Targeted Oncology

, Volume 12, Issue 6, pp 833–838 | Cite as

Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocations: Clinical Characteristics and Management in a Real-Life Setting: a French Retrospective Analysis (GFPC 02–14 Study)

  • Jean-Bernard Auliac
  • Isabelle Monnet
  • Catherine Dubos-Arvis
  • Anne Marie Chiappa
  • Nathalie Baize
  • Suzana Bota
  • Alain Vergnenegre
  • Helene Doubre
  • Chrystele Locher
  • Acya Bizieux
  • Gilles Robinet
  • Christos Chouaid
Short Communication



Chromosomal translocations involving the anaplastic lymphoma kinase gene (ALK) are rare oncogenic events found in 3–5% of non-small-cell lung cancers (NSCLC). Limited data have been published on the management of these patients outside clinical trials.


To investigate the clinical characteristics and management of patients with NSCLC harboring ALK translocations (ALK+) in a real-life setting in France.


This multicenter, observational, retrospective study included all NSCLC patients harboring ALK translocations diagnosed in participating centers between January 2012 and December 2014. Patient data include clinical characteristics, disease management, and outcomes [progression-free survival (PFS) and overall survival (OS)].


The 31 participating centers reported data on 132 patients, of whom 51% (n = 67) were male. The median age was 60.1 ± 14.5 (standard deviation) years; 89% (n = 106/119) had performance status 0/1 at diagnosis; 79% (n = 103/130) were non- or former smokers; 93% (n = 120/129) had adenocarcinomas and 74%(n = 97)/19%(n = 25)/7%(n = 10) had disease stages IV/III/I-II at diagnosis, respectively; co-mutations included EGFR (n = 2), BRAF (n  = 2), KRAS (n = 1), and HER2 (n = 1). Of the patients with stage IV NSCLC (n = 97), 96% received first-line treatment [75% chemotherapy-based, 21% ALK tyrosine kinase inhibitor (TKI)], with an associated response rate (RR), disease-control rate (DCR), and PFS of 42%, 64%, and 7.5 [95% confidence interval (CI) 5.9–9.5] months, respectively; 62% received second-line treatment (28% chemotherapy, 72% ALK TKI) with an associated RR, DCR, and PFS of 43.4%, 70%, and 4.7 (95% CI 4.0–8.1) months, respectively. The 2-year OS was 56.7% (95% CI 45.5–70.4%); median OS was not reached.


The results of this real-life analysis suggest that the prognosis of NSCLC patients with theALK translocation may be better than that of the overall NSCLC population, but the outcomes were poorer than those of ALK+ NSCLC patients included in clinical studies.


Compliance with Ethical Standards


The study was supported by academic grants from Lilly, Astra Zeneca, and Boehringer Ingelheim. The sponsors played no role in the design or performance of the study, data analysis, or manuscript preparation. The results belong to Groupe Français d’Oncologie Thoracique (GFPC). The data were analyzed by the GFPC statistician and interpreted by the authors.

Conflict of Interest

Jean-Bernard Auliac has received honoraria for attending scientific meetings, speaking, organizing research, or consulting from Boehringer Ingelheim, Hoffman-Roche, Lilly, and Pfizer. Helene Doubre has received honoraria for consulting from Novartis, AstraZeneca, BMS, MSD, and Boehringer Ingelheim. Christos Chouaid has received honoraria for attending scientific meetings, speaking, organizing research, or consulting from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Hoffman-Roche, Sanofi Aventis, Lilly, Novartis, and Amgen. All other authors declare no conflict of interest.


