The role of multidisciplinary team and molecular tumor board in the treatment of a patient with lung cancer

Česká verzia

Authors: P. Grell; S. Bořilová; O. Bílek; I. Kiss
Authors place of work: Klinika komplexní péče LF MU a MOÚ Brno
Published in the journal: Klin Onkol 2021; 34(Supplementum 1): 20-28
Category: Review
doi: https://doi.org/10.48095/ccko2021S20

Summary

Nowadays, selection of appropriate therapy in patients with lung cancer is based on comprehensive molecular characteristics of their tumors. On molecular level, lung cancer is one of the best described solid tumors. Currently, there are already methods in routine clinical practice that enable a relatively quick, accurate and cost-effective analysis of dozens of genes and thus make it possible to determine a complex molecular characteristic of a tumor. This creates new possibilities to tailor the treatment to the patients to achieve long-term survival with a good quality of life. New technologies bring more and more information and to transform it into the best clinical benefit for the patient can be challenging. This is a place for the multidisciplinary approach in the form of a molecular tumor board. Its role is to try to indicate appropriate therapy based on the identified genetic alteration. Today, dozens of targeted drugs are available and new treatment options are emerging even for genetic alterations, which until now seemed to be undruggable.

Keywords:

lung cancer – comprehensive molecular profiling – molecular tumor board – precision oncology – targeted therapy

Zdroje

1. Mosele F, Remon J, Mateo J et al. Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group. Ann Oncol 2020; 31 (11): 1491–1505. doi: 10.1016/j.annonc.2020.07.014.

2. Leighl, N, et al. Abstract 4460: Clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in newly diagnosed metastatic non-small cell lung cancer. Clin Cancer Res 2049; 25 (15): 4671–4700. doi: 10.1158/1078-0432.CCR-19-0624.

3. Hochmair MJ, Buder A, Schwab S et al. Liquid-biopsy- -based identification of EGFR T790M mutation-mediated resistance to afatinib treatment in patients with advanced EGFR mutation-positive NSCLC, and subsequent response to osimertinib. Target Oncol 14 (1): 75–83. doi: 10.1007/s11523-018-0612-z.

4. Dagogo-Jack I, Rose Branon A, Ferris LA et al. Tracking the evolution of resistance to ALK tyrosine kinase inhibitors through longitudinal analysis of circulating tumor DNA. JCO Precis Oncol 2018; 2018: PO.17.00160. doi: 10.1200/PO.17.00160.

5. Rolfo C, Russo A. Liquid biopsy for early stage lung cancer moves ever closer. Nat Rev Clin Oncol 2020; 17 (9): 523–524. doi: 10.1038/s41571-020-0393-z.

6. Cargnin S, Canonico PL, Genazzani AA et al. Quantitative analysis of circulating cell-free DNA for correlation with lung cancer survival: a systematic review and meta--analysis. J Thorac Oncol 2017; 12 (1): 43–53. doi: 10.1016/j.jtho.2016.08.002.

7. Akamatsu H, Koh Y, Okamoto I et al. Clinical significance of monitoring EGFR mutation in plasma using multiplexed digital PCR in EGFR mutated patients treated with afatinib (West Japan Oncology Group 8114LTR study). Lung Cancer 20189; 131: 128–133. doi: 10.1016/j.lungcan.2019.03.021.

8. Westphalen BC, Bokemeyer C, Büttner R et al. Conceptual framework for precision cancer medicine in Germany: consensus statement of the Deutsche Krebshilfe working group ‘Molecular Diagnostics and Therapy’. Eur J Cancer 2020; 135: 1–7. doi: 10.1016/j.ejca.2020.04.019.

9. Mateo J, Chakravarty D, Denstmann R et al. A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). Ann Oncol 2018; 29 (9): 1895–1902. doi: 10.1093/annonc/mdy263.

10. https: //www.oncokb.org/.

11. https: //www.mycancergenome.org/.

12. https: //genie.cbioportal.org/login.jsp.

13. Trédan O, Wang Q, Pissaloux D et al. Molecular screening program to select molecular-based recommended therapies for metastatic cancer patients: analysis from the ProfiLER trial. Ann Oncol 2019; 30 (5): 757–765. doi: 10.1093/annonc/mdz080.

14. Le Tourneau C, Delord J-P, Gonçalves A et al. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol 2015; 16 (13): 1324–1334. doi: 10.1016/S1470-2045 (15) 00188-6.

15. Massard C, Michiels S, Ferté C et al. High-throughput genomics and clinical outcome in hard-to-treat advanced cancers: results of the MOSCATO 01 trial. Cancer Discov 2017; 7 (6): 586–595. doi: 10.1158/2159-8290.CD-16-1396.

16. Flaherty KT, Gray R, Chen A et al. The molecular analysis for therapy choice (NCI-MATCH) trial: lessons for genomic trial design. JNCI J Natl Cancer Inst 2020; 112 (10): 1021–1029. doi: 10.1093/jnci/djz245.

17. Hoes LR et al. 594P the drug rediscovery protocol (DRUP): results of the first 500 treated patients. [online]. Available from: https: //www.annalsofoncology.org/article/S0923-7534 (20) 40704-5/fulltext.

18. Mangat PK, Halabi S, Bruinooge SS et al. Rationale and design of the targeted agent and profiling utilization registry study. JCO Precis Oncol 2018; 2018: 10.1200/PO.18.00122. doi: 10.1200/PO.18.00122.

