Clinical Activity of Crizotinib in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) Harboring Ros1 Gene Rearrangement

Ou, S.; Camidge, D. Ross; Engelman, J. A.; Clark, John R.; Tye, L.; Wilner, K.; Stephenson, Patricia; Varella‐Garcia, Marileila; Iafrate, A. John; Shaw, Alice T.; Hainaut, Pierre; Ma, Xiaoyan; Lacas, Benjamin; Tsao, Ming‐Sound; Douillard, Jean-Yves; Rousseau, Vanessa; Dunant, Ariane; Seymour, Lesley; Filipits, Martin; Graziano, Stephen L.; He, Jianxing; Yang, Huanming; Deng, Qiuhua; He, Ping; Jiang, Juhong; Zhao, Meiling; Gu, Xia; Zheng, Li-Mou; Pang, Haifeng; Zhou, Jeff X.; Reinmuth, Niels; Scherer, S.J.; Penzel, Roland; Schnabel, P.; Meister, Michael; Kiemle-Kallee, Joachim; Reuß, Alexander; Fischer, J. R.; Wolf, Michael; Thomas, Michael; Laffert, Maximilian von; Berg, Erika Gebel; Lenze, Dido; Lohneis, Philipp; Hummel, Michael; Dietel, Manfred; Han, Xiaohong; Ma, Li; Liu, Y.; Zhang, N.N.; Li, D.; Shi, Y.; Furugaki, Koh; Iwai, Toshiki; Moriya, Yoichiro; Fujimoto-Ouchi, Kaori; Mok, T.; Park, K.; Geater, Sarayut Lucien; Agarwal, Sandeep K.; Han, Mingquan; Credi, Marc; McKee, Kathryn S.; Kuriyama, Naohisa; Slichenmyer, William J.; Tan, Eng‐Huat; Greillier, L.; Martel-Lafay, Isabelle; Arpin, D.; Pourel, N.; Chabaud, Sylvie; Lamy, R.; Madroszyk, Anne; Fournel, P.; Strøm, Hans Henrik; Sundstrøm, Stein; Helbekkmo, Nina; Bremnes, Roy M.; Aasebø, Ulf; Elmpt, Wouter van; Öllers, Michel; Dingemans, Anne‐Marie C.; Lambin, Philippe; Ruysscher, Dirk De; Topkan, Erkan; Parlak, C.; Topuk, Savaş; Özyılkan, Özgür; Uyterlinde, Wilma; Vincent, A.; Belderbos, J.; Korse, T.; Baas, Paul; Heuvel, Marieke van den; Satouchi, Miyako; Chiba, Yasutaka; Yamamoto, Noboru; Nishimura, Yasumasa; Tsujino, Kazuyuki; Fujisaka, Yasuhito; Kudoh, Shinzoh; Hida, Toyoaki; Atagi, Shinji; Nakagawa, Kazuhiko; Ianotti, N.; Thongprasert, Sumitra; Spira, Alexander I.; Smith, Debbie; Lee, V.; Lim, W.T.; Gopalakrishna, Prashanth; Reynolds, Christopher M.; Nogami, Naoyuki; Sekiguchi, Risa; Enatsu, Sotaro; Tamura, Tomohide; Çetin, İlknur Alsan; Çetinkaya, Ziya; Yumuk, Perran Fulden; Dane, Faysal; Karaüç, G.; Sunnetci, N.; Turhal, Nazım Serdar; Atasoy, Beste Melek; Schirmacher, Peter; Kreipe, Hans; Büttner, Reinhard; Petersen, Iver; Jochum, Wolfram; Wang, S.; Li, J.; Hu, Xingsheng; Wang, X.; Gui, Lin; Zhao, Lingdi; Sun, Yongkun; Butts, Charles; Murray, R. Nevin; Smith, Colum J; Ellis, Peter; Jasas, Kevin; Maksymiuk, Andrew W.; Goss, Glen; Falk, M.; Loos, Anja H.; Soulieres, D.; Chabowski, Mariusz; Ramlau, Rodryg; Dyszkiewicz, Wojciech; Chouaki, N.; Soldatenkova, Victoria; Varea, R.; Barriga, Susana; Visseren‐Grul, Carla; Orłowski, T; Rubio, Joaquín Casal; Taboada, B.; Lázaro, Martín; Vázquez, S.; Firvida, X.L.; Villar, M. Vieito; Hernández, Elena; Castro, J.E.; Baron, F.; Pena, Carolina; Wanders, Rinus; Baardwijk, Angela van; Reymen, Bart; Bootsma, Gerben; Sonke, Jan‐Jakob; Pless, Miklos; Betticher, Daniel; Droege, C.; Salzberg, Marc; Moos, Roger von; Niho, Seiji; Nokihara, Hiroshi; Nihei, Keiji; Akimoto, Tetsuo; Sumi, Minako; Ito, Yoshiaki; Sekine, Ikuo; Kubota, Keiichi; Ohe, Yuichiro; Sharifi, Hoda; Vandendries, R; Das, Marco; Nalbantov, Georgi; Oellers, M.; Ramaekers, BL; Joore, MA; Lueza, Béranger; Bonastre, Julia; Mauguen, Audrey; Pignon, Jean‐Pierre; Péchoux, C. Le; Grutters, Janneke P.C.; Hotta, Katsuyuki; Kiura, Katsuyuki; Yoshizawa, H; Borget, Isabelle; Pérol, Maurice; Pérol, David; Lavolé, A.; Gervais, Radj; Zalcman, Gérard; Vergnenègre, A.; Chouaïd, C.; Qi, Wei-Xiang; Yao, Yaxian; Shen, Zhirong; He, Aina; Lin, Feng; Halim, I. Abdel; Elashry, Mohamed I.; El-Sadda, W.; Temraz, S.; Grigorescu, Alexandru; Turtoi, I.; Boeru, S.E.; Копп, М. В.; Koroleva, Irina; Kozlov, Sergey V.; Шаплыгин, Л. В.; Е, Попова М; Kutyreva, J.G.

