#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Targeted therapy of non-small cell lung cancer


Authors: M. Svaton
Authors‘ workplace: Klinika pneumologie a ftizeologie LF UK v Plzni
Published in: Klin Onkol 2021; 34(Supplementum 1): 48-52
Category: Review
doi: https://doi.org/10.48095/ccko2021S48

Overview

The review article presents the current state and development of the treatment with tyrosine kinase inhibitors in advanced non-small cell lung cancer. It focuses on the therapeutic progress of traditionally targeted gene mutations EGFR, ALK and ROS1, as well as new established or promising targets. Mutations in the BRAF, NTRK, RET, cMET, HER2 and KRAS genes are discussed in this regard. In EGFR mutations, it focuses mainly on possible combination therapy and treatment for mutations in exon 20. In ALK translocation, it points to a new generation of tyrosine kinase inhibitors. In ROS1, the article mentions possible treatment in addition to the usual krizotinib, including the treatment after disease progression. For other genes, the author lists newly approved molecules, or molecules in the promising phase of their development.

Keywords:

Non-small cell lung cancer – targeted therapy – Tyrosine kinase inhibitors


Sources

1. Mok TS, Wu YL, Thongprasert S et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361 (10): 947–957. doi: 10.1056/ NEJMoa0810699.

2. Mok TS, Wu YL, Ahn MJ et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med 2017; 376 (7): 629–640. doi: 10.1056/NEJMoa1612674.

3. Ramalingam SS, Vansteenkiste J, Planchard D et al. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med 2020; 382 (1): 41–50. doi: 10.1056/NEJMoa1913662.

4. Soria JC, Ohe Y, Vansteenkiste J et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med 2018; 378 (2): 113–125. doi: 10.1056/NEJMoa1713137.

5. Paz-Ares L, Tan EH, O‘Byrne K et al. Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: overall survival data from the phase IIb LUX-Lung 7 trial. Ann Oncol 2017; 28 (2): 270–277. doi: 10.1093/annonc/mdw611.

6. Noronha V, Patil VM, Joshi A et al. Gefitinib versus gefitinib plus pemetrexed and carboplatin chemotherapy in EGFR-mutated lung cancer. J Clin Oncol 2020; 38 (2): 124–136. doi: 10.1200/JCO.19.01154.

7. Asahina H, Tanaka K, Morita S et al. A phase ii study of osimertinib combined with platinum plus pemetrexed in patients with EGFR-mutated advanced non-small-cell lung cancer: The OPAL study (NEJ032C/LOGIK1801). Clin Lung Cancer 2020; S1525-7304 (20) 30305-3. doi: 10.1016/j.cllc.2020.09.023.

8. Zhang L, Zhao H, Zhang Z et al. LBA50 ACTIVE: Apatinib plus gefitinib versus placebo plus gefitinib as first-line treatment for advanced epidermal growth factor receptor-mutant (EGFRm) non-small-cell lung cancer (NSCLC): a multicentered, randomized, double-blind, placebo–controlled phase III trial (CTONG1706). Ann Oncol 2020; 31 (Suppl 4): S1181.

9. Saito H, Fukuhara T, Furuya N et al. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol 2019; 20 (5): 625–635. doi: 10.1016/S1470-2045 (19) 30 035-X.

10. Landre T, Des Guetz G, Chouahnia K et al. First-line angiogenesis inhibitor plus erlotinib versus erlotinib alone for advanced non-small-cell lung cancer harboring an EGFR mutation. J Cancer Res Clin Oncol 2020; 146 (12): 3333–3339. doi: 10.1007/s00432-020- 03311-w.

11. Nakagawa K, Garon EB, Seto T et al. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2019; 20 (12): 1655–1669. doi: 10.1016/S1470-2045 (19) 30634-5.

12. Rotow JK, Costa DB, Paweletz CP et al. Concurrent osimertinib plus gefitinib for first-line treatment of EGFR-mutated non-small cell lung cancer (NSCLC). J Clin Oncol 2020; 38 (15_suppl): 9507–9507. doi: 10.1200/JCO.2020.38.15_suppl.9507.

13. Jänne PA, Neal JW, Camidge DR et al. Antitumor activity of TAK-788 in NSCLC with EGFR exon 20 insertions. J Clin Oncol 2019; 37 (Suppl 15): 9007. doi: 10.1200/JCO.2019.37.15_suppl.9007.

14. Wu YL, Tsuboi M, He J et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med 2020; 383 (18): 1711–1723. doi: 10.1056/NEJMoa202 7071.

15. 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.

16. Mok T, Camidge DR, Gadgeel SM et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol 2020; 31 (8): 1056–1064. doi: 10.1016/j.annonc.2020. 04.478.

17. Camidge DR, Kim HR, Ahn MJ et al. Brigatinib versus crizotinib in advanced ALK inhibitor-naive ALK-positive non-small cell lung cancer: second interim analysis of the phase III ALTA-1L trial. J Clin Oncol 2020; 38 (31): 3592–3603. doi: 10.1200/JCO.20.00505.

18. Selvaggi G, Wakelee HA, Mok T et al. Phase III randomized study of ensartinib vs crizotinib in anaplastic lymphoma kinase (ALK) positive NSCLC patients: eXalt3. J Thorac Oncol 2020; 15 (Suppl 10): E41–E42.

