Aan dit artikel is vele uren gewerkt. Opzoeken, vertalen, op de website plaatsen enz. Als u ons wilt ondersteunen dan kan dat via een al of niet anonieme donatie. Elk bedrag is welkom hoe klein ook. Klik hier als u ons wilt helpen kanker-actueel online te houden Wij zijn een ANBI organisatie en dus is uw donatie in principe aftrekbaar voor de belasting.

22 december 2014: aan onderstaand artikel kan ik deze publicatie in NEJM d.d. december 2014 toevoegen: 

Crizotinib was superior to standard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC. (Funded by Pfizer; PROFILE 1014 ClinicalTrials.gov number, NCT01154140.)

9 juli 2014: ik heb aan onderstaande informatie het abstract van het volledige studierapport: Development of anaplastic lymphoma kinase (ALK) inhibitors and molecular diagnosis in ALK rearrangement-positive lung cancer dat gratis is in te zien toegevoegd. Dit volledige studierapport geeft mooi overzicht van de aanpak van vormen van longkanker met ALK mutatie. Zie onderaan abstract met interessante referentielijst.

15 mei 2014: Lees ook artikel aanvullend op onderstaand artikel: 

De EORTC start een grote onafhankelijke studie naar genetische afwijkingen (receptoren afwijkingen en DNA mutaties) binnen wel of geen EGFR mutatie in relatie tot niet-kleincellige longkanker 

Afgelopen week bezocht ik een lezing van prof. dr. Bernards bij de KNAW over een kanker behandeling op maat en hij gebruikte crizotinib als voorbeeld van een succesvol medicijn dat op basis van een receptoren- en DNA onderzoek bij longkanker met ALK mutatie is ontwikkeld en voor hele goede resultaten zorgt bij longkankerpatiënten met de juiste mutatie. En vertelde ook hoe belangrijk het is om de EGFR mutatie te meten en de daaronder liggende andere mutaties en receptorenexpressie.

Pathways tumoren

1 oktober 2012: Bron: ESMO 2012

Crizotinib is superieur aan pemetrexed - Alimta of chemo - docetaxel bij gevorderde  niet-klein-cellige longkanker  stadium IIIB/IV met ALK positieve mutatie. Dit tonen de resultaten aan van een Fase III studie en werd gepresenteerd op ESMO 2012 in Wenen. Longartsen stellen dat crizotinib nu eerste lijns behandeling moet worden voor niet-klein-cellige longkanker met ALK positieve mutatie.

In deze studie met totaal 347 patiënten met niet-klein-cellige longkanker die allemaal eerder met chemo waren behandeld werd crizotinib vergeleken met op platina gebaseerde chemo plus pemetrexed - Alimta. Uit de studie kwam naar voren dat met name voor patiënten waarbij de ALK mutatie positief was getest crizotinib een hoog significante verbetering te zien gaf van de progressie vrije tijd en overall overlevingstijd en kwaliteit van leven.  Volgens de onderzoekers voldoet slechts 5% van de mensen met niet-klein-cellige longkanker aan een ALK positieve mutatie. Wat natuurlijk niet wegneemt dat als u tot die groep behoort er een nieuwe mogelijkheid is.tot behandeling. Klik hier voor meer informatie over crizotinib, zoals bijwerkingen enz.

De gerandomiseerde fase III studie vergeleek de werkzaamheid en veiligheid van crizotinib met standaard chemotherapie met pemetrexed - Alimta of docetaxel, in 347 patiënten met ALK-positieve, stadium IIIB / IV niet-klein-cellige longkanker (NSCLC) die reeds eerder waren behandeld met chemotherapie.
De groep die crizotinib kreeg had een significant langere progressievrije overleving met mediaan 7,7 maanden in vergelijking tot 3,0 maanden bij patiënten die alleen chemo hadden ontvangen
(HR 0,49, 95% CI 0,37-0.64, p <0,0001). Het totale respons percentage was ook significant hoger bij patiënten behandeld met crizotinib (65% vs 20%, p <0,0001).

