CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2021; 42(01): 067-070
DOI: 10.1055/s-0041-1729728
Trainees’ Corner

ALK Inhibitors in Nonsmall Cell Lung Cancer

Nitish Garg
1   Vydehi Institute of Medical Sciences and Research Center, Bengaluru, Karnataka, India
,
Rushabh Kothari
2   Cancure Cancer Center, Narayana Multispeciality Hospital, Ahmedabad, Gujarat, India
› Institutsangaben

The management of advanced nonsmall cell lung cancer (NSCLC) has gone a definitive change over time with the discovery of small-molecule inhibitors. In 2004, the first initial description of actionable mutation of epidermal growth factor receptor (EGFR) was provided, and since then, almost 10 actionable mutations have been identified.[1] These include EGFR, anaplastic lymphoma kinase (ALK), ROS, MET, rearranged during transfection (RET), Kirsten rat sarcoma viral oncogene (KRAS), raf murine sarcoma virus oncogene homolog B (BRAF), and many others. After the development of the drugs against these receptors, these were approved by US Food and Drug Administration (FDA) for used against NSCLC with the receptor mutations.

The most common receptor tyrosine kinase mutations in adenocarcinoma lung are as follows:[2]

  1. KRAS mutation in 25% of cases of NSCLC

  2. EGFR mutation—10 to 30%

  3. MET amplification or MET exon 14 mutation—5%

  4. ALK mutation—3 to 7% cases

  5. BRAF mutations—2 to 4%

  6. Rest others: RET rearrangements, MEK1 mutation, FGFR1 amplification, Her2 mutation, ROS1 rearrangements, and NRAS mutation occur in 1% each

  7. The majority are still unknown—40%.

The drugs are very effective for patients with actionable mutant NSCLC with the response rates of 60 to 85% in the first-line setting. The main barrier is the development of resistance after a few months of treatment, which limits the duration of response to ~1 to 2 years for most of the drugs.[3]



Publikationsverlauf

Artikel online veröffentlicht:
28. Mai 2021

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  • References

  • 1 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
  • 2 Lin JJ, Shaw AT. Resisting resistance: targeted therapies in lung cancer. Trends Cancer 2016; 2 (07) 350-364
  • 3 Swanton C, Govindan R. Clinical implications of genomic discoveries in lung cancer. N Engl J Med 2016; 374 (19) 1864-1873
  • 4 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 (71/53) 561-566
  • 5 Rikova K, Guo A, Zeng Q. et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 2007; 131 (06) 1190-1203
  • 6 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 (09) 3143-3149
  • 7 Togashi Y, Soda M, Sakata S. et al. KLC1-ALK: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only. PLoS One 2012; 7 (02) e31323
  • 8 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
  • 9 Shackelford RE, Vora M, Mayhall K, Cotelingam J. ALK-rearrangements and testing methods in non-small cell lung cancer: a review. Genes Cancer 2014; 5 (1-2) 1-14
  • 10 Zanwar S, Noronha V, Joshi A. et al. Efficacy of crizotinib in ALK mutant non-small cell lung cancers that are positive by IHC but negative by FISH compared to FISH positive cases. Indian J Cancer 2017; 54 (04) 678-680
  • 11 Choi YL, Soda M, Yamashita Y. et al. ALK Lung Cancer Study Group. EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N Engl J Med 2010; 363 (18) 1734-1739
  • 12 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
  • 13 Solomon BJ, Bauer TM, Felip E. et al. Safety and efficacy of lorlatinib (PF-06463922) from the dose escalation component of a study in patients with advanced ALK+ or ROS1+ non-small cell lung cancer (NSCLC). J Clin Oncol 2016; 34 (Suppl. 01) 9009-9009
  • 14 Gainor JF, Dardaei L, Yoda S. et al. Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer. Cancer Discov 2016; 6 (10) 1118-1133
  • 15 Recondo G, Mezquita L, Facchinetti F. et al. Diverse resistance mechanisms to the third-generation ALK inhibitor lorlatinib in ALK-rearranged lung cancer. Clin Cancer Res 2020; 26 (01) 242-255
  • 16 Kim DW, Mehra R, Tan DSW. 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 (04) 452-463
  • 17 Solomon BJ, Mok T, Kim DW. et al. PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med 2014; 371 (23) 2167-2177
  • 18 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
  • 19 Cho BC, Kim DW, Bearz A. et al. ASCEND-8: A randomized phase 1 study of ceritinib, 450 mg or 600 mg, taken with a low-fat meal versus 750 mg in fasted state in patients with anaplastic lymphoma kinase (ALK)-rearranged metastatic non-small cell lung cancer (NSCLC). J Thorac Oncol 2017; 12 (09) 1357-1367
  • 20 Shaw AT, Kim DW, Mehra R. et al. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med 2014; 370 (13) 1189-1197
  • 21 Shaw AT, Kim TM, Crinò L. et al. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol 2017; 18 (07) 874-886
  • 22 Soria JC, Tan DSW, 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 (10/072) 917-929
  • 23 Shaw AT, Gandhi L, Gadgeel S. et al. study investigators. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol 2016; 17 (02) 234-242
  • 24 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 (07) 661-668
  • 25 Hida T, Nokihara H, Kondo M. et al. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet 2017; 390 (10/089) 29-39
  • 26 Kim DW, Tiseo M, Ahn MJ. et al. Brigatinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small-cell lung cancer: A randomized, multicenter phase ii trial. J Clin Oncol 2017; 35 (22) 2490-2498
  • 27 Kapoor A, Noronha V, Shetty O. et al. Molecular tumor board: case2- Evolution of resistance in anaplastic lymphoma kinase driven non-small cell lung carcinoma. Cancer Res Stat Treat 2020; 3: 89-92