Is there any prognostic significance in pleural involvement and/or effusion (Ple-I/E) in patients with ALK-positive NSCLC?
Is there any prognostic significance in pleural involvement and/or effusion (Ple-I/E) in patients with ALK-positive NSCLC?

Conclusions: Brain, liver and bone metastases are lower in ALKþpatients with Ple-I/E. Presentation with Ple-I/E in patients with ALKþ NSCLC is associated with longer overall and progression-free survival. Background: ALK mutation occurs in approximately 3-5% of patients with NSCLC. At the baseline, Ple-I/E are more frequent in ALKþ patients with NSCLC. In the study, we aimed to evaluate characteristics of ALKþpatients who have Ple-I/E. Methods: In this multicenter study, patients with ALKþ NSCLC who have Ple-I/E were retrospectively analyzed. Clinical and demographic characteristics of the disease, response rates, median PFS and OS were evaluated in 362 ALKþpatients with NSCLC. Results: Of the patients, 198 (54.7%) were male. The median age at the time of diagnosis was 54 (21-85) years. The median age was higher in male (57 vs 52 years; p¼0.011). The most common histology was adenocarcinoma (100%). At the baseline, 57 (15.7%) patients had Ple-I/E. The median age of patients with Ple-I/..... READ ARTICLE

Annals of Oncology DOI:10.1093/annonc/mdz260

Authors: Kılıçkap, Saadettin; Buğdaycı Basal, Fatma; Demirkazık, Ahmet; Gürsoy, Pınar; Demirci, Ufuk; Erman, Mustafa; Yumuk, Fulden; Çay Şenler, Filiz; Çakar, Burcu; Çiçin, İrfan; Öztürk, Akın; Coşkun, Hasan Şenol; Çubukçu, Erdem; Işıkdoğan, Abdurrahman; Ölmez, Ömer Fatih; Tatlı, Ali Murat; Karaağaç, Mehmet Onur; Sakalar, Teoman; Eralp, Yeşim; Korkmaz, Taner

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Conference PaperKirk SmithPleural involvement, effusion (Ple-I/E), ALK-positive NSCLC
P114-26 ALK Fusion Variant Detection by Targeted RNA-Seq in TKIs Treated ALK-Positive Lung Adenocarcinoma
P114-26 ALK Fusion Variant Detection by Targeted RNA-Seq in TKIs Treated ALK-Positive Lung Adenocarcinoma

We retrospectively characterized fusion variant distribution in a cohort of ALK+ lung adenocarcinomas (ADC) with paired clinical data about treatments and outcomes.Diagnostic tumor tissue from advanced ALK+ (by FISH and/or IHC) ADC diagnosed from 2010 to 2018 and treated with single or multiple ALKis were collected (expanded cohort from Gobbini et al. Lung Cancer, 2017). The OncomineTM Solid Tumor Fusion Transcript Kit on an Ion PGM™ system and the Ion Reporter™ software were used to identify targeted ALK fusion gene products (ThermoFisher).Our analysis suggests that different ALK fusion variant might affect ALKi treatment duration in ALK+ lung ADC READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1177

Authors: F. Tabbò, E. Gobbini, L. Muscarella, A. Rigutto, D. Trombetta, A. Bonfitto, D. Galetta, E. Maiello, O. Martelli, M. Tiseo, P. Bordi, V. Scotti, L. Ghilardi, V. Gregorc, C. Sergi, S. Pilotto, A. Del, Conte, F. Cappuzzo, D. Cortinovis, G. Osman, C. Bareggi, M. Di Maio, A. Rossi, G. Rossi, E. Bria, M. Volante, G. Scagliotti, P. Graziano, S. Novello, L. Righi

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Conference PaperKirk SmithALK, ALK inhibitor, Fusion variant
P114-18 ALK Inhibitor Sequencing and Outcomes Among ALK-Positive (ALK+) NSCLC Patients in the US Community Oncology Setting
P114-18 ALK Inhibitor Sequencing and Outcomes Among ALK-Positive (ALK+) NSCLC Patients in the US Community Oncology Setting