Over de totale overleving is nog geen onderbouwde conclusie te trekken omdat de studie nog loopt en het eind van de studie nog niet is bereikt. Maar er is op dit moment al een significante cross-over in de studie gezien waarin de patiënten die als eerste werden ingedeeld in de chemogroep en ziekte progressie lieten zien en daarna naar de crizotinib groep mochten overstappen. Vandaar dat ook een meerderheid van de patiënten uit de chemogroep ook in feite crizotinib hebben gekregen en dit maakt de bepaling van de totale overleving ingewikkeld.
Duur van de behandeling was langer voor crizotinib waarmee gemiddeld 11 cycli werden gegeven in vergelijking met 4 cycli met pemetrexed - Alimta of docetaxel. Ook dit geeft aan dat crizotinib veruit superieur was aan chemo plus Alimta of chemo alleen.

De meest voorkomende behandeling gerelateerde bijwerkingen met crizotinib werden gemeld door 59% van de patiënten, 53% meldden diarree, 52% misselijkheid, braken 44% en 36% van de
patiënten verhoogde transaminasen (giststof).   Bijwerkingen, waaronder misselijkheid, vermoeidheid, neutropenie, verminderde eetlust, en haaruitval werden gemeld door 35%, 29% 22% 21% en 20%
van de patiënten die pemetrexed - Alimta of docetaxel hadden ontvangen. Alle behandelgroepen hadden dezelfde incidentie van graad 3/4 behandeling gerelateerde bijwerkingen van 31%. Zes procent van crizotinib patiënten in vergelijking met 10% van pemetrexed / docetaxel patiënten stopten met het onderzoek vanwege de behandeling gerelateerde bijwerkingen. Echter, ondanks de bijwerkingen, rapporteerden de patiënten nog steeds verbeterde kwaliteit van leven met crizotinib in vergelijking met chemo.

Conclusie gebaseerd op dit onderzoek is dat na de wereldwijde implementatie van gerichte therapie bij longkanker patiënten gedefinieerd door EGFR-mutatie (Tarceva - Iressa zijn de meest gebruikte medicijnen darvoor), dit de tweede groep is van patiënten met niet-kleincellige longkanker  die duidelijk baat hebben bij een behandeling die direct gericht is op een moleculaire verandering. De resultaten van dit onderzoek is  een belangrijke stap naar meer geïndividualiseerde therapie bij longkankerpatiënten, aldus aanwezige longspecialiste in Wenen.

Hier het abstract van deze studie zoals gepresenteerd in Wenen en waaruit bovenstaand artikel is samengesteld.

Phase III trial shows crizotinib superior to single-agent chemotherapy for ALK-positive advanced NSCLC

30.09.12
Category: Vienna 2012 Congress, Vienna 2012 App
Crizotinib superior to pemetrexed or docetaxel in the first head-to-head comparison study

The results of a new phase III trial show that crizotinib is more effective treatment than standard chemotherapy for patients with advanced, ALK-positive non-small cell lung cancer (NSCLC), who have been previously treated with first-line, platinum-based chemotherapy. The study results are reported at the ESMO 2012 Congress of the European Society for Medical Oncology in Vienna.

Rearrangements of the anaplastic lymphoma kinase (ALK) gene are found in about 5% of all NSCLC. In previous studies, crizotinib has been shown to induce significant clinical responses in patients with advanced ALK-positive NSCLC, but this is the first phase III study in this setting.  

This study is also the first head-to-head comparison of crizotinib with standard chemotherapy and according to the lead study author, Dr Alice Shaw from Massachusetts General Hospital Cancer Center, Boston, USA, crizotinib is superior to standard single-agent chemotherapy in terms of response, progression-free survival and quality of life in ALK-positive patients who have been previously treated with first-line, platinum-based chemotherapy. These results establish crizotinib as the standard of care for patients with advanced, previously treated, ALK-positive NSCLC.

The current global randomized phase III study compared the efficacy and safety of crizotinib with standard chemotherapy with pemetrexed or docetaxel, in 347 patients with ALK-positive, stage IIIB/IV NSCLC who had already been treated with chemotherapy.

The study showed that crizotinib prolonged progression-free survival to a median of 7.7 months compared to 3.0 months among those patients who received the chemotherapy (HR 0.49; 95% CI 0.37–0.64; p < 0.0001). The overall response rate was also significantly higher in those treated with crizotinib (65% vs 20%; p < 0.0001). So far, the analysis of the overall survival rate with the two drugs is still immature, and there are no enough events to draw meaningful conclusions.

There was significant crossover in the study, patients who were randomized to receive chemotherapy and had disease progression were allowed to crossover to receive crizotinib. Hence, the majority of patients on the chemotherapy arm actually did receive crizotinib and this makes determination of overall survival benefit very challenging. Duration of treatment was longer for crizotinib where a median of 11 cycles compared to 4 with pemetrexed or docetaxel were started by patients.

