The incidence of ALK inhibitor-related pneumonitis in advanced non-small-cell lung cancer patients: A systematic review and meta-analysis

Introduction: We evaluated the incidence of pneumonitis in clinical trials of anaplastic lymphoma kinase (ALK) inhibitors in patients with advanced non-small cell lung cancer (NSCLC) and compared the incidence among different cohorts, in order to identify possible predisposing factors for ALK inhibitor-related pneumonitis. Conclusions: The overall incidence of ALK inhibitor pneumonitis was 2.14% in patients with advanced NSCLS. The patients from Japanese cohorts had a higher incidence of ALK-inhibitor pneumonitis, which indicates the need for increased awareness and caution for pneumonitis in Japanese patients treated with ALK inhibitors. READ ARTICLE

Lung Cancer
DOI:10.1016/j.lungcan.2019.04.015

Authors: Chong Hyun Suh, Kyung Won Kim, Junhee Pyo, Hiroto Hatabu, Mizuki Nishino

Genomic aberrations of ALK in head and neck squamous cell carcinoma

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase encoded by the gene ALK, which belongs to a subfamily of the insulin receptor superfamily. ALK signaling has been shown to be involved in cell proliferation, differentiation, and development, etc. Thus far, ALK aberrations are known to be involved in the oncogenesis of non-small cell lung cancer and glioblastoma. Head and neck cancer squamous cell carcinoma (HNSCC) is an aggressive cancer with genomic heterogeneity as revealed by recent whole-exome studies. READ ARTICLE

Cancer Research DOI: 10.1158/1538-7445

Authors: Lan Wang, Yuchen Liu, Wenying Piao, Peony Hiu Yan Poon, Chun Kit Yeung, Amy Bik Wan Chan, Chin Wang Lau, Yuxiong Su, Jason Ying Kuen Chan and Vivian Wai Yan Lui

Real-World OutcomesKirk SmithApril 1, 2019ALK, head and neck cancer

Natural History and Factors Associated with Overall Survival in Stage IV ALK-Rearrange Non–Small Cell Lung Cancer

Clinical variables describing the natural history and longitudinal therapy outcomes of stage IV anaplastic lymphoma kinase gene rearrangement positive (ALK-positive) NSCLC and their relationship with long-term overall survival (OS) have not previously been described in detail.
Patients with stage IV NSCLC treated with an ALK inhibitor at the University of Colorado Cancer Center from 2009 through November 2017 were identified retrospectively. OS curves were constructed by using Kaplan-Meier methods. Multivariate Cox proportional hazard analysis was used to determine the relationship of variables with OS.
We concluded that patients with stage IV ALK-positive NSCLC can have prolonged OS. Brain metastases at diagnosis of stage IV disease does not influence OS. Having more organs involved with tumor at stage IV presentation is associated with worse outcomes. Prolonged benefit from pemetrexed is associated with better outcomes. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2018.12.014

Authors: Jose M. Pacheco, Dexiang Gao, Derek Smith, Thomas Purcell, Mark Hancock, Paul Bunn, Tyler Robin, Arthur Liu, Sana Karam, Laurie Gaspar, Brian Kavanagh, Chad Rusthoven, Dara Aisner, Robert Doebele, D. Ross Camidge

Efficacy of Alectinib in Patients with ALK-Positive NSCLC and Symptomatic or Large CNS Metastases

Central nervous system (CNS) metastases represent a significant source of morbidity and mortality for patients with ALK tyrosine kinase gene (ALK)-positive NSCLC. Alectinib has demonstrated robust CNS activity in both crizotinib-naive and crizotinib-resistant settings. However, the CNS efficacy of alectinib has not been established in patients with untreated symptomatic, large CNS metastases.
In this retrospective study, patients were eligible if they had advanced ALK-positive NSCLC with large (defined as ≥1 cm) or symptomatic CNS metastases and received alectinib. Medical records and radiographic imaging were reviewed to determine treatment outcomes. CNS efficacy was assessed per the modified Response Evaluation Criteria in Solid Tumors version 1.1.
Alectinib demonstrated meaningful CNS efficacy in patients with ALK-positive NSCLC with untreated symptomatic or large brain metastases. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2018.12.002