A retrospective observational cohort study of patients with ALK+ NSCLC treated with 1st generation (crizotinib) and 2nd generation (alectinib, brigatinib, ceritinib) ALK inhibitors from 1 September 2011 to 31 December 2017. Structured data were obtained via programmatic extraction from the iKnowMed EHR database of the US Oncology Network. Patient demographics and treatment sequences were characterized. Index was the start date of the first ALK. Duration of therapy (DOT) from index to end of the last ALK, and overall survival (OS) were assessed using the Kaplan-Meier method. Patients received a range of 1 to 4 ALK inhibitors. Crizotinib-led sequences were most common, likely reflecting the approval history of ALK inhibitors during the study period. Longer DOT and OS were observed in patients receiving multiple ALK inhibitors. This study provides an initial view of treatment patterns following the emergence of new ALK inhibitors and suggests feasibility of sequential ALK therapies. Follo..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1169

Authors: D. Waterhouse, J. Espirito, M. Chioda, B. Baidoo, J. Mardekian, N. Robert, E. Masters

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Conference PaperKirk SmithALK-inhibitor, treatment-sequence, NSCLC
P114-15 Lorlatinib in ALK- or ROS1-Positive Non-Small Cell Lung Cancer Patients: Experience from an Early Access Program in Turkey
P114-15 Lorlatinib in ALK- or ROS1-Positive Non-Small Cell Lung Cancer Patients: Experience from an Early Access Program in Turkey

The aim of this study is to evaluate the efficacy and safety of lorlatinib in an Expanded Access Program (EAP) in Turkey.The EAP was open-label, multicenter, and single-arm. Patients were eligible to receive lorlatinib (100 mg p.o/day) if they had advanced stage ALK- or ROS1-positive NSCLC and had progressed on crizotinib and/or second generation ALK inhibitors such as ceritinib or alectinib. The primary endpoint was PFS with lorlatinib. Secondary endpoints were objective response rate, overall survival, and safety. In this EAP, lorlatinib showed systemic activity in patients with advanced ALK+ or ROS1+ NSCLC, regardless of CNS metastases and previous TKI treatment. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1166

Authors: S. Kilickap, U. Demirci, F. Bugdayci, D. Tural, T. Korkmaz, S. Paydas, C. Yilmaz, H. Turna, A. Sezer, H. Yesil Cinkir, K. Okutur, M. Erman, Y. Eralp, D. Cabuk, A. Isikdogan, A. Demirkazik, A. Karaoglu, D. Yazilitas, F. Cay Senler, P.F. Yumuk, H. Coskun, I. Yildiz, I. Oztop, I. Beypinar, K. Aydin, M. Kaplan, N. Meydan, O.F. Olmez, O. Ozyilkan, S. Seber, C. Arslan, M.A. Sendur, I. Cicin

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Conference PaperKirk SmithALK positive, ROS1 positive, Lorlatinib, Turkey, Advanced stage lung cancer
P114-09 Unveiling Hidden MET-Mediated Primary Alectinib Resistance in ALK-Positive Non-Small Cell Lung Cancer
P114-09 Unveiling Hidden MET-Mediated Primary Alectinib Resistance in ALK-Positive Non-Small Cell Lung Cancer

More recently, alectinib has superseded crizotinib, an ALK/ROS1/MET inhibitor, as a first-line therapy due to its superiority in phase III trials. Although patients enjoy durable responses to alectinib, they eventually develop resistance. Here we describe four cases of primary resistance to alectinib in which the patients show little to no response to alectinib when administered as first or second-line therapy. In order to investigate primary resistance to alectinib, tissue was obtained during re-biopsy and subjected to routine clinical genetic analyses including gene fusion detection and genetic mutation analysis using the Archer FusionPlex and VariantPlex assays, respectively. Concurrently, at the time of biopsy, additional fresh tissue was procured for cell line derivation. The primary cell line was then used to assess ALK and other inhibitors’ potency by cell viability assays. Targeted analysis of signaling pathways was performed in the cell lines via western blot analysis and prox..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1160

Authors: A. Le, L. Tyler, K. Davies, K. Kondo, J. Pacheco, D. Merrick, D. Aisner, D.R. Camidge, R. Doebele

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Conference PaperKirk SmithALK, MET, alectinib
2-Deoxy-D-Glucose Sensitizes Non-Small Cell Lung Cancer with EML4-ALK Fusion to Crizotinib via Suppression of HK2 Through AKT/mTOR Passway
2-Deoxy-D-Glucose Sensitizes Non-Small Cell Lung Cancer with EML4-ALK Fusion to Crizotinib via Suppression of HK2 Through AKT/mTOR Passway