The most common treatment-related adverse events with crizotinib were reported by 59% of patients, 53% diarrhea, 52% had nausea, 44% vomiting and 36% of patients reported elevated transaminases. Adverse events including nausea, fatigue, neutropenia, decreased appetite, and alopecia were reported by 35%, 29% 22% 21% and 20% of patients receiving pemetrexed or docetaxel. All treatment groups had the same incidence of grade 3/4 treatment related adverse events of 31%. Six percent of crizotinib patients compared to 10% of pemetrexed/docetaxel patients discontinued the trial due to treatment related adverse events. However, despite side effects, patients still reported improved quality of life on crizotinib compared with chemotherapy.

Commenting on clinical relevance of these data, Dr Enriqueta Felip, Head of the Lung Cancer Unit in Oncology Department at Vall d'Hebron University Hospital in Barcelona, Spain, and chair of the ESMO 2012 Metastatic NSCLC program track (who was not involved in the study) said that crizotinib, an oral drug, is more effective than standard chemotherapy in previously treated patients with advanced NSCLC with a specific molecular alteration, ALK. This is the first randomized study in this group of patients selected precisely because they have ALK-positive tumors.

After the worldwide implementation of targeted therapy in lung cancer patients defined by EGFR mutation, this is the second group of patients with non-small cell lung cancer to clearly benefit from a therapy directly targeting a molecular alteration. The results of this study represent a significant step towards more individualized therapy in lung cancer patients.

The improvement and validation of methods for the detection of ALK rearrangement in NSCLC patients will be key to the optimal clinical use of ALK inhibitors.

Onco Targets Ther. 2014; 7: 375–385.
Published online Mar 5, 2014. doi:  10.2147/OTT.S38868
PMCID: PMC3949762

Development of anaplastic lymphoma kinase (ALK) inhibitors and molecular diagnosis in ALK rearrangement-positive lung cancer

Abstract

The fusion of echinoderm microtubule-associated protein-like 4 with anaplastic lymphoma kinase (ALK) was identified as a transforming gene for lung cancer in 2007. This genetic rearrangement accounts for 2%–5% of non-small-cell lung cancer (NSCLC) cases, occurring predominantly in younger individuals with adenocarcinoma who are never- or light smokers. A small-molecule tyrosine-kinase inhibitor of ALK, crizotinib, was rapidly approved by the US Food and Drug Administration on the basis of its pronounced clinical activity in patients with ALK rearrangement-positive NSCLC. Next-generation ALK inhibitors, such as alectinib, LDK378, and AP26113, are also being developed in ongoing clinical trials. In addition, the improvement and validation of methods for the detection of ALK rearrangement in NSCLC patients will be key to the optimal clinical use of ALK inhibitors. We here summarize recent progress in the development of new ALK inhibitors and in the molecular diagnosis of ALK rearrangement-positive NSCLC.

