Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. patients with recurrent, ALK-positive non-small cell lung cancer (NSCLC). A prior phase III study showed that second-line treatment with crizotinib a small-molecule inhibitor of ALK, MET, and ROS1 kinase was more effective than chemotherapy in patients with ALK-positive non-small-cell lung cancer (NSCLC; N Engl J Med 2013; 368:2385. opens in new tab). Results of PROFILE 1029, a phase III comparison of first-line crizotinib versus chemotherapy in east asian patients with ALK-positive advanced non-small cell lung cancer. N Engl J Med. Crizotinib versus platinum-based double-agent chemotherapy as the first line treatment in advanced anaplastic lymphoma kinase-positive lung adenocarcinoma. Daum G, Eisenmann-Tappe I, Fries HW, Kim DW, Tiseo M, Ahn MJ, Reckamp KL, Hansen KH, Kim SW, et al. Only a decade ago chemotherapy was the standard first-line treatment for all lung cancer (even with ALK because there was no testing done). The response rates were 65% (95% CI, 58 to 72) with crizotinib, as compared with 20% (95% CI, 14 to 26) with chemotherapy (P<0.001). Findings This randomized clinical phase 3 trial including 290 patients met the primary end point; the median progression-free survival was statistically significantly longer with ensartinib than with crizotinib (25.8 vs 12.7 months), and the confirmed intracranial response rate was 64% with ensartinib vs 21% with crizotinib for patients with . 2016; 5 (6):1013-1021. Solomon BJ, Mok T, Kim DW, et al. By Benjamin J. Solomon, Tony Mok, Dong-Wan Kim, Yi-Long Wu, Kazuhiko Nakagawa, Tarek Mekhail, Enriqueta Felip, Federico Cappuzzo, Jolanda Paolini, Tiziana Usari, Shrividya Iyer, Arlene Reisman, Keith D. Wilner, Jennifer Tursi and Fiona Blackhall Earlier results from the ongoing PROFILE 1014 trial showed that crizotinib offers better progression-free survival (PFS) and response rates . N Engl J . 2013;368:2385-2394. Solomon BJ, Mok T, Kim DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. 15. Approval of Lorbrena was based on a subgroup of 215 patients with ALK-positive metastatic NSCLC who were previously treated with one or more ALK kinase inhibitors. 2014; 371 . Here, we report the final overall survival (OS) results. N Engl J Med. 2018 Oct;13(10):1539-1548. doi: 10.1016/j.jtho.2018.06.012. 9. DOI: 10.1056/NEJMoa1408440 Corpus ID: 11369952. 2014;371(23):2167-2177. doi: 10.1056/NEJMoa1408440 PubMed Google Scholar Crossref 27. First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer. N Engl J Med. Purpose The phase III PROFILE 1014 trial compared crizotinib with chemotherapy as first-line treatment in patients with anaplastic lymphoma kinase (ALK) -positive advanced nonsquamous non-small-cell lung cancer. In the United States, pembrolizumab is the emerging standard of care for the initial treatment of patients with advanced non-small cell lung cancer whose tumors express programmed death ligand 1 in at least of 50% of cells on the basis of the results of the KEYNOTE 024 trial. Lancet 2017 , 389 , 917-929. First-line crizotinib significantly improved PFS, objective response rate, and patient-reported outcomes compared with standard platinum-based chemotherapy in East Asian patients with ALK-positive advanced NSCLC, which is similar to the results from PROFILE 1014. 2018 Aug 1;36(22):2251-2258. doi: 10.1200/JCO.2017.77.4794. CONCLUSIONS: Crizotinib was superior to standard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC. N Engl J Med 2013;368:2385-94. 1 Peters S. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. No abstract available. Solomon B, Bauer TM, De Marinis F, et al. Shaw AT, Kim DW, Nakagawa K, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. Study of TQ-B3139 Versus Crizotinib in the First Line Treatment of Subjects With Anaplastic Lymphoma Kinase (ALK) Positive Non-Small Cell Lung Cancer (NSCLC) The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. A retrospective study of Chinese patients. Background: The efficacy of the ALK inhibitor crizotinib as compared with standard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer (NSCLC) is unknown. Patients and Methods Patients were randomly assigned to receive oral crizotinib 250 mg twice daily (n = 172) or intravenous . N Engl J Med . Cui S, Zhao Y, Dong L, et al. . 