Background: ALK-positive NSCLC cells (ALK+ NSCLC) present high glycolysis. Targeting cancer cell metabolism with the glycolysis inhibitor, 2-deoxyglucose (2DG), is a viable strategy that sensitizes the fist-line ALK-TKI crizotinib; but the effects of combination of 2DG and Crizotinib on ALK+ NSCLC cells and the mechanism of action are unknown. Conclusion: This study demonstrated that 2DG would be a promising drugs to sensitize crizotinib via suppressing HK2 expression to inhibit the activity of AKT/mTOR signaling pathway induced by ALK phosphorylation. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1820

Authors: EML4-ALK, crizotinib, high glycolysis

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Conference PaperKirk SmithEML4-ALK, crizotinib, high glycolysis
Osimertinib Overcomes Alectinib Resistance Caused by Amphiregulin in a Leptomeningeal Carcinomatosis Model of EML4-ALK Lung Cancer
Osimertinib Overcomes Alectinib Resistance Caused by Amphiregulin in a Leptomeningeal Carcinomatosis Model of EML4-ALK Lung Cancer

Background: Central nervous system (CNS) metastasis, such as brain metastasis and leptomeningeal carcinomatosis (LMC), occurs in 20–40% of all patients with cancer. Anaplastic lymphoma kinase (ALK) is a clinically validated drug target and ALK rearrangements are found in approximately 3-5% of non-small cell lung cancer (NSCLC). ALK tyrosine kinase inhibitor (TKI) shows dramatic clinical efficacy in ALK-rearranged NSCLC patients, and the second-generation ALK-TKI alectinib is effective against CNS metastasis of ALK-rearranged NSCLC. However, the patients with ALK-rearrangement acquire resistance to alectinib over time and develop recurrent LMC metastasis. This study aimed to clarify the mechanism of resistance to alectinib in LMC and seek a novel therapeutic strategy. Conclusion: We demonstrated that EML4-ALK lung cancer cells acquired moderate resistance to alectinib in the leptomeningeal space due to amphiregulin-triggered EGFR activation. Moreover, combined use of alectinib and EGFR..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1841

Authors: S. Arai, S. Takeuchi, K. Fukuda, A. Nishiyama, A. Tanimoto, H. Taniguchi, M. Satouchi, S. Nanjo, R. Katayama, M. Nishio, M. Zheng, Y. Wu, S. Yano

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Conference PaperKirk SmithLeptomeningeal carcinomatosis, alectinib resistance, Osimertinib
P114-07 Genomic Profiling of Liquid Biopsies During 2nd/3rd Generation ALK Inhibitor Therapy to Identify Novel Mechanisms of Resistance
P114-07 Genomic Profiling of Liquid Biopsies During 2nd/3rd Generation ALK Inhibitor Therapy to Identify Novel Mechanisms of Resistance

Second- and third-generation ALK inhibitors each have diverse mechanisms of resistance. Only a fraction of resistance is due to secondary mutations of the ALK gene. Altered bypass tracts are likely the case in some other instances. Genomic alterations of other genes and pathways may be a third mechanism of resistance. Repeat liquid biopsies during the course of patients’ treatments can provide a minimally invasive method for sampling cancer-specific genomic information that leads to improved treatment selection. In the Lung Cancer Clinic of the Princess Margaret Cancer Centre, serial plasma samples were collected from six lung cancer patients with ALK rearrangement at multiple serial clinic visits pre- and post- progression on next-generation ALK inhibitors. We focused on next generation agents, as there has been previous focus on crizotinib resistance mechanisms already.The study found that broad panel-based NGS of plasma cfDNA enabled noninvasive detection of systemic (but not CNS-pr..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1158

Authors: E. Stewart, A. Wang, J. Huang, H. Bao, X. Wu, D. Patel, Z. Chen, J. Law, P. Bradbury, F. Shepherd, A. Sacher, M. Tsao, S. Bratman, N. Leighl, T. Pugh, G. Liu

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Conference PaperKirk SmithNGS, plasma, cfDNA, ALK, resistance, Genomic alterations, liquid biopsy
EML4-ALK Fusion Subtype Is Associated with Therapeutic Efficacy in Advanced Non-Small Cell Lung Cancer
EML4-ALK Fusion Subtype Is Associated with Therapeutic Efficacy in Advanced Non-Small Cell Lung Cancer