  1. 1.
    World Health Organization (WHO). Cancer. Fact sheet no. 297.
  2. 2.
    Barlesi F, Mazières J, Merlio JP, et al. Biomarkers France contributors. 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;387:1415–26.CrossRefPubMedGoogle Scholar
  3. 3.
    Soda M, Choi YL, Enomoto M. Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448:561–6.CrossRefPubMedGoogle Scholar
  4. 4.
    Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363:1693–703.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Shaw AT, Kim D-W, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368:2385–94.CrossRefPubMedGoogle Scholar
  6. 6.
    Solomon BJ, Mok T, Kim D-W, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371:2167–77.CrossRefPubMedGoogle Scholar
  7. 7.
    Shaw AT, Kim D-W, Mehra R, et al. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014;370:1189–97.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Gridelli C, de Marinis F, Cappuzzo F, et al. Treatment of advanced non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutation or ALK gene rearrangement: Results of an international expert panel meeting of the Italian Association of Thoracic Oncology. Clin Lung Cancer. 2014;15:173–81.CrossRefPubMedGoogle Scholar
  9. 9.
    Shaw AT, Yeap BY, Solomon BJ, et al. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: A retrospective analysis. Lancet Oncol. 2011;12:1004–12.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Camidge DR, Bang Y-J, Kwak EL, et al. Activity and safety of crizotinib in patients with ALK-positive non-mall-cell lung cancer: Updated results from a phase 1 study. Lancet Oncol. 2012;13:1011–9.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Ou SH, Ahn JS, De Petris L, et al. Alectinib in crizotinib-refractory ALK-rearranged non-small-cell lung cancer: A phase II global study. J Clin Oncol. 2016;34:661–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Soria JC, Tan DS, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017;389:917–29.CrossRefPubMedGoogle Scholar
  13. 13.
    Guerin A, Sasane M, Zhang J, et al. ALK-translocation testing and treatment patterns for patients with ALK-positive non-small cell lung cancer. Cancer Epidemiol. 2015;39:307–12.CrossRefPubMedGoogle Scholar
  14. 14.
    Cadranel J, Park K, Arrieta O, et al. Characteristics, treatment patterns, and survival among ALK+ non-small cell lung cancer (NSCLC) patients treated with crizotinib: A chart review study. Lung Cancer. 2016;98:9–14.CrossRefPubMedGoogle Scholar
  15. 15.
    Kayaniyil S, Hurry M, Wilson J, et al. Treatment patterns and survival in patients with ALK-positive non-small-cell lung cancer: A Canadian retrospective study. Curr Oncol. 2016;6:e589–97.CrossRefGoogle Scholar
  16. 16.
    Duruisseaux M, Besse B, Cadranel J, et al. Overall survival with crizotinib and next-generation ALK inhibitors in ALK-positive non-small-cell lung cancer (IFCT-1302 CLINALK): a French nationwide cohort retrospective study. Oncotarget. 2017;8(13):21903–17.Google Scholar
  17. 17.
    Guerin A, Sasane M, Wakelee H, et al. Treatment, overall survival, and costs in patients with ALK-positive non-small-cell lung cancer after crizotinib monotherapy. Curr Med Res Opin. 2015;31:1587–97.CrossRefPubMedGoogle Scholar
  18. 18.
    Yang P, Kulig K, Boland JM, et al. Worse disease-free survival in never-smokers with ALK+ lung adenocarcinoma. J Thorac Oncol. 2012;7:90–7.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Wang J, Cai Y, Dong Y, et al. Clinical characteristics and outcomes of patients with primary lung adenocarcinoma harboring ALK rearrangements detected by FISH, IHC, and RT-PCR. PLoS One. 2014;9:e101551.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    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;27:4247–53.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Shaw AT, Varghese AM, Solomon BJ, Costa DB, Novello S, Mino-Kenudson M, et al. Pemetrexed-based chemotherapy in patients with advanced, ALK-positive non-small cell lung cancer. Ann Oncol. 2013;24:59–66.CrossRefPubMedGoogle Scholar
  22. 22.
    Frampton JE. Crizotinib: A review of its use in the treatment of anaplastic lymphoma kinase-positive, advanced non-small cell lung cancer. Drugs. 2013;73:2031–51.CrossRefPubMedGoogle Scholar
  23. 23.
    Gainor JF, Varghese AM, Ou S-HI, et al. ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: An analysis of 1,683 patients with non-small cell lung cancer. Clin Cancer Res. 2013;15:4273–81.CrossRefGoogle Scholar
  24. 24.
    Lee T, Lee B, Choi YL, Han J, Ahn MJ, Um SW. Non-small cell lung cancer with concomitant EGFR, KRAS, and ALK mutations: Clinicopathologic features of 12 cases. J Pathol Transl Med. 2016;50:197–203.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Schmid S, Gautschi O, Rothschild S, et al. Clinical outcome of ALK-positive non-small cell lung cancer (NSCLC) patients with de novo EGFR or KRASco-mutations receiving tyrosine kinase inhibitors (TKIs). J Thorac Oncol. 2017;12(4):681–8.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Jean-Bernard Auliac
    • 1
  • Isabelle Monnet
    • 2
  • Catherine Dubos-Arvis
    • 3
  • Anne Marie Chiappa
    • 4
  • Nathalie Baize
    • 5
  • Suzana Bota
    • 6
  • Alain Vergnenegre
    • 7
  • Helene Doubre
    • 8
  • Chrystele Locher
    • 9
  • Acya Bizieux
    • 10
  • Gilles Robinet
    • 11
  • Christos Chouaid
    • 2
  1. 1.Service de Pneumologie et Oncologie ThoraciqueCenter Hospitalier (CH) François QuesnayMantes-la-JolieFrance
  2. 2.Centre Hospitalier Intercommunal de Créteil (CHI)CréteilFrance
  3. 3.CAC CaenCaenFrance
  4. 4.CH QuimperQuimperFrance
  5. 5.Le Centre Hospitalier Universitaire (CHU) AngersAngersFrance
  6. 6.CHU RouenRouenFrance
  7. 7.CHU LimogesLimogesFrance
  8. 8.CH SuresnesSuresnesFrance
  9. 9.CH MeauxMeauxFrance
  10. 10.CH La Roche-sur-YonLa Roche-sur-YonFrance
  11. 11.CHU BrestBrestFrance

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