Authors: Jessica J Lin, Ginger Y Jiang, Nencyben Joshipura, Jennifer Ackil, Subba R Digumarthy, Sandra P Rincon, Beow Y Yeap, Justin F Gainor, Alice T Shaw

ROS1 Gene Rearrangements Are Associated With an Elevated Risk of Peridiagnosis Thromboembolic Events

This study aims to determine whether advanced ROS1 gene-rearranged NSCLC (ROS1+ NSCLC) has a higher than expected thromboembolic event (TEE) rate.
The risk of peridiagnostic TEEs is significantly elevated in patients with advanced ROS+ NSCLC compared to EGFR+ and KRAS+ cases. TEE risk may be similarly elevated in ALK+ NSCLC. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2018.12.001

Authors: Terry L Ng, Derek E Smith, Rao Mushtaq, Tejas Patil, Anastasios Dimou, Shuo Yang, Qian Liu, Xuefei Li, Caicun Zhou, Robert T Jones, Megan M Tu, Flora Yan, I Alex Bowman, Stephen V Liu, Siera Newkirk, Joshua Bauml, Robert C Doebele, Dara L Aisner, Dexiang Gao, Shengxiang Ren, D Ross Camidge

Real-World OutcomesKirk SmithApril 1, 2019ALK, Lung cancer, Oncogene driver, ROS1, Thrombosis

Interstitial Lung Disease Onset and Its Risk Factors in Japanese Patients With ALK-Positive NSCLC After Treatment With Crizotinib

The study objective was to determine the incidence and characteristics of drug-induced interstitial lung disease (ILD) associated with an orally available small-molecule tyrosine kinase inhibitor, crizotinib, in a real-world clinical setting.
We concluded that crizotinib therapy should be applied to the NSCLC patients with any of above risk factors under a cautious monitoring for ILD occurrence, and clinicians should pay attention to the risks of severe ILD. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2018.11.022

Authors: Akihiko Gemma, Masahiko Kusumoto, Yasuyuki Kurihara, Noriyuki Masuda, Shigeo Banno, Yutaka Endo, Hiroyuki Houzawa, Naomi Ueno, Emiko Ohki, Akinobu Yoshimura

Distribution of ALK Fusion Variants and Correlation with Clinical Outcomes in Chinese Patients with Non-Small Cell Lung Cancer Treated with Crizotinib

Objective: We investigated the prevalence of ALK rearrangements in a Chinese NSCLC population, and correlated clinical outcomes of crizotinib with different ALK partners/variants. Conclusions: This study illustrates the patterns of ALK fusion variants present in Chinese NSCLC patients and might help explain heterogeneous clinical outcomes to crizotinib treatment according to different ALK fusion variants. READ ARTICLE

Targeted Oncology DOI:10.1007/s11523-019-00631-x

Authors: Yudong Su, Xiang Long, Yang Song, Peng Chen, Shanqing Li, Huaxia Yang, Pancheng Wu, Yanyu Wang, Zhongxing Bing, Zhili Cao, Lei Cao, Yijun Wu, Zhe Zhang, Jing Liu, Bing Li, Jianxing Xiang, Ke Ma, Tengfei Zhang, Lu Zhang, Xinru Mao, Hao Liu, Puyuan Xing, Naixin Liang

Efficacy and Safety of Ceritinib (450 mg/d or 600 mg/d) With Food Versus 750-mg/d Fasted in Patients With ALK Receptor Tyrosine Kinase (ALK)–Positive NSCLC

Introduction: In an earlier report of the ASCEND-8 study (open-label, phase I, three-arm study, treatment-naive patients and pre-treated patients with advanced/metastatic NSCLC), it was shown that ceritinib 450 mg with food had comparable exposure and better gastrointestinal tolerability than 750-mg fasted. Conclusion: Ceritinib at a dose of 450 mg with food compared to 750-mg fasted showed consistent efficacy and less gastrointestinal toxicity. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.03.002