Background: The aim of this study was to investigate the molecular characteristics of each subtype of the EML4-ALK fusion gene and to evaluate the efficacy of first-line crizotinib or pemetrexed in combination with platinum in the treatment of patients with advanced NSL4-ALK fusion subtypes of advanced NSCLC. Conclusion: Among all ALK fusion subtypes, E13:A20 subtype (V1 variants) is the most common. Smoking history was a factor affecting crizotinib PFS. Compared with chemotherapy, patients with E20:A20 subtype (V2 variant) showed significant benefit with crizotinib. The median PFS of the pemetrexed combined with platinum regimen was lower than that of the E13:A20 subtype. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1830

Authors: H. Wang, H. Li, J. Ma, X. Yan, P. Li, M. Zhang, X. Zhang, G. Zhang, Z. Ma

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Conference PaperKirk SmithEML4-ALK fusion gene, Non-Small Cell Lung Cancer, Variant
Rapid Postoperative Relapse in ALK-Positive Locally Advanced NSCLC Patient with Complete Pathological Response to Neoadjuvant Crizotinib
Rapid Postoperative Relapse in ALK-Positive Locally Advanced NSCLC Patient with Complete Pathological Response to Neoadjuvant Crizotinib

In the April 2019 issue of the Journal of Thoracic Oncology, we reported cases of ALK-positive locally advanced NSCLC from two institutions in which neoadjuvant crizotinib showed quite acceptable efficacy and tolerability.1
Herein, we further describe the pathological evaluation and dynamic detection of circulating tumor DNA (ctDNA) in one patient receiving neoadjuvant crizotinib. Figure 1 summarizes the details of the entire therapeutic process. The patient is a 34-year-old male patient in whom lung adenocarcinoma and metastatic mediastinal lymph nodes were diagnosed and who received neoadjuvant crizotinib for 2 months. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.05.036

Authors: Chao Zhang, Yi-Long Wu, Wen-Zhao Zhong

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EditorialKirk SmithPostoperative Relapse, ALK-Positive, Locally Advanced NSCLC, Pathological Response, Neoadjuvant Crizotinib
Two Cases of Krukenberg Tumors from ALK-Rearranged Lung Adenocarcinoma: An Uncommon Site of Metastasis
Two Cases of Krukenberg Tumors from ALK-Rearranged Lung Adenocarcinoma: An Uncommon Site of Metastasis

Approximately 5% of all NSCLCs harbor ALK receptor tyrosine kinase gene (ALK) rearrangements.1 ALK-rearranged NSCLC is more commonly associated with younger individuals and those without a smoking history. The most common ALK rearrangement is a fusion between the ALK gene and gene echinoderm microtubule associated protein like 4 gene (EML4).1 Several drugs targeting ALK-rearranged NSCLC are currently available. Unfortunately, almost all ALK-positive NSCLCs will eventually progress during treatment with ALK inhibitors. This is mainly due to ALK point mutations, most commonly a L1196M mutation and the G1269A mutation, although several others have been identified.2 NSCLC tends to spread to the bones, brain, liver, lungs, and adrenal glands. ALK-positive NSCLCs have an increased tendency to metastasize to the pericardium, pleura, and liver compared with other NSCLCs.3 Rarely, tumors can metastasize to the ovaries; such tumors are known as Krukenberg tumors. Typically, Krukenberg tumors ori..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.05.028

Authors: John (Jack) Ogden, Hao Xie, Randolph S. Marks, Konstantinos Leventakos

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EditorialKirk SmithKrukenberg Tumors, ALK-Rearranged, Lung Adenocarcinoma, Metastasis
Exosomal Analysis of ALK Rearrangements by Spin Column with Porous Glass Filter
Exosomal Analysis of ALK Rearrangements by Spin Column with Porous Glass Filter

