven Lung Cancer

Non-small cell lung cancer (NSCLC) is a heterogeneous disease, commonly defined by genetic alterations in oncogenic drivers. Targeted therapies have transformed the management of oncogene-driven lung cancers, with targeted agents now approved in the United States for 7 distinct molecular alterations. Nonetheless, acquired resistance remains an ongoing challenge, underscoring the need for alternative therapeutic approaches. Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1) axis have emerged as important therapies in the management of advanced NSCLC, but the role of these agents in patients with oncogenic driver mutations remains unclear. Here, we focus on epidermal growth factor receptor-mutant and anaplastic lymphoma kinase-rearranged NSCLC as paradigms to explore the role of immune checkpoint inhibitors in oncogene-driven NSCLC. We provide an overview of the clinical data examining programmed death ligand 1 (PD-L1) inhibitor monotherapy, PD-(L)1 inhibitors, and tyrosine kinase inhibitor combinations, as well as combinations of PD-(L)1 inhibitors and chemotherapy. READ ARTICLE

The Cancer Journal DOI: 10.1097/PPO.0000000000000491

Authors: Gavralidis A, Gainor JF.

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Review PaperKirk SmithEGFR, ALK, combinations, Targeted therapy
Immunotherapy in EGFR-Mutant and ALK-Positive Lung Cancer
Immunotherapy in EGFR-Mutant and ALK-Positive Lung Cancer

Non-small cell lung cancer (NSCLC) is a heterogeneous disease, commonly
defined by genetic alterations in oncogenic drivers. Targeted therapies
have transformed the management of oncogene-driven lung cancers, with
targeted agents now approved in the United States for 7 distinct
molecular alterations. Nonetheless, acquired resistance remains an
ongoing challenge, underscoring the need for alternative therapeutic
approaches. Immune checkpoint inhibitors targeting the programmed cell
death 1 (PD-1) axis have emerged as important therapies in the
management of advanced NSCLC, but the role of these agents in patients
with oncogenic driver mutations remains unclear. Here, we focus on
epidermal growth factor receptor-mutant and anaplastic lymphoma
kinase-rearranged NSCLC as paradigms to explore the role of immune
checkpoint inhibitors in oncogene-driven NSCLC. We provide an overview
of the clinical data examining programmed death ligand 1 (PD-L1)
inhibitor monotherapy, PD-(L)1 inhibitors, and tyrosine kinase inhibitor
combinations, as well as combinations of PD-(L)1 inhibitors and
chemotherapy. READ ARTICLE

Cancer Journal DOI:10.1097/PPO.0000000000000491

Authors: Gavralidis A, Gainor JF

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Review PaperKirk SmithALK, EGFR, immunotherapy, oncogenic-driver, PD-1
Targeted cancer therapy induces APOBEC fuelling the evolution of drug resistance
Targeted cancer therapy induces APOBEC fuelling the evolution of drug resistance

Targeted therapy directed against EGFR and ALK oncoproteins in lung cancer induced adaptations favoring apolipoprotein B mRNA-editing enzyme, catalytic polypeptide (APOBEC)-mediated genome mutagenesis. In human oncogenic EGFR-driven and ALK-driven lung cancers and preclinical models, EGFR or ALK inhibitor treatment induced the expression and DNA mutagenic activity of APOBEC3B via therapymediated activation of NF-kB signaling. Moreover, targeted therapy also mediated downregulation of certain DNA repair enzymes such as UNG2, which normally counteracts APOBEC-catalyzed DNA deamination events. In mutant EGFR-driven lung cancer mouse models, APOBEC3B was detrimental to tumour initiation and yet advantageous to tumour progression during EGFR targeted therapy, consistent with TRACERx data demonstrating subclonal enrichment of APOBEC-mediated mutagenesis. This study reveals how cancers adapt and drive genetic diversity in response to targeted therapy and identifies APOBEC deaminases as future targets for eliciting more durable clinical benefit to targeted cancer therapy. READ ARTICLE