Authors: Byoung Chul Cho, Radka Obermannova, Alessandra Bearz, Mark McKeage, Dong-Wang Kim, Ullas Batra, Gloria Borra, Sergey Orlov, Sang-We Kim, Sarayut L. Geater, Pieter E. Postmus, Scott A. Laurie, Keunchil Park, Cheng-Ta Yang, Andrea Ardizzoni, Anna C. Bettini, Gilberto de Castro Jr., Flavia Kiertsman, Zhe Chen, Yvonne Y. Lau, Kalyanee Viraswami-Appanna, Vanessa Q. Passos, Rafal Dziadziuszko

Impact of EGFR Mutation and ALK Translocation on Recurrence Pattern After Definitive Chemoradiotherapy for Inoperable Stage III Non-squamous Non–small-cell Lung Cancer

Introduction: This study was aimed at clarifying the failure pattern after definitive chemoradiotherapy in patients with stage III non–small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations and/or anaplastic lymphoma kinase (ALK) translocation. Conclusions: Although the ALK-positive group showed no characteristic failure pattern, the EGFR-mutant group showed a lower rate of in-field failure and higher rate of out-of-field failure. READ ARTICLE

Clinical Lung Cancer DOI:10.1016/j.cllc.2019.02.021

Authors: Masaki Nakamura, Shun-ichiro Kageyama, Seiji Niho, Masayuki Okumura, Hidehiro Hojo, Atsushi Motegi, Naoki Nakamura, Sadamoto Zenda, Kiyotaka Yoh, Koichi Goto, Tetsuo Akimoto

Real-World OutcomesKirk SmithMarch 4, 2019ALK, CRT, EGFR, NSCLC

Relevance of Detection of Mechanisms of Resistance to ALK Inhibitors in ALK-Rearranged NSCLC in Routine Practice

Background: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have shown efficacy in the treatment of ALK-rearranged non–small-cell lung cancer (NSCLC), but the disease eventually progresses in all patients. In many cases, resistance to ALK TKIs arises through ALK mutations. Although clinical and biological data suggest variations in TKI efficacy according to the mechanism of resistance, ALK mutations are still rarely investigated in routine practice. Conclusion: Targeted next-generation sequencing is suitable for detecting ALK resistance mutations in ALK-rearranged NSCLC patients in routine practice. It might help select the best treatment at the time of disease progression during treatment with an ALK TKI. READ ARTICLE

Clinical Lung Cancer DOI:10.1016/j.cllc.2019.02.013

Authors: Philippe Jamme, Clotilde Descarpentries, Radj Gervais, Eric Dansin, Marie Wislez, Valérie Grégoire, Nicolas Richard, Simon Baldacci, Nathalie Rabbe, Maeva Kyheng, Zoulika Kherrouche, Fabienne Escande, Marie Christine Copin, Alexis B. Cortot

A study of ALK-positive pulmonary squamous-cell carcinoma: From diagnostic methodologies to clinical efficacy

Background: High concordance has been observed between Ventana D5F3 ALK immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH) in lung adenocarcinoma (LADC). However, whether a similar conclusion can be applied to lung squamous-cell carcinoma (LSCC) has remained unclear. We therefore evaluated the ALK (anaplastic lymphoma kinase) status and the therapeutic effect of an ALK tyrosine kinase inhibitor (TKI) in IHC- or FISH-positive LSCC. Conclusions: The positive concordance rate of ALK IHC and FISH in LSCC is far less than that reported for LADC. Therefore, ALK IHC detection in LSCC cannot be used as a diagnostic method for ALK rearrangement. READ ARTICLE