16. N Engl J Med 2014;371:2167-77. Lorlatinib, a 3rd-generation ALK inhibitor, significantly prolonged progression-free survival (PFS) vs crizotinib in the CROWN trial in patients with untreated ALK-positive non-small cell lung cancer (NSCLC). First-line crizotinib versus chemotherapy in ALK-positive lung cancer Benjamin J Solomon, Tony Mok, Dong-Wan Kim, Yi-Long Wu, Kazuhiko Nakagawa, Tarek Mekhail, Enriqueta Felip, Federico Cappuzzo, Jolanda Paolini, Tiziana Usari, Shrividya Iyer, Arlene Reisman, Keith D Wilner, Jennifer Tursi, Fiona Blackhall As compared with chemotherapy, crizotinib was associated with greater reduction in lung cancer symptoms and greater improvement in quality of life. Brigatinib was first approved in the US in 2017 as a treatment for ALK-positive, metastatic NSCLC patients who had progressed on or were intolerant to crizotinib (Pfizer's Xalkori). New Engl J Med 2014;371:2167-77. Here, we report the nal overall survival (OS) results. 1 INTRODUCTION. Only after the discovery of the ALK gene and its linkage to an inhibitor, Crizotinib, in 2011, did the first line treatment for lung cancer patients with an ALK mutation change to Crizotinib. First-Line Crizotinib Versus Chemotherapy in ALK-Positive Lung Cancer. [Google Scholar] First-line crizotinib versus chemotherapy in ALK-positive lung cancer. The efficacy of lorlatinib, as compared with that of crizotinib, as first-line treatment for advanced ALK-positive NSCLC is unclear. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. J Clin Oncol 2018:Jco2017774794. 2014;371:2167-2177. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. 2014; 371: 2167-77. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. Lorlatinib vs crizotinib in the first-line treatment of patients (pts) with advanced ALK-positive non-small cell lung cancer (NSCLC): Results of the phase . 2 Soria JC, Tan DSW, Chiari R, et al. To my mind, it does translate to it becoming a first line treatment option for patients with untreated ALK positive metastatic non-small cell lung cancer. Here, we report the final overall survival (OS) results. For decades, chemotherapy has remained the standard of care for advanced NSCLC. Ceritinib provides longer progression-free survival than chemotherapy in crizotinib-pre-treated patients with non-small-cell lung cancer harbouring an ALK rearrangement, according to results of . First-line crizotinib therapy offered better intracranial disease control rate (IC-DCR) than chemotherapy in patients with ALK-positive non-small-cell lung cancer (NSCLC) and stable treated brain metastases, according to results of a phase III study.. N Engl J . Lorlatinib, a third-generation inhibitor of anaplastic lymphoma kinase (ALK), has antitumor activity in previously treated patients with ALK-positive non-small-cell lung cancer (NSCLC). Between 3 percent and 5 percent of metastatic NSCLC patients harbor ALK rearrangements. 2014 Dec 4;371(23):2167-77. pmid:25470694 . N Engl J Med . BackgroundThe efficacy of the ALK inhibitor crizotinib as compared with standard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer (NSCLC) is unknown. Although crizotinib was the standard first-line therapy for advanced ALK-positive NSCLC 3 when the CROWN trial was initiated in 2017, it has now been supplanted by more potent second-generation . Wu YL, et al. Crizotinib versus chemotherapy in asian patients with alk-positive advanced non-small cell lung cancer Makoto Nishio, Dong Wan Kim , Yi Long Wu, Kazuhiko Nakagawa, Benjamin J. Solomon, Alice T. Shaw, Satoshi Hashigaki, Emiko Ohki, Tiziana Usari, Jolanda Paolini, Anna Polli, Keith D. Wilner, Tony Mok We report data from the Asian subgroup of CROWN. We know that patients with CNS metastases have inferior outcomes in general with ALK positive disease and so therefore having intracranial control is really quite important. Treating ALKpositive lung cancer - early successes and future . FDA approval: ceritinib for the treatment of metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer. N Engl J Med 2014; 371 . [ Google Scholar ] [ CrossRef ] EML4-ALK positive lung cancer is a primary malignant lung tumor whose cells contain a characteristic abnormal configuration of DNA wherein the echinoderm . The ALEX study demonstrated significantly improved progression-free survival (PFS) with alectinib versus crizotinib in treatment-naive ALK-positive non-small-cell lung cancer (NSCLC) at the primary data cut-off (9 February 2017).We report mature PFS (cut-off: 30 November 2018) and overall survival (OS) data up to 5 years (cut-off: 29 November 2019). N Engl J Med. These results, which will be presented at the . CONCLUSIONS: Crizotinib was superior to standard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC. . J Clin Oncol. . Final Overall Survival Analysis From a Study Comparing First-Line Crizotinib Versus Chemotherapy in ALK-Mutation-Positive Non-Small-Cell Lung Cancer. . First-line crizotinib versus chemotherapy in ALK-positive lung cancer Benjamin J. Solomon, Tony Mok, Dong Wan Kim , Yi Long Wu, Kazuhiko