BioRxIV DOI:10.1101/2020.12.18.423280

Authors: Manasi K. Mayekar, View ORCID ProfileDeborah R. Caswell, Natalie I. Vokes, Emily K. Law, Wei Wu, William Hill, Eva Gronroos, Andrew Rowan, Maise Al Bakir, Caroline E. McCoach, Collin M. Blakely, Nuri Alpay Temiz, Ai Nagano, D. Lucas Kerr, Julia K. Rotow, Franziska Haderk, Michelle Dietzen, Carlos Martinez Ruiz, Bruna Almeida, Lauren Cech, Beatrice Gini, Joanna Przewrocka, Chris Moore, Miguel Murillo, Bjorn Bakker, Brandon Rule, Cameron Durfee, Shigeki Nanjo, Lisa Tan, Lindsay K. Larson, Prokopios P. Argyris, William L. Brown, Johnny Yu, Carlos Gomez, Philippe Gui, Rachel I. Vogel, Elizabeth A. Yu, Nicholas J. Thomas, Subramanian Venkatesan, Sebastijan Hobor, Su Kit Chew, Nnennaya Kanu, Nicholas McGranahan, Eliezer M. Van Allen, Julian Downward, Reuben S. Harris, Trever G. Bivona, Charles Swanton

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Pre-Clinical, Pre-PrintKirk SmithALK, EGFR, NFkB, APOBEC deaminases
Functional coding/non-coding variants in EGFR, ROS1 and ALK genes and their role in liquid biopsy as a personalized therapy
Functional coding/non-coding variants in EGFR, ROS1 and ALK genes and their role in liquid biopsy as a personalized therapy

Personalized medicine holds promise to tailor the treatment options for patients’ unique genetic make-up, behavioral and environmental background. Liquid biopsy is non-invasive technique and precise diagnosis and treatment approach. Significantly, NGS technologies have revolutionized the genomic medicine by novel identifying SNPs, indel mutations in both coding and non-coding regions and also a promising technology to accelerate the early detection and finding new biomarkers for diagnosis and treatment. The number of the bioinformatics tools have been rapidly increasing with the aim of learning more about the detected mutations either they have a pathogenic role or not. EGFR, ROS1 and ALK genes are members of the RTK family. Until now, mutations within these genes have been associated with many cancers and involved in resistance formation to TKIs. This review article summarized the findings about the mostly investigated variations in EGFR, ROS1 and ALK genes and their potential role in..... READ ARTICLE

Critical Reviews in Oncology/Hematology DOI:10.1016/j.critrevonc.2020.103113

Authors: Mahmut Cerkez Ergoren, Havva Cobanogulları, Sehime Gulsun Temel, Gamze Mocan

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Review PaperKirk SmithEGFR, ROS1, ALK, Tyrosine kinase inhibitors, Liquid biopsy, Personalized therapy
Risk of thromboembolism in patients with ALK‐ and EGFR‐mutant lung cancer: A cohort study
Risk of thromboembolism in patients with ALK‐ and EGFR‐mutant lung cancer: A cohort study

Patients with ALK‐mutant advanced lung adenocarcinoma have the highest rate of TE. TE is associated with worse survival across molecular subtypes. These findings should be taken into consideration in decision‐making regarding thromboprophylaxis. READ ARTICLE

Journal of Thrombosis Haemostasis DOI: 10.1111/jth.15215

Authors: Roopkumar J., Poudel S.K., Gervaso L., Reddy C.A., Velcheti V., Pennell N.A., McCrae K.R., Khorana A.A.