19. Shaw AT, Riely GJ, Bang YJ et al. Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001. Ann Oncol 2019; 30 (7): 1121–1126. doi: 10.1093/annonc/mdz131.

20. Michels S, Massuti B, Schildhaus HU et al. Safety and efficacy of crizotinib in patients with advanced or me­tastatic ROS1-rearranged lung cancer (EUCROSS): a European phase II clinical trial. J Thorac Oncol 2019; 14 (7): 1266–1276. doi: 10.1016/j.jtho.2019.03.020.

21. Lim SM, Kim HR, Lee JS et al. Open-label, multicenter, phase II study of ceritinib in patients with non-small-cell lung cancer harboring ROS1 rearrangement. J Clin Oncol 2017; 35 (23): 2613–2618. doi: 10.1200/JCO.2016.71. 3701.

22. Drilon A, Siena S, Dziadziuszko R et al. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1–2 trials. Lancet Oncol 2020; 21 (2): 261–270. doi: 10.1016/S1470-2045 (19) 306 90-4.

23. Chu QS. Targeting non-small cell lung cancer: driver mutation beyond epidermal growth factor mutation and anaplastic lymphoma kinase fusion. Ther Adv Med Oncol 2020; 12: 1758835919895756. doi: 10.1177/1758835919895756.

24. Shaw AT, Solomon BJ, Chiari R et al. Lorlatinib in advanced ROS1-positive non-small-cell lung cancer: a multicentre, open-label, single-arm, phase 1–2 trial. Lancet Oncol 2019; 20 (12): 1691–1701. doi: 10.1016/S1470-2045 (19) 30655-2.

25. Planchard D, Smit EF, Groen HJM et al. Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol 2017; 18 (10): 1307–1316. doi: 10.1016/S1470-2045 (17) 30679-4.

26. Negrao MV, Raymond VM, Lanman RB et al. Molecular landscape of BRAF-mutant NSCLC reveals an association between clonality and driver mutations and identifies targetable non-V600 driver mutations. J Thorac Oncol 2020; 15 (10): 1611–1623. doi: 10.1016/j.jtho.2020. 05.021.

27. Guisier F, Dubos-Arvis C, Vinas F et al. Efficacy and safety of anti-PD-1 immunotherapy in patients with advanced NSCLC with BRAF, HER2, or MET mutations or RET translocation: GFPC 01-2018. J Thorac Oncol 2020; 15 (4): 628–636. doi: 10.1016/j.jtho.2019.12.129.

28. Hong DS, DuBois SG, Kummar S et al. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol 2020; 21 (4): 531–540. doi: 10.1016/S1470-2045 (19) 30 856-3.

29. Doebele RC, Drilon A, Paz-Ares L et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1–2 trials. Lancet Oncol 2020; 21 (2): 271–282. doi: 10.1016/S1470-2045 (19) 30691-6.

30. Drilon A, Oxnard GR, Tan DSW et al. Efficacy of selpercatinib in RET fusion-positive non-small-cell lung cancer. N Engl J Med 2020; 383 (9): 813–824. doi: 10.1056/NEJMoa2005653.

31. Subbiah V, Hu M, Gainor J et al. Clinical activity of the RET inhibitor pralsetinib (BLU–667) in patients with RET fusion+ solid tumors. J Clin Oncol 2020; 38 (Suppl 15): 109. doi: 10.1200/JCO.2020.38.15_suppl.109.

32. Landi L, Chiari R, Tiseo M et al. Crizotinib in MET-deregulated or ROS1-rearranged pretreated non-small cell lung cancer (METROS): a phase II, prospective, multicenter, two-arms trial. Clin Cancer Res 2019; 25 (24): 7312–7319. doi: 10.1158/1078-0432.CCR-19-0994.

33. Moro-Sibilot D, Cozic N, Perol M et al. Crizotinib in c-MET- or ROS1-positive NSCLC: results of the AcSe phase II trial. Ann Oncol 2019; 30 (12): 1985–1991. doi: 10.1093/annonc/mdz407.

34. Paik PK, Felip E, Veillon R et al. Tepotinib in non-small-cell lung cancer with MET exon 14 skipping mutations. N Engl J Med 2020; 383 (10): 931–943. doi: 10.1056/NEJMoa2004407.

35. Wolf J, Seto T, Han JY et al. Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer. N Engl J Med 2020; 383 (10): 944–957. doi: 10.1056/NEJMoa2002787.

36. Liang H, Wang M. MET Oncogene in non-small cell lung cancer: mechanism of MET dysregulation and agents targeting the HGF/c-Met axis. Onco Targets Ther 2020; 13: 2491–2510. doi: 10.2147/OTT.S231 257.

37. Del Re M, Cucchiara F, Petrini I et al. erbB in NSCLC as a molecular target: current evidences and future directions. ESMO Open 2020; 5 (4): e000724. doi: 10.1136/esmoopen-2020-000724.

38. Rolfo C, Russo A. HER2 mutations in non-small cell lung cancer: a Herculean effort to hit the target. Cancer Discov 2020; 10 (5): 643–645. doi: 10.1158/2159-8290.CD-20-0225.

39. Ghimessy A, Radeczky P, Laszlo V et al. Current therapy of KRAS-mutant lung cancer. Cancer Metastasis Rev 2020; 39 (4): 1159–1177. doi: 10.1007/s10555-020-09903-9.

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#