References

1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893–2917. [PubMed]
2. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350(21):2129–2139. [PubMed]
3. Sordella R, Bell DW, Haber DA, Settleman J. Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science. 2004;305(5687):1163–1167. [PubMed]
4. Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362(25):2380–2388. [PubMed]
5. Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010;11(2):121–128. [PubMed]
6. Le Beau MM, Bitter MA, Larson RA, et al. The t(2;5)(p23;q35): a recurring chromosomal abnormality in ki-1-positive anaplastic large cell lymphoma. Leukemia. Dec. 1989;3(12):866–870. [PubMed]
7. Morris SW, Kirstein MN, Valentine MB, et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin’s lymphoma. Science. 1994;263(5151):1281–1284. [PubMed]
8. Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448(7153):561–566. [PubMed]
9. Shaw AT, Yeap BY, Mino-Kenudson M, et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol. 2009;27(26):4247–4253. [PMC free article] [PubMed]
10. Camidge DR, Kono SA, Flacco A, et al. Optimizing the detection of lung cancer patients harboring anaplastic lymphoma kinase (ALK) gene rearrangements potentially suitable for ALK inhibitor treatment. Clin Cancer Res. 2010;16(22):5581–5590. [PMC free article] [PubMed]
11. Choi YL, Takeuchi K, Soda M, et al. Identification of novel isoforms of the EML4-ALK transforming gene in non-small cell lung cancer. Cancer Res. 2008;68(13):4971–4976. [PubMed]
12. Sasaki T, Rodig SJ, Chirieac LR, Janne PA. The biology and treatment of EML4-ALK non-small cell lung cancer. Eur J Cancer. 2010;46(10):1773–1780. [PMC free article] [PubMed]
13. Mano H. Non-solid oncogenes in solid tumors: EML4-ALK fusion genes in lung cancer. Cancer Sci. 2008;99(12):2349–2355. [PubMed]
14. Soda M, Takada S, Takeuchi K, et al. A mouse model for EML4-ALK-positive lung cancer. Proc Natl Acad Sci U S A. 2008;105(50):19893–19897. [PMC free article] [PubMed]
15. McDermott U, Iafrate AJ, Gray NS, et al. Genomic alterations of anaplastic lymphoma kinase may sensitize tumors to anaplastic lymphoma kinase inhibitors. Cancer Res. 2008;68(9):3389–3395. [PubMed]
16. Takezawa K, Okamoto I, Nishio K, Janne PA, Nakagawa K. Role of ERK-BIM and STAT3-survivin signaling pathways in ALK inhibitor-induced apoptosis in EML4-ALK-positive lung cancer. Clin Cancer Res. 2011;17(8):2140–2148. [PubMed]
17. Okamoto I, Nakagawa K. Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase-targeted therapy for advanced non-small cell lung cancer: molecular and clinical aspects. Cancer Sci. 2012;103(8):1391–1396. [PubMed]
18. Koivunen JP, Mermel C, Zejnullahu K, et al. EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Clin Cancer Res. 2008;14(13):4275–4283. [PMC free article] [PubMed]
19. Christensen JG, Zou HY, Arango ME, et al. Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-met, in experimental models of anaplastic large-cell lymphoma. Mol Cancer Ther. 2007;6(12 Pt 1):3314–3322. [PubMed]
20. Zou HY, Li Q, Lee JH, et al. An orally available small-molecule inhibitor of c-met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms. Cancer Res. 2007;67(9):4408–4417. [PubMed]
21. Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363(18):1693–1703. [PMC free article] [PubMed]
22. Camidge DR, Bang YJ, Kwak EL, et al. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol. 2012;13(10):1011–1019. [PMC free article] [PubMed]
23. Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368(25):2385–2394. [PubMed]
24. Takeda M, Okamoto I, Sakai K, Kawakami H, Nishio K, Nakagawa K. Clinical outcome for EML4-ALK-positive patients with advanced non-small-cell lung cancer treated with first-line platinum-based chemotherapy. Ann Oncol. 2012;23(11):2931–2936. [PubMed]
25. Pfizer A Clinical Trial Testing The Efficacy Of Crizotinib Versus Standard Chemotherapy Pemetrexed Plus Cisplatin Or Carboplatin In Patients With ALK Positive Non Squamous Cancer Of The Lung (PROFILE 1014) [Accessed January 21, 2014]. Available from: http://clinicaltrials.gov/show/NCT01154140. NLM identifier: NCT01154140.
26. Tamiya A, Okamoto I, Miyazaki M, Shimizu S, Kitaichi M, Nakagawa K. Severe acute interstitial lung disease after crizotinib therapy in a patient with EML4-ALK-positive non-small-cell lung cancer. J Clin Oncol. 2013;31(1):e15–e17. [PubMed]