Lung Cancer
DOI:10.1016/j.lungcan.2019.02.015

Authors: Haiyue Wang, Leina Sun,Yaxiong Sang, Xin Yang, Guangming Tian, Ziping Wang, Jian Fang, Wei Sun, Lixin Zhou, Ling Jia, Ming-Sound Tsao, Huaiyin Shi, Dongmei Lin

Lung cancer family history and exposure to occupational/domestic coal combustion contribute to variations in clinicopathologic features and gene fusion patterns in non-small cell lung cancer

Background: Both genetic and environmental factors contribute to the development of cancer and its mutant spectrum. Lung cancer has familial aggregation. Lung cancer caused by non-tobacco factors has unique pathological and molecular characteristics. The interaction between genetic lung cancer susceptibility and carcinogens from coal burning remains complex and understudied. Conclusion: FLC and exposure to coal combustion have an important impact on the clinicopathological characteristics and gene fusion mode of NSCLC, particularly in cases of higher levels of carcinogens, and genetic susceptibility has a greater impact. Our findings may help evaluate the effect of FLC and coal exposure on the pathogenesis of lung cancer. READ ARTICLE

Thoracic Cancer
DOI:10.1111/1759-7714.12987

Authors: Ying Chen, Guangjian Li, Yujie Lei, Kaiyun Yang, Huatao Niu, Jie Zhao, Rui He, Huanqi Ning, Qiubo Huang, Qinghua Zhou, Yunchao Huang

Comprehensive analysis of PD-L1 expression, HER2 amplification, ALK/EML4 fusion, and mismatch repair deficiency as putative predictive and prognostic factors in ovarian carcinoma

Most ovarian carcinomas (OC) are characterized by poor prognosis, particularly the most frequent type high-grade serous carcinoma. Besides PARP inhibitors, target-based therapeutic strategies are not well established. We asked the question which other therapeutic targets could be of potential value and, therefore, analyzed a large cohort of OC for several predictive factors. Two hundred eighty-eight (288) cases of OC including the major histological types were analyzed by immunohistochemistry for PD-L1HER2, ALK, and the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6. HER2 amplification and ALK/EML4 fusion were assessed by fluorescence in situ hybridization. The most frequent finding was PD-L1 expression ≥ 1% in 19.5% of the cases, which correlated with a significantly better overall survival in multivariate analysis (p < 0.001). HER2 amplification was detected in 11 cases (4%), all high-grade serous carcinomas. Amplification of HER2 did not correlate with patients’ survival...... READ ARTICLE

Virchows Archiv DOI:10.1007/s00428-019-02528-6

Authors: Elisa Schmoeckel, Sophie Hofmann, Daniel Fromberger, Miriam Rottmann, Beate Luthardt, Alexander Burges, Udo Jeschke, Thomas Kirchner, Sigurd F. Lax, Doris Mayr

Concomitant resistance mechanisms to multiple tyrosine kinase inhibitors in ALK-positive non-small cell lung cancer

ALK tyrosine kinase inhibitors (TKIs), including crizotinib and several next generation TKIs, have demonstrated beneficial clinical outcomes in ALK-positive non-small cell lung cancer (NSCLC). However, resistance mechanisms following multiple TKI treatments in ALK-positive NSCLC are not fully elucidated.
Mutation profiles of 422 cancer-relevant genes in 52 patients with post-TKI biopsy samples were analyzed using next-generation sequencing (NGS), and compared between patients receiving crizotinib alone (n = 35) and multi-TKIs (n = 17).
Concurrent ALK activating mutations and/or upregulated bypass signaling are more enriched in patients undergoing multiple ALK TKI treatments compared to crizotinib alone. Concomitant TP53 mutation correlated to unfavorable survival when receiving a single TKI crizotinib. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2018.11.024

Authors: Yongfeng Yu, Qiuxiang Ou, Xue Wu, Hairong Bao,
Yan Ding, Yang W. Shao, Shun Lu

Efficacy and Safety of Lorlatinib in Korean Non–Small-Cell Lung Cancer Patients With ALK or ROS1 Rearrangement Whose Disease Failed to Respond to a Previous Tyrosine Kinase Inhibitor

