#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Effects of Treatment with Crizotinib on Non-small Cell Lung Carcinoma with ALK Translocation in the Czech Republic


Authors: Pešek Miloš 1;  Skřičková Jana 2;  Kolek Vítězslav 3;  Šatánková Monika 2;  Koubková Leona 4;  Roubec Jaromír 5;  Chloupková Renata 6;  Černovská Markéta 7;  Benejová Andrea 2;  Kultan Juraj 3;  Hrnčiarik Michal 8;  Zemanová Milada 9;  Konečný Marek 6;  Čoupková Helena 10;  Svatoň Martin 1
Authors‘ workplace: Klinika pneumologie a ftizeologie, LF UK a FN Plzeň 1;  Klinika nemocí plicních a tuberkulózy LF MU a FN Brno 2;  Klinika nemocí plicních a tuberkulózy LF UP a FN Olomouc 3;  Pneumologická klinika 2. LF UK a FN Motol, Praha 4;  Klinika plicních nemocí a tuberkulózy LF OU a FN Ostrava 5;  Institut biostatistiky a analýz, LF MU, Brno 6;  Pneumologická klinika 1. LF UK a Thomayerova nemocnice, Praha 7;  Plicní klinika LF UK a FN Hradec Králové 8;  Onkologická klinika 1. LF UK a VFN v Praze 9;  Klinika komplexní onkologické péče, MOU, Brno 10
Published in: Klin Onkol 2018; 31(3): 207-212
Category: Original Articles
doi: https://doi.org/10.14735/amko2018207

Overview

Background:
Patients with advanced anaplastic lymphoma kinase (ALK) -positive non-small cell lung cancer (NSCLC) may gain significant benefit from treatment with the first-generation ALK inhibitor crizotinib. This study investigated the effects of crizotinib in advanced ALK-positive NSCLC patients via analyzing data submitted to the TULUNG registry by pneumo-oncology centers in the Czech Republic.

Patients and methods:
We analyzed the data of 60 NSCLC patients submitted to the TULUNG registry by pneumo-oncology centers who had ALK translocation confirmed by fluorescence in situ hybridization and complete data records from 2011 to 2017.

Results:
The median age of patients was 58 years. A total of 53% of patients were men, 90% had adenocarcinomas, 61.7% were smokers or ex-smokers, and 65% had a performance status of 0. Upon initiation of crizotinib therapy, most patients were at stage IV (88.3%) and the remainder were at stage IIIA or IIIB. Crizotinib was the second-line therapy in 71.7% of patients. A total of 20% of patients suffered side effects, while 11.7% suffered grade 3 and 4 adverse effects. A total of, 6.7, 25, 21.7, and 25% of patients displayed a complete response, a partial response, stable disease, and progressive disease, resp. Progression-free survival (PFS) was 5.8 months. Overall survival (OS) was 27.9 months from the initiation of the first-line therapy and 12.6 from the initiation of crizotinib therapy. PFS and OS were longer among nonsmokers and ex-smokers than among smokers (PFS, 9.7 vs. 5.8 vs. 3.8 months, p = 0.029; OS, 26.8 vs. 15.3 vs. 7.0 months, p = 0.015).

Conclusion:
Targeted crizotinib therapy is well tolerated and has significant benefit in patients with advanced ALK-positive NSCLC. Although international guidelines recommend that crizotinib is only used as a first-line therapy, it is used as a second-line and higher-line therapy in the Czech Republic. Clinical studies provide evidence that targeted therapy elicits better effects and less toxicity than routine chemotherapy.

Key words:
ALK translocation – crizotinib – targeted biological therapy – tyrosine kinase inhibitors

This work was supported by AZV grant No. 17- 30748A.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted: 17. 1. 2018

Accepted: 20. 2. 2018


Sources

1. Barlesi F, Mazieres J, Merlio JP et al. Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT). Lancet 2016; 387 (10026): 1415–1426. doi: 10.1016/S0140-6736 (16) 00004-0.

2. Lindeman NI, Cagle PT, Beasley MB et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Thorac Oncol 2013; 8 (7): 823–859. doi: 10.1097/JTO.0b013e318290868f.