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Case StudyKirk SmithALK, EGFR, molecular subtyping, NSCLC, thromboembolism
Optimal Timing And Technique Of Local Therapy For Brain Metastases From Non-Small Cell Lung Cancer With Driver Mutations
Optimal Timing And Technique Of Local Therapy For Brain Metastases From Non-Small Cell Lung Cancer With Driver Mutations

Objective(s): Brain metastases (BM) are frequent in non-small cell lung cancer patients with driver mutations (dm-NSCLC). Since the availability of brain-penetrating tyrosine kinase inhibitors (TKI), the role of local therapy (LT) for BM from dm-NSCLC is frequently discussed. This analysis examines prognostic factors, particularly the effect of LT timing and technique, in patients with BM from dm-NSCLC. Conclusion: In this analysis, early LT improved icPFS but not OS in TKI-naive patients with BM from dm-NSCLC, compared to upfront TKI treatment. No benefit was shown for WBRT over SRS regarding either icPFS or OS. In light of the toxicities of WBRT, the choice of RT technique should be considered carefully in the context of overall prognosis and quality of life. Especially patients presenting initially with multiple BM may benefit from delaying RT or from individualized approaches like the SRS of multiple or only selected BM instead of WBRT. READ ARTICLE

International Journal of Radiation Oncology DOI:10.1016/j.ijrobp.2020.07.096

Authors: R. El Shafie, T. Eichkorn, D. Weber, F. Bozorgmehr, L. König, S. Rieken, M. Thomas, J. Debus, P. Christopoulos

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Conference PaperKirk Smithradiation, targeted therapy, brain metastases, non-small cell lung cancer (NSCLC), EGFR, ALK
22 COMPARATIVE EFFICACY OF ALK-INHIBITORS IN ALK INHIBITOR-NAIVE ALK+ LUNG CANCER BRAIN METASTASES: A NETWORK META-ANALYSIS
22 COMPARATIVE EFFICACY OF ALK-INHIBITORS IN ALK INHIBITOR-NAIVE ALK+ LUNG CANCER BRAIN METASTASES: A NETWORK META-ANALYSIS

Lung cancer has been the leading cause of cancer death for both men and women worldwide. Non-small-cell lung cancer (NSCLC) displays an array of molecular abnormalities most commonly involving ALK and EGFR pathways. NSCLC with ALK rearrangements comprises around 5% of cases. Over the years, several ALK inhibitors (ALKI) have been approved with notable activity in brain metastases. However, there have been limited comparative studies exploring their relative efficacies. This analysis was conducted to compare the relative efficacy of ALKIs against ALKI-naïve ALK+ lung cancer brain metastases.This network meta-analysis is the first to compare and rank ALKIs used in treating metastatic ALK+ lung cancer. It indicates that BRG, CER, and ALC are better therapeutic options for patients with ALK-naive ALK+ lung cancer brain metastases when compared to CRZ. READ ARTICLE

Neuro-oncology Advances DOI:10.1093/noajnl/vdaa073.012

Authors: Philip Haddad, Dalia Hammoud, Kevin Gallagher

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Real-World OutcomesKirk SmithNon-small cell lung cancer, NSCLC, ALK, EGFR
EGFR mutations and ROS1 and ALK rearrangements in a large series of non-small cell lung cancer in South India
EGFR mutations and ROS1 and ALK rearrangements in a large series of non-small cell lung cancer in South India

Aim of this study was to analyse the frequency of epidermal growth factor receptor (EGFR) mutations, ALK and ROS1 rearrangements and their association with age and gender in non-small cell lung cancer reported from a tertiary care center in South India. The study found EGFR mutations are more common than ALK and ROS1 rearrangements. They are more common in females. Patients less than 36 years have reduced frequency of EGFR mutations. Exon 19 deletion and L858R are most common and are more prevalent in lung adenocarcinomas. Rare EGFR mutations are seen in patients aged more than 50 years. READ ARTICLE

Cancer Reports DOI:10.1002/cnr2.1288

Authors: Anil Tarigopula, Gayathri Ramasubban, Vani Chandrashekar, Perumal Govindasami, hitra Chandran

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Real-World OutcomesKirk SmithALK, EGFR, non-small cell lung carcinoma, ROS1