Non–small-cell lung cancer (NSCLC) patients harboring ALK or ROS1 rearrangements invariably acquire resistance to the first- and second-generation tyrosine kinase inhibitors (TKIs), most notably ALK G1202R and ROS1 G2032R. Lorlatinib, a novel third-generation TKI, produced remarkable results from the first-in-man phase 1 trial: an overall response rate of 46% and 50% for previously treated ALK- and ROS1-positive patients, respectively. However, the efficacy of lorlatinib has not been widely validated in Asian patients.
This study is the first to report that lorlatinib is an important novel therapeutic option for Asian patients who have advanced NSCLC harboring ALK/ROS1 mutations whose disease progressed during treatment with first- and second-generation TKIs. READ ARTICLE

Clinical Lung Cancer DOI:10.1016/j.cllc.2018.12.020

Authors: Jiyun Lee, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Yoon La Choi, Myung-Ju Ahn

Real-World OutcomesKirk SmithDecember 31, 2018ALK, ROS1, Lorlatinib, Asian

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

Excellent Outcomes with Radiosurgery for Multiple Brain Metastases in ALK and EGFR Driven Non–Small Cell Lung Cancer

Radiosurgery for multiple BMs is controversial, yet patients with EGFR-mutated and ALK-rearranged NSCLC may be uniquely suited to benefit from this approach. These results support single and multiple courses of radiosurgery without WBRT for patients with oncogene-addicted NSCLC with four or more BMs. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2017.12.006

Authors: Tyler P. Robin, Ross Camidge, Kelly Stuhr, Sameer K. Nath, Robert E. Breeze, Jose M. Pacheco, Arthur K. Liu, Laurie E. Gaspar, Thomas Purcell, Robert C. Doebele, Brian D. Kavanagh and Chad G. Rusthoven

Impact of EML4-ALK Variant on Resistance Mechanisms and Clinical Outcomes in ALK-Positive Lung Cancer

Advanced anaplastic lymphoma kinase (ALK) fusion-positive non–small-cell lung cancers (NSCLCs) are effectively treated with ALK tyrosine kinase inhibitors (TKIs). However, clinical outcomes in these patients vary, and the benefit of TKIs is limited as a result of acquired resistance. Emerging data suggest that the ALK fusion variant may affect clinical outcome, but the molecular basis for this association is unknown. We identified 129 patients with ALK-positive NSCLC with known ALK variants. ALK resistance mutations and clinical outcomes on ALK TKIs were retrospectively evaluated according to ALK variant. A Foundation Medicine data set of 577 patients with ALK-positive NSCLC was also examined. Specific ALK variants may be associated with the development of ALK resistance mutations, particularly G1202R, and provide a molecular link between variant and clinical outcome. ALK variant thus represents a potentially important factor in the selection of next-generation ALK inhibitors. READ ARTICLE

Journal of Clinical Oncology DOI:10.1200/JCO.2017.76.2294

Authors: Lin JJ, Zhu VW, Yoda S, Yeap BY, Schrock AB, Dagogo-Jack I, Jessop NA, Jiang GY, Le LP, Gowen K, Stephens PJ, Ross JS, Ali SM, Miller VA, Johnson ML, Lovly CM, Hata AN, Gainor JF, Iafrate AJ, Shaw AT, Ou SI

Real-World OutcomesKirk SmithApril 20, 2018EML4-ALK, Variant, Resistance

Diagnostic accuracy of PCR for detecting ALK gene rearrangement in NSCLC patients: A systematic review and meta-analysis

NGS evaluation with the Oncomine Solid Tumour Fusion transcript kit and RT-PCR proved to have high sensitivity and specificity, advocating their use in routine practice. For maximal sensitivity and specificity, ALK status should be assessed by using two techniques and a third one in discordant cases. We therefore propose a customizable testing algorithm. These findings significantly influence existing testing paradigms and have clear clinical and economic impact. READ ARTICLE