doi:10.1093/annonc/mds408

Cited by 10 publications

(3 citation statements)

References 16 publications

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“…Based on this preclinical data, a phase I trial of crizotinib (ClinicalTrials.gov identifier NCT00585195) was amended to include a ROS1-positive cohort. Preliminary results from this trial were presented at the 2012 American Society of Clinical Oncology annual meeting and updated at the 2012 European Society for Medical Oncology congress [46,47]. Twenty ROS1positive NSCLC patients were evaluable at the time of reporting.…”

Section: Targeting Ros1mentioning

confidence: 99%

Novel Targets in Non-Small Cell Lung Cancer: ROS1 and RET Fusions

2013

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The discovery of chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene in non-small cell lung cancer (NSCLC) has stimulated renewed interest in oncogenic fusions as potential therapeutic targets. Recently, genetic alterations in ROS1 and RET were identified in patients with NSCLC. Like ALK, genetic alterations in ROS1 and RET involve chromosomal rearrangements that result in the formation of chimeric fusion kinases capable of oncogenic transformation. Notably, ROS1 and RET rearrangements are rarely found with other genetic alterations, such as EGFR, KRAS, or ALK. This finding suggests that both ROS1 and RET are independent oncogenic drivers that may be viable therapeutic targets. In initial screening studies, ROS1 and RET rearrangements were identified at similar frequencies (approximately 1%-2%), using a variety of genotyping techniques. Importantly, patients with either ROS1 or RET rearrangements appear to have unique clinical and pathologic features that may facilitate identification and enrichment strategies. These features may in turn expedite enrollment in clinical trials evaluating genotype-directed therapies in these rare patient populations. In this review, we summarize the molecular biology, clinical features, detection, and targeting of ROS1 and RET rearrangements in NSCLC. The Oncologist 2013;18:865-875 Implications for Practice: Treatment approaches for non-small cell lung cancer (NSCLC) have been advanced in recent years by the identification of distinct, molecularly-defined subsets of patients that derive benefit from targeted therapies. As a result, the field has placed greater focus on identifying new molecular targets. Recently, ROS1 and RET fusions were independently identified in 1%-2% of patients with NSCLC. Preclinical data and early clinical findings suggest that both may be viable therapeutic targets. In this review, we summarize this data as well as the clinical and pathologic features associated with these fusions. This may in turn inform screening strategies and the development of clinical trials evaluating genotype-driven therapies in these patient populations. INTRODUCTIONThe 2004 discovery that somatic mutations in the epidermal growth factor receptor (EGFR) confer sensitivity to EGFR tyrosine kinase inhibitors (TKIs) established a new treatment paradigm in non-small cell lung cancer (NSCLC) [1][2][3]. This discovery also placed greater focus on identifying new molecular subsets of NSCLC that may benefit from targeted therapies. In particular, emphasis has been placed on finding new "driver" oncogenes, so named because these genes are central to the growth and viability of cancer cells (e.g., mutant KRAS, BRAF, or HER2). Until recently, genetic alterations in NSCLC driver oncogenes were presumed to occur predominantly through point mutations or small insertions or deletions. Chromosomal translocations were thought to be infrequent events in solid tumors [4,5]. In 2007, however, Soda and colleagues discovered a novel fusion gene generated by a chromos...