Background: ALK rearrangements account for about 3-5% of non-small cell lung cancer (NSCLC). ALK-tyrosin kinase inhibitors (TKI) demonstrated robust efficacy compared with cytotoxic chemotherapy in patients with ALK alterations detected in the tumor tissues. Identifying ALK rearrangement was performed using tissue samples, which are not always available. The spin column with porous glass filter has been developed by Nagoya university and AGC Inc, resulting in highly efficient and easy to use exosome isolation. The exosomes contain various molecules of their cell of origin, including proteins and RNA. The purpose of this study was to explore the spin column to capture exosome and detect ALK alterations in exosomal RNA from blood. Conclusion: Exosome remains relatively stable in the blood, making it an attractive target for liquid biopsy. Our preliminary results showed potential capability in the detection of ALK alteration in exosomes from blood. These findings require confirmation in ..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1434

Authors: T. Hatta, T. Hase, N. Ozawa, N. Yogo, H. Yukawa, H. Tanaka, D. Onoshima, M. Sato, M. Hori, Y. Baba, Y. Hasegawa

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Conference PaperKirk SmithExosome, ALK, Non-Small Cell Lung Cancer, technique
EP103-32 Prevalence of EGFR and ALK Mutations in Non Small Cell Lung Cancer in Viet Nam National Cancer Hospital
EP103-32 Prevalence of EGFR and ALK Mutations in Non Small Cell Lung Cancer in Viet Nam National Cancer Hospital

The prospective study of formalin fixed paraffin embedded (FFPE) tissues from patients diagnosed with NSCLC was performed to assess the prevalence of EGFR and ALK mutations in NSCLC in Viet Nam National Cancer Hospital. Patients with NSCLC in Viet Nam National Cancer Hospital were prospectively enrolled. FFPE tissue samples were tested for EGFR mutation by PCR and for EML4-ALK translocation by fluorescence in situ hybridization (FISH). In this sudy investigating the prevalence of EGFR and ALK mutations in non small cell lung cancer in Vietnam National Cancer Hospital, 26.2% had EGFR mutation and 10.7% had ALK translocation mutations, as compared to 35% and 6.1%, respectively, in Asian READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.2113

Authors: V. Dang

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Conference PaperKirk SmithThe prospective study of formalin fixed paraffin embedded (FFPE) tissues from patients diagnosed with NSCLC was performed to assess the prevalence of EGFR and ALK mutations in NSCLC in Viet Nam National Cancer Hospital. Patients with NSCLC in Viet Nam National Cancer Hospital were prospectively enrolled. FFPE tissue samples were tested for EGFR mutation by PCR and for EML4-ALK translocation by fluorescence in situ hybridization (FISH). In this sudy investigating the prevalence of EGFR and ALK mutations in non small cell lung cancer in Vietnam National Cancer Hospital, 26.2% had EGFR mutation and 10.7% had ALK translocation mutations, as compared to 35% and 6.1%, respectively, in Asian READ ARTICLEJournal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.2113Authors: V. Dang
EP101-62 The Safety Profile and Preliminary Efficacy of Ceritinib 450mg with Food in Chinese ALK/ROS-1 Positive NSCLC Patients
EP101-62 The Safety Profile and Preliminary Efficacy of Ceritinib 450mg with Food in Chinese ALK/ROS-1 Positive NSCLC Patients

Ceritinib have shown potent efficacy in both ALK and ROS-1 rearranged NSCLC. However, high rate of treatment interruption was suffered due to gastrointestinal or liver toxicity using Ceritinib 750mg fasting in previous study. Recently, ASCEND-8 study reported an improved tolerance and a trend to better efficacy with 450mg with food, but little data is available in Chinese patients. This first-time real-world study aims to assess the safety profile and preliminary efficacy of Ceritinib 450mg with food in Chinese patients. From Oct 2018 to March 2019, 51 ALK or ROS1 positive NSCLC patients received ceritinib were enrolled from 8 centers in Sichuan province. Safety profile and preliminary efficacy were retrospectively analyzed. The follow-up was to 31st March 2019. The study found Ceritinib 450mg with food demonstrated a good safety profile and efficacy with lower AE incidence rate and better compliance rate compare to ASCEND-8 data for Chinese patients in real-world setting...... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.2035

Authors: Y. Tian, P. Yu, X. Yin, K. Wang, M. Huang, Y. Wang, Y. Gong, J. Li

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Conference PaperKirk SmithCeritinib, non-small-cell lung cancer, Safety
EP101-56 Co-Presentation of Adenocarcinoma and Squamous Cell Lung Carcinoma Harbouring ALK Rearrangement in Different Sites
EP101-56 Co-Presentation of Adenocarcinoma and Squamous Cell Lung Carcinoma Harbouring ALK Rearrangement in Different Sites