3. Vidal J, Clavé S, de Muga S et al. Assessment of ALK status by FISH on 1000 Spanish non-small cell lung cancer patients. J Thorac Oncol 2014; 9 (12): 1816–1820. doi: 10.1097/JTO.0000000000000361.

4. Beržinec P, Kasan P, Plank L et al. Krizotinib v liečbe nemalobunkového karcinómu pľúc v Slovenskej republike. Studia pneumologica et phtiseologica 2017; 77 (4): 155–159.

5. 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. doi: 10.1016/S1470-2045 (12) 70344-3.

6. Novello S, Barlesi F, Califano R et al. Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2016; 27 (suppl 5): v1–v27. doi: 10.1093/annonc/mdw326.

7. Park K, Tan EH, O’Byrne K et al. Afatinib versus gefitinib as first-line treeatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol 2016; 17 (5): 577–589. doi: 10.1016/S1470-2045 (16) 300 33-X.

8. Rosell R, Moran T, Queralt C et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 2009; 361 (10): 958–967. doi: 10.1056/ NEJMoa0904554.

9. Johnson BE, Kris MG, Berry LD et al. A multicenter effort to identify driver mutations and employ targeted therapy in patients with lung adenocarcinomas: The Lung Cancer Mutation Consortium (LCMC). J Clin Oncol 2013; 31 (15 suppl): 8019. doi: 10.1200/jco.2013.31.15_suppl.8019.

10. Scarpinoa S, Rampioni Vinciguerra GL, Di Napoli A et al. High prevalence of ALK+/ROS1+ cases in pulmonary adenocarcinoma of adoloscents and young adults. Lung Cancer 2016; 97: 95–98. doi: 10.1016/j.lungcan.2016.04.022.

11. 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. doi: 10.1056/ NEJMoa1214886.

12. Solomon BJ, Mok T, Kim DW et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med 2014; 371 (23): 2167–2177. doi: 10.1056/ NEJMoa1408440.

13. Borghaei H, Paz-Ares L, Horn L et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 2015; 373 (17): 1627–1639. doi: 10.1056/NEJMoa1507643.

14. Fiala O, Pesek M, Skrickova J et al. Thyroid transcription factor 1 expression is associated with outcome of patients with non-squamous non-small cell lung cancer treated with pemetrexed-based chemotherapy. Tumour Biol 2017; 39 (2): 1010428317691186. doi: 10.1177/1010428317691186.

15. Reck M, Kaiser R, Mellemgaard A et al. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol 2014; 15 (2): 143–155. doi: 10.1016/S1470-2045 (13) 70586-2.

16. Kim DW, Mehra R, Tan DS et al. Activity and safety of ceritinib in patients with ALK-rearranged non-small-cell lung cancer (ASCEND-1): updated results from the multicentre, open-label, phase 1 trial. Lancet Oncol 2016; 17 (4): 452–463. doi: 10.1016/S1470-2045 (15) 00614-2.

17. Peters S, Camidge DR, Shaw AT et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med 2017; 377 (9): 829–838. doi: 10.1056/NEJMoa1704795.

18. Shaw AT, Gandhi L, Gadgeel S et al. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol 2016; 17 (2): 234–242. doi: 10.1016/S1470-2045 (15) 004 88-X.

19. Shaw AT, Kim DW, Mehra R, Tan DS et al. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med 2014; 370 (13): 1189–1197. doi: 10.1056/NEJMoa1311 107.

20. Aisner DL, Sholl LM, Berry L et al. The impact of smoking and TP53 mutations in lung adenocarcinoma patients with targetable mutations – the lung cancer mutation consortium (LCMC2). Clin Cancer Res 2017; 24 (5): 1038–1047. doi: 10.1158/1078-0432.CCR-17-2289.

21. Yang JCH, Ignatius SH, De Petris L et al. Pooled systemic efficacy and safety data from the Pivotal Phase II Studies (NP28673 and NP28761) of alectinib in ALK-positive non-small cell lung cancer. J Thorac Oncol 2017; 12 (10): 1552–1560. doi: 10.1016/j.jtho.2017.06.070.

Labels
Paediatric clinical oncology Surgery Clinical oncology
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#