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Section: Targeting Ros1mentioning

confidence: 99%

Novel Targets in Non-Small Cell Lung Cancer: ROS1 and RET Fusions

2013

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“…The tumor cells were stained positive by immunohistochemistry with an anti‐ROS1monoclonal antibody (clone D4D6, Cell Signaling Technology, Danvers, MA, USA, Fig ). We included our patient in a named patient access program for ROS1 mutation in pulmonary adenocarcinomas because of the promising results of a phase I study conducted with crizotinib in the United States . She was then treated with 250 mg of crizotinib twice daily from the beginning of September 2013.…”

Section: Case Descriptionmentioning

confidence: 99%

ROS1 mutation and treatment with crizotinib in a 30‐year old Caucasian woman with stage IV non‐small cell lung cancer/adenocarcinoma and complete remission

et al. 2014

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In this case report we describe a 30 year-old Caucasian woman with a histopathological diagnosis of pulmonary adenocarcinoma in both lungs with lipidic and micropapillary growth pattern and ROS1 (C-ros oncogene 1, receptor tyrosine kinase) rearrangement. There is evidence that crizotinib can be used for molecular target therapy in these patients. We enrolled the patient in an off-label program for the treatment of ROS1 rearranged adenocarcinomas with the EML4/anaplastic lymphoma kinase inhibitor crizotinib. After a follow-up of eight weeks we saw a complete remission in both lungs without any signs of metabolic tumor activity. This report shows the importance of testing young patients with adenocarcinomas of the lung for rare oncogenic driver mutations, such as ROS1, with possible molecular treatment options.

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“… 2 SCLC remains a biologically aggressive disease characterized by rapid tumor growth, a strong tendency for early widespread metastasis, and high genomic instability, 3 making it a formidable clinical challenge for the modern oncologist. The management of non-small-cell lung cancer (NSCLC) has been revolutionized with the advent of molecular profiling and the development of oncogene-driven therapies, 4 – 7 in addition to immunotherapy 8 ; however, progress in the treatment of SCLC over the decades has been more staggered.…”

Section: Introductionmentioning

confidence: 99%

Challenges and opportunities in the immunotherapy era: balancing expectations with hope in small-cell lung cancer

Khan,

Coleman

2024

Ther Adv Med Oncol

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Small-cell lung cancer (SCLC) is a biologically aggressive subtype of lung cancer, a lethal disease characterized by rapid tumor growth, early relapse, a strong tendency for early widespread metastasis, and high genomic instability, making it a formidable foe in modern oncology practice. While the management of non-SCLC has been revolutionized in the era of immunotherapy, progress in SCLC has been more muted. Recent randomized phase III clinical trials have combined programmed death ligand-1 inhibitors to a chemotherapy backbone and demonstrated improved survival; however, the absolute benefit observed is short months. There is an undeniable urgent need for better responses, better agents, novel therapeutic approaches, and more rational, biomarker-driven clinical trials in SCLC. In this review, we discuss the rationale and current understanding of the biology of SCLC in the modern era of immunotherapy, discuss recent advances in front-line immunotherapeutic approaches that have changed clinical practice globally, provide an overview of some of the challenges and limitations that have staggered immune checkpoint blockade in SCLC, and explore some of the novel immunotherapeutic approaches currently being investigated.

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Clinical Activity of Crizotinib in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) Harboring Ros1 Gene Rearrangement

Cited by 10 publications

References 16 publications

Novel Targets in Non-Small Cell Lung Cancer: ROS1 and RET Fusions

Novel Targets in Non-Small Cell Lung Cancer: ROS1 and RET Fusions

ROS1 mutation and treatment with crizotinib in a 30‐year old Caucasian woman with stage IV non‐small cell lung cancer/adenocarcinoma and complete remission

Challenges and opportunities in the immunotherapy era: balancing expectations with hope in small-cell lung cancer

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