27. Doebele RC, Pilling AB, Aisner DL, et al. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res. 2012;18(5):1472–1482. [PMC free article] [PubMed]
28. Zhang S, Wang F, Keats J, et al. Crizotinib-resistant mutants of EML4-ALK identified through an accelerated mutagenesis screen. Chem Biol Drug Des. 2011;78(6):999–1005. [PMC free article] [PubMed]
29. Sasaki T, Koivunen J, Ogino A, et al. A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors. Cancer Res. 2011;71(18):6051–6060. [PMC free article] [PubMed]
30. Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med. 2012;4(120):120ra17. [PMC free article] [PubMed]
31. Tanizaki J, Okamoto I, Okabe T, et al. Activation of HER family signaling as a mechanism of acquired resistance to ALK inhibitors in EML4-ALK-positive non-small cell lung cancer. Clin Cancer Res. 2012;18(22):6219–6226. [PubMed]
32. Choi YL, Soda M, Yamashita Y, et al. EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N Engl J Med. 2010;363(18):1734–1739. [PubMed]
33. Heuckmann JM, Holzel M, Sos ML, et al. ALK mutations conferring differential resistance to structurally diverse ALK inhibitors. Clin Cancer Res. 2011;17(23):7394–7401. [PMC free article] [PubMed]
34. Sequist LV, Waltman BA, Dias-Santagata D, et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med. 2011;3(75):75ra26. [PMC free article] [PubMed]
35. Balak MN, Gong Y, Riely GJ, et al. Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clin Cancer Res. 2006;12(21):6494–6501. [PubMed]
36. Yu HA, Arcila ME, Rekhtman N, et al. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res. 2013;19(8):2240–2247. [PMC free article] [PubMed]
37. Sakamoto H, Tsukaguchi T, Hiroshima S, et al. CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell. 2011;19(5):679–690. [PubMed]
38. Seto T, Kiura K, Nishio M, et al. CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): a single-arm, open-label, phase 1–2 study. Lancet Oncol. 2013;14(7):590–598. [PubMed]
39. Chugai Pharmaceutical Co., Ltd Open-label randomized PhaseIII Study of the Efficacy and Safety of CH5424802(AF802) in ALK-Positive Advanced or Recurrecnt Non-Small Cell Lung Cancer with Crizotinib control. [Accessed January 21, 2014]. Available from: http://www.clinicaltrials.jp/user/showCteDetailE.jsp?japicId=JapicCTI-132316. Identifier: JapicCTI-132316.
40. Ou S, Gadgeel S, Chiappori A, et al. Late breaking abstract: Safety and efficacy analysis of RO5424802/CH5424802 in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) patients who have failed crizotinib in a dose-finding Phase I study; Presented at: ECCO/ESMO; September 30, 2013; Amsterdam.
41. Hoffmann-La Roche A Study of RO5424802 in Patients With Non-Small Cell Lung Cancer Who Have ALK Mutation and Failed Crizotinib Treatment. [Accessed January 21, 2014]. Available from: http://clinicaltrials.gov/show/NCT01801111. NLM identifier: NCT01801111.
42. Marsilje TH, Pei W, Chen B, et al. Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulf onyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. J Med Chem. 2013 Jun 26; Epub. [PubMed]
43. Shaw AT, Mehra R, Kim DW, et al. Clinical activity of the ALK inhibitor LDK378 in advanced, ALK positive NSCLC. J Clin Oncol. 2013;31(Suppl):8010.
44. Novartis Pharmaceuticals LDK378 Versus Chemotherapy in ALK Rearranged (ALK Positive) Patients Previously Treated With Chemotherapy (Platinum Doublet) and Crizotinib. [Accessed January 21, 2014]. Available from: http://clinicaltrials.gov/show/NCT01828112. NLM identifier: NCT01828112.
45. Novartis Pharmaceuticals LDK378 Versus Chemotherapy in Previously Untreated Patients With ALK Rearranged Non-small Cell Lung Cancer. [Accessed January 21, 2014]. Available from: http://clinicaltrials.gov/show/NCT01828099. NLM identifier: NCT01828099.
46. Katayama R, Khan TM, Benes C, et al. Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc Natl Acad Sci U S A. 2011;108(18):7535–7540. [PMC free article] [PubMed]
47. Camidge DR, Bazhenova L, Salgia R, et al. First-in-human dose-finding study of the ALK/EGFR inhibitor AP26113 in patients with advanced malignancies: updated results. J Clin Oncol. 2013;31(Suppl):8031.
48. Chihara D, Suzuki R. More on crizotinib. N Engl J Med. 2011;364(8):776–777. author reply 778. [PubMed]
49. Martelli MP, Sozzi G, Hernandez L, et al. EML4-ALK rearrangement in non-small cell lung cancer and non-tumor lung tissues. Am J Pathol. 2009;174(2):661–670. [PMC free article] [PubMed]