Nakagawa, Tarek Mekhail, Enriqueta Felip, Federico Cappuzzo, Jolanda Paolini, Tiziana Usari, Shrividya Iyer, Arlene Reisman, Keith D. Wilner, Jennifer Tursi, Fiona Blackhall But obviously there are comparative studies of brigatinib versus the crizotinib, which is the ALTA first line study, as well as the ALEX study that compared alectinib with the crizotinib. Cancer Med. Patients and Methods Patients were randomly assigned to receive oral crizotinib . ROS1 rearrangement (ROS1+) is an actionable driver mutation that occurs in 1% to 2% of patients with non-small-cell lung cancer (NSCLC). Methods We conducted an open-label, phase 3 trial comparing crizotinib with chemotherapy in 343 patients with advanced ALK-positive nonsquamous NSCLC who had . N Engl J Med 2014; 371:2167-77. As a first-line treatment, crizotinib (Xalkori) improved progression-free survival (PFS) and objective response rate (ORR) compared with standard chemotherapy in patients with advanced ALK . First-line crizotinib versus chemotherapy in ALK-positive lung cancer N Engl J Med , 371 ( 2014 ) , pp. The primary purpose of this study is to evaluate the efficacy and safety of X-396 (ensartinib) vs. crizotinib in patients with ALK-positive non-small cell lung cancer that have received up to 1 prior chemotherapy regimen and no prior ALK inhibitor. This indication . Shaw AT, Kim DW, Nakagawa K, et al. phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). J Thorac Oncol. One patient did not follow medical advice and reduced 5 Solomon BJ, Mok T, Kim DW et al. Standard first-line therapy for advanced, ALK-positive non-small-cell lung cancer is the multitargeted ALK/ROS1/MET inhibitor, crizotinib,1,2 followed by more potent second-generation . DOI: 10.1056/NEJMx150034. The overall response rate to Lorbrena treatment was 48%, with 4% complete and 44% partial responses. Final overall survival analysis from a study comparing first-line crizotinib versus chemotherapy in ALK-mutation-positive non-small-cell lung cancer. Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, et al. Is there a progression-free survival benefit of first-line crizotinib versus standard chemotherapy and second-line crizotinib in ALK-positive advanced lung adenocarcinoma? First-line ceritinib versus platinum-based chemotherapy in advanced ALKrearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Results of PROFILE 1029, a Phase III Comparison of First-Line Crizotinib versus Chemotherapy in East Asian Patients with ALK-Positive Advanced Non-Small Cell Lung Cancer. Clin Cancer Res 2015;21:2436-9. The New England journal of medicine. N Engl J Med (2014) 371:2167-77. doi: 10.1056/NEJMoa1408440. Solomon BJ, Mok T, Kim D-W, Wu Y-L, Nakagawa K, Mekhail T, et al. The efficacy of the ALK inhibitor crizotinib as compared with standard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer (NSCLC) is unknown. 2017;377:829-38 . Solomon BJ, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, et al. 2167 - 2177 CrossRef View Record in Scopus Google Scholar BACKGROUND The efficacy of the ALK inhibitor crizotinib as compared with standard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer (NSCLC) is unknown. Advanced non-small cell lung cancer Laboratory confirmed anaplastic lymphoma kinase (ALK)-positive tumour defined as either IHC 3+ or FISH positive ECOG 0-2 Second-line monotherapy for disease progression after prior platinum-based chemotherapy NOTE: Patients must have progressive disease on or after first -line therapy Background: To compare the efficacy of crizotinib, pemetrexed and other chemotherapy regimens as a first-line treatment in patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in real world clinical use and to evaluate the +86-571-87,236,876 predictive clinical factors of the efficacy of crizotinib. @article{Solomon2014FirstlineCV, title={First-line crizotinib versus chemotherapy in ALK-positive lung cancer. The J-ALEX trial was a phase III, open-label study comparing two anaplastic lymphoma kinase (ALK) inhibitors crizotinib, the current standard first-line therapy for non-small-cell lung cancer (NSCLC), and alectinib in 207 Japanese ALK-inhibitor-naive patients with ALK-positive NSCLC.Patients either had not received chemotherapy or had received a single regimen. As compared with chemotherapy, crizotinib was associated with greater reduction in lung cancer symptoms and greater improvement in quality of life. Solomon BJ, Kim DW, Wu YL, et al. Introduction. }, author={B. Solomon and T. Mok and Dong-Wan Kim and Yi-Long Wu and K. Nakagawa and T. Mekhail and E. Felip and F. Cappuzzo and J. Paolini and T. Usari and S. Iyer .
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