Journal of Thoracic Oncology DOI: 10.1016/j.jtho.2017.11.117

Authors: Igor Letovanec, Stephen Finn, Panagiota Zygoura, Paul Smyth, Alex Soltermann, Lukas Bubendorf, Ernst-Jan Speel, Antonio Marchetti, Daisuke Nonaka, Kim Monkhorst, Henrik Hager, Miguel Martorell, Aleksandra Sejda, Richard Cheney, Javier Hernandez-Losa, Eric Verbeken, Walter Weder, Spasenija Savic, Alessia Di Lorito, Atilio Navarro, Enriqueta Felip, Arne Warth, Paul Baas, Peter Meldgaard, Fiona Blackhall, Anne-Marie Dingemans, Hendrik Dienemann, Rafal Dziadziuszko, Johan Vansteenkiste, Cathal O'Brien, Thomas Geiger, Jon Sherlock, Jeoffrey Schageman, Urania Dafni, Roswitha Kammler, Keith Kerr, Erik Thunnissen, Rolf Stahel, Solange Peters, Rolf A. Stahel, Rafael Rosell, Fiona Blackhall, Urania Dafni, Keith M. Kerr, Miguel Ángel Molina, Lukas Bubendorf, Walter Weder, Erik Thunnissen, Solange Peters, Stephen Finn, Anita Hiltbrunner, Roswitha Kammler, Thomas Geiger, Nesa Marti, Urania Dafni, Zoi Tsourti, Varvara Polydoropoulou, Panagiota Zygoura, Stephen Finn, Paul Smyth, Cathal O’Brien, Steven Gray, Walter Weder, Alex Soltermann, Isabelle Opitz, Alessandra Curioni, Lukas Bubendorf, Spasenija Savic, Didier Lardinois, Anne-Marie Dingemans, Ernst-Jan M. Speel, Andrea Ruland, Antonio Marchetti, Alessia Di Lorito, Graziano De Luca, Sara Malatesta, Fiona Blackhall, Daisuke Nonaka, Anne Marie Quinn, Lynsey Franklin, Wojciech Biernat, Ania Wrona, Witold Rzyman, Jacek Jassem, Peter Meldgaard, Henrik Hager, Line B. Madsen, Carlos Camps, Miguel Martorell, Eloisa Jantus-Lewintre, Ricardo Guijarro, Keith M. Kerr, Marianne Nicolson, David A.J. Stevenson, William Mathieson, Paul Baas, Jeroen de Jong, Kim Monkhorst, Erik Thunnissen, Egbert Smit, Coralien van Setten, Joop de Langen, Enriqueta Felip, Javier Hernandez-Losa, Irene Sansano, Richard Cheney, Mary Beth Pine, Mary Reid, Elizabeth Taylor, Kristiaan Nackaerts, Christophe Dooms, Els Wauters, Sara Van Der Borght, Hendrik Dienemann, Thomas Muley, Arne Warth

ALK in Lung Cancer: Past, Present, and Future

In 2007, scientists discovered that anaplastic lymphoma kinase (ALK) gene rearrangements are present in a small subset of non–small-cell lung cancers. ALK-positive cancers are highly sensitive to small-molecule ALK kinase inhibitors, such as crizotinib. Phase I and II studies of crizotinib in ALK-positive lung cancer demonstrated impressive activity and clinical benefit, leading to rapid US Food and Drug Administration approval in 2011. Although crizotinib induces remissions and extends the lives of patients, cures are not achieved as resistance to therapy develops. In this review, we will discuss the history of this field, current diagnostic and treatment practices, and future challenges and opportunities to advance outcomes for patients with ALK-positive lung cancers. READ ARTICLE

Journal of Clinical Oncology DOI: 10.1200/JCO.2012.44.5353

Authors: Alice T. Shaw, Jeffrey A. Engelman

Real-World OutcomesKirk SmithMarch 10, 2013ALK, crizotinib, variants