50. Takeuchi K, Choi YL, Togashi Y, et al. KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer. Clin Cancer Res. 2009;15(9):3143–3149. [PubMed]
51. Han XH, Zhang NN, Ma L, et al. Immunohistochemistry reliably detects ALK rearrangements in patients with advanced non-small-cell lung cancer. Virchows Arch. 2013;463(4):583–591. [PubMed]
52. Li Y, Pan Y, Wang R, et al. ALK-rearranged lung cancer in Chinese: a comprehensive assessment of clinicopathology, IHC, FISH and RT-PCR. PLoS One. 2013;8(7):e69016. [PMC free article] [PubMed]
53. Ying J, Guo L, Qiu T, et al. Diagnostic value of a novel fully automated immunochemistry assay for detection of ALK rearrangement in primary lung adenocarcinoma. Ann Oncol. 2013;24(10):2589–2593. [PubMed]
54. Selinger CI, Rogers TM, Russell PA, et al. Testing for ALK rearrangement in lung adenocarcinoma: a multicenter comparison of immunohistochemistry and fluorescent in situ hybridization. Mod Pathol. 2013;26(12):1545–1553. [PubMed]
55. To KF, Tong JH, Yeung KS, et al. Detection of ALK rearrangement by immunohistochemistry in lung adenocarcinoma and the identification of a novel EML4-ALK variant. J Thorac Oncol. 2013;8(7):883–891. [PubMed]
56. Sholl LM, Weremowicz S, Gray SW, et al. Combined use of ALK immunohistochemistry and FISH for optimal detection of ALK-rearranged lung adenocarcinomas. J Thorac Oncol. 2013;8(3):322–328. [PMC free article] [PubMed]
57. Park HS, Lee JK, Kim DW, et al. Immunohistochemical screening for anaplastic lymphoma kinase (ALK) rearrangement in advanced non-small cell lung cancer patients. Lung Cancer. 2012;77(2):288–292. [PubMed]
58. Yi ES, Boland JM, Maleszewski JJ, et al. Correlation of IHC and FISH for ALK gene rearrangement in non-small cell lung carcinoma: IHC score algorithm for FISH. J Thorac Oncol. 2011;6(3):459–465. [PubMed]
59. Mino-Kenudson M, Chirieac LR, Law K, et al. A novel, highly sensitive antibody allows for the routine detection of ALK-rearranged lung adenocarcinomas by standard immunohistochemistry. Clin Cancer Res. 2010;16(5):1561–1571. [PMC free article] [PubMed]
60. Wallander ML, Geiersbach KB, Tripp SR, Layfield LJ. Comparison of reverse transcription-polymerase chain reaction, immunohistochemistry, and fluorescence in situ hybridization methodologies for detection of echinoderm microtubule-associated proteinlike 4-anaplastic lymphoma kinase fusion-positive non-small cell lung carcinoma: implications for optimal clinical testing. Arch Pathol Lab Med. 2012;136(7):796–803. [PubMed]
61. Wu YC, Chang IC, Wang CL, et al. Comparison of IHC, FISH and RT-PCR methods for detection of ALK rearrangements in 312 non-small cell lung cancer patients in Taiwan. PLoS One. 2013;8(8):e70839. [PMC free article] [PubMed]
62. Takeuchi K, Choi YL, Soda M, et al. Multiplex reverse transcription-PCR screening for EML4-ALK fusion transcripts. Clin Cancer Res. 2008;14(20):6618–6624. [PubMed]
63. Sakai K, Okamoto I, Takezawa K, et al. A novel mass spectrometry-based assay for diagnosis of EML4-ALK-positive non-small cell lung cancer. J Thorac Oncol. 2012;7(5):913–918. [PubMed]
64. Astellas Pharma Inc Study of an Investigational Drug, ASP3026, in Patients With Solid Tumors. [Accessed January 21, 2014]. Available from: http://clinicaltrials.gov/show/NCT01401504. NLM identifier: NCT01401504.
65. Xcovery Holding, Company LLC. Phase 1 Safety Study of X-396, an Oral ALK Inhibitor, in Patients With Advanced Solid Tumors. [Accessed January 21, 2014]. Available from: http://clinicaltrials.gov/show/NCT01625234. NLM identifier: NCT01625234.
66. Teva Branded Pharmaceutical Products, R&D Inc To Determine the Maximum Tolerated Dose of Oral CEP-37440 in Patients With Advanced or Metastatic Solid Tumors. [Accessed January 21, 2014]. Available from: http://clinicaltrials.gov/show/NCT01922752. NLM identifier: NCT01922752.

Plaats een reactie ...

Reageer op "Longkanker: Crizotinib is superieur aan pemetrexed - Alimta of chemo - docetaxel bij niet-klein-cellige longkanker met ALK positieve genmutatie copy 1"


Gerelateerde artikelen
 

Gerelateerde artikelen

Longkanker: Combinatiebehandeling >> Longkanker: Selpercatinib >> Longkanker: Biomarker test >> Longkanker: EORTC opent grote >> Longkanker: Crizotinib is >> Longkanker: Crizotinib en >> Longkanker: Immuuntherapie >>