We describe an unique case of co-presentation of ADC and SCC in two different disease sites, both harbouring ALK rearrangement. A 57-year-old male never smoker presented with a left adrenal mass. CT Scan showed a right superior lobe mass, bilateral pulmonary nodules (Fig. 1 A), and bone metastases. The lung biopsy documented ADC with moderate differentiation and ALK rearrangement by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). The patient was treated with Crizotinib but, after 4 months, the CT showed a near complete response of the pulmonary disease (Fig. 1 B), while a progression of the left adrenal metastasis was observed. (Fig. 2 A, Fig. 2B). A left adrenal biopsy showed a SCC histology, with ALK rearrangement confirmed both by IHC and FISH. The treatment was switched to alectinib without respoinse so the patient received chemotherapy. The absence of an initial biopsy of the adrenal mass doesn't allow to distinguish between a lung ADC to SCC transdiffere..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.2028

Authors: V. Longo, A. Catino, D. Galetta, G. Del Bene, R. Lacalamita, M. Montrone, F. Pesola, D. Petriella, P. Pizzutilo, S. Tommasi

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Conference PaperKirk SmithADC, SCC, ALK rearrangement
EP101-35 Concurrent Use of Low Dose Aspirin and Vitamin D in ALK, ROS and EGFR Mutant NSCLC: A Single Institution Retrospective Analysis
EP101-35 Concurrent Use of Low Dose Aspirin and Vitamin D in ALK, ROS and EGFR Mutant NSCLC: A Single Institution Retrospective Analysis

Recent meta-analysis published by Feng et al. analyzed seventeen studies and reported statistically significant reduction in risk of lung cancer by 8% when circulating 25-VD is at 10 nmol/L, this benefit was seen in both Caucasian and Asian population. To our knowledge, there have been no studies looking at influence of concurrent vitamin D or aspirin intake on outcomes in ALK, ROS and EGFR pos NSCLC treated with tyrosine kinase inhibitors. We performed a retrospective single institution analysis to study this association.Patients (pts) with ALK, ROS EGFR pos NSCLC treated with first line TKI from January 2014 to June 2017 were included. Information on concurrent use and doses of aspirin and vitamin D supplements were studied. Patients were dichotomized based on use of these individual supportive medications. Two sample t-test was used to compare mean PFS and chi-square test to compare proportions of disease control rate (DCR) at 3 months between groups.Our study did not show any diffe..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.2008

Authors: C. Bernabe, S. Sharma, J. Sanchez, K. Sullivan, N. Seetharamu

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Conference PaperKirk SmithPFS, DCR, EGFR, ROS, ALK positive, NSCLC, vitamin D, aspirin, TKI
P214-51 Dual ALK Fusion Partners as Poor Predictive Marker in First Line Crizotinib Treated ALK Rearranged Non-Small Cell Lung Cancer
P214-51 Dual ALK Fusion Partners as Poor Predictive Marker in First Line Crizotinib Treated ALK Rearranged Non-Small Cell Lung Cancer

Background: First line crizotinib response duration time differs with different fusion patterns in ALK-rearranged advanced non-small cell lung cancer (NSCLC) patients. Some former researches have elucidate the impact of EML4-ALK variants on crizotinib efficacy, however, there was little data about the efficacy of crizotinib considering different fusion partners including one patient with two or more fusion partners or non-EML4 partners. Conclusion: Efficacy of first-line crizotinib in ALK-rearranged NSCLC patients differs based on different ALK fusion partners. Dual ALK fusion partners were poor prognostic factors in first-line crizotinib treatment NSCLC. It also correlated with more brain metastasis compared with single fusion partners. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1836

Authors: Y. Zhang, L. Zeng, N. Yang, T. Jiang, C. Zhou

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Conference PaperKirk SmithNext Generation Sequencing, ALK, Fusion partners, crizotinib
MA21.05 Phase II Trial of the Combination of Alectinib with Bevacizumab in ALK-Positive Nonsquamous Non-Small Cell Lung Cancer
MA21.05 Phase II Trial of the Combination of Alectinib with Bevacizumab in ALK-Positive Nonsquamous Non-Small Cell Lung Cancer

Alectinib is a 2nd generation highly selective anaplastic lymphoma kinase (ALK) inhibitor. Although alectinib has improved progression-free survival (PFS) in patients with ALK-positive Non-Small Cell Lung Cancer (NSCLC), there are limited treatment options after progression of alectinib. Recent evidences have described promising results of the combination of bevacizumab with EGFR-TKIs, cytotoxic chemotherapies and immune-checkpoint inhibitors. We report the results from a phase II study of the combination of alectinib with bevacizumab in ALK-positive Nonsquamous NSCLC patients who were treated with alectinib and showed disease progression (UMIN 000017828) READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.676

Authors: S. Watanabe, N. Matsumoto, J. Koshio, A. Ishida, T. Tanaka, T. Abe, D. Ishikawa, S. Shoji, K. Nozaki, K. Ichikawa, R. Kondo, A. Otsubo, A. Aoki, T. Kajiwara, K. Koyama, S. Miura, H. Yoshizawa, T. Kikuchi

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Conference PaperKirk Smithalectinib, ALK, Bevacizumab, clinical trial
LBA81_PR - Phase II/III blood first assay screening trial (BFAST) in patients (pts) with treatment-naïve NSCLC: Initial results from the ALK+ cohort
LBA81_PR - Phase II/III blood first assay screening trial (BFAST) in patients (pts) with treatment-naïve NSCLC: Initial results from the ALK+ cohort

Background: Tissue-based assessment of actionable mutations in pts with NSCLC is limited by invasive biopsies and adequacy of biopsied tumour material. Blood-based testing may overcome such limitations, allowing multiplex profiling in a single test. BFAST (NCT03178552) is an ongoing multicentre, open-label, multi-cohort study evaluating the relationship between blood-based next-generation sequencing (NGS) detection of actionable genetic alterations in cell-free DNA, and the activity of targeted therapies and immunotherapy in pts with treatment-naïve advanced NSCLC. We present first results from the ALK+ cohort. Conclusions: Blood-based detection of ALK fusions results in high ORR and clinical benefit in pts receiving alectinib. These data validate the clinical utility of blood-based NGS as an additional method to inform clinical decision-making in ALK+ NSCLC. READ ARTICLE

Annals of Oncology DOI:10.1093/annonc/mdz394.079

Authors: S. M. Gadgeel, T. S. K. Mok, S. Peters, J. A. A. Alexander, N. B. Leighl, V. Sriuranpong, M. Perol, G. De Castro Jr., E. Nadal, F. De Marinis, J.-Y. Han, M. Yan, T. Riehl, E. Schleifman, S. M. Paul, S. Mocci, D. Shames, M. S. Mathisen, R. Dziadziuszko

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Clinical TrialsKirk SmithLBA81_PR - Phase II/III, blood first assay screening trial (BFAST), NSCLC, ALK+
ALK Testing in Chinese Advanced NSCLC Patients: A National-Wide Multicenter Prospective Real-World Data Study (The RATICAL Study)
ALK Testing in Chinese Advanced NSCLC Patients: A National-Wide Multicenter Prospective Real-World Data Study (The RATICAL Study)

Background: ALK-tyrosine kinase inhibitors increase ORR and PFS times in ALK-fusion positive NSCLC patients. It is therefore crucial to assess the efficacy of different methods for detecting ALK rearrangement. At present, there are most testing methods approved by cFDA to detect ALK rearrangement in China. However, many issues regarding to the procedure and quality control (QC) data of ALK testing in the routine clinical practice is still to be studied. This study is to evaluate the ALK testing platforms, testing procedures, result interpretation quality control and clinicopathological characteristics of ALK positive patients in the real world for Chinese lung cancer patients, and achieve expert consensus on the clinical practice of ALK testing. Conclusion: NSCLC patients harboring ALK gene translocation have unique clinicopathological characteristics. Some problems will still be encountered in the real world clinical practice of ALK testing, which need to be guided by establishment of expert consensus. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1034

Authors: J. Ying, L. Li, W. Li, Y. Li, Q. Xia, X. Teng, Y. Liu, G. Chen, X. Qiu, W. Wu, Ji, Z. Wang, X. Yan, Y. Han, A. The Ratical Study Group

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Conference PaperKirk SmithLung cancer, Real world data, ALK testing