19. Fisher JG, Tait D, Garrett-Mayer E et al. Cetuximab in patients with breast cancer, non-small cell lung cancer, and ovarian cancer without KRAS, NRAS, or BRAF mutations: results from the targeted agent and profiling utilization registry (TAPUR) study. Target Oncol 2020; 15 (6): 733–741. doi: 10.1007/s11523-020-00753-7.

20. Ahn ER, Mangat PK, Garret-Mayer E et al. Palbociclib in patients with non–small-cell lung cancer with CDKN2A alterations: results from the targeted agent and profiling utilization registry study. JCO Precis Oncol 2020; 4: 757–766. doi: 10.1200/PO.20.00037.

21. Middleton G, Fletcher P, Popat S et al. The National Lung Matrix Trial of personalized therapy in lung cancer. Nature 2020; 583 (7818): 807–812. doi: 10.1038/s41586-020-2481-8.

22. 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. doi: 10.1056/NEJMoa040938.

23. Paez JG, Jänne PA, Lee JC et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004; 304 (5676): 1497–1500. doi: 10.1126/science.1099314.

24. Barlesi F, Mazieres J, Merlio J-P 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.

25. Litvak AM, Paik PK, Woo KM et al. Clinical characteristics and course of 63 patients with BRAF mutant lung cancers. J Thorac Oncol 2014; 9 (11): 1669–1674. doi: 10.1097/JTO.0000000000000344.

26. Tissot C, Couraud S, Tanguy R et al. Clinical characteristics and outcome of patients with lung cancer harboring BRAF mutations. Lung Cancer 2016; 91: 23–28. doi: 10.1016/j.lungcan.2015.11.006.

27. Davies H, Bignell GR, Cox C et al. Mutations of the BRAF gene in human cancer. Nature 2002; 417 (6892): 949–954. doi: 10.1038/nature00766.

28. Paik PK, Arcila ME, Fara M et al. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol 2011; 29 (15): 2046–2051. doi: 10.1200/JCO.2010.33.1280.

29. Marchetti A, Felicioni L, Malatesta S et al. Clinical features and outcome of patients with non–small-cell lung cancer harboring BRAF mutations. J Clin Oncol 2011; 29 (26): 3574–3579. doi: 10.1200/JCO.2011.35.9638.

30. Cardarella S, Ogino A, Nishino M et al. Clinical, pathologic, and biologic features associated with BRAF mutations in non-small cell lung cancer. Clin Cancer Res 2013; 19 (16): 4532–4540. doi: 10.1158/1078-0432.CCR-13-0657.

31. Garnett MJ, Marais R. Guilty as charged: B-RAF is a human oncogene. Cancer Cell 2004; 6 (4): 313–319. doi: 10.1016/j.ccr.2004.09.022.

32. Brustugun OT, et al. BRAF-mutations in non-small cell lung cancer. Lung Cancer 2014; 84 (1): 36–38.

33. Hyman DM, Puzanov I, Subbiah V et al. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med 2015; 373 (8): 726–736. doi: 10.1056/NEJMoa1502309.

34. Mazieres J, Cropet C, Montané L et al. Vemurafenib in non-small-cell lung cancer patients with BRAFV600 and BRAFnonV600 mutations. Ann Oncol 2020; 31 (2): 289–294. doi: 10.1016/j.annonc.2019.10.022.

35. Planchard D, Besse B, Groen HJ et al. Dabrafenib plus trametinib in patients with previously treated BRAF (V600E) -mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol 2016; 17 (7): 984–993. doi: 10.1016/S1470-2045 (16) 30146-2.

36. Planchard D, Smit EF, Groen HJ 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: 1307–1316. doi: 10.1016/S1470-2045 (17) 30679-4.

37. Planchard D, et al. Dabrafenib in patients with BRAF (V600E) -positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. Lancet Oncol 2016; 17 (5): 642–650. doi: 10.1016/S1470-2045 (16) 00077-2.

38. Sholl LM, et al. Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: the lung cancer mutation consortium experience. J Thorac Oncol 2015; 10 (5): 768–777. doi: 10.1097/JTO.0000000000000516.

39. Slebos RJ, Kibbelaar RE, Dalesio O et al. K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung. N Engl J Med 1990; 323: 561–565. doi: 10.1056/NEJM199008303230902.

40. Riely G J, Marks J, Pao W. KRAS mutations in non-small cell lung cancer. Proc Am. Thorac Soc 2008; 6 (2): 201–205.

41. Dogan S, Shen R, Ang DC et al. Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: higher susceptibility of women to smoking-related KRAS-mutant cancers. Clin. Cancer Res 2012; 18 (22): 6169–6177. doi: 10.1158/1078-0432.CCR-11-3265.

42. O’Bryan JP. Pharmacological targeting of RAS: recent success with direct inhibitors. Pharmacol Res 2019; 139: 503–511. doi: 10.1016/j.phrs.2018.10.021.

43. Jänne PA, Shaw AT, Pereira JR et al. Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study. Lancet Oncol 2013; 14: 38–47. doi: 10.1016/S1470-2045 (12) 70489-8.

44. Jänne PA, van den Heuvel MM, Barlesi F et al. Selumetinib plus docetaxel compared with docetaxel alone and progression-free survival in patients with KRAS-mutant advanced non–small cell lung cancer: the SELECT-1 randomized clinical trial. JAMA 2017; 317 (18): 1844–1853. doi: 10.1001/jama.2017.3438.

45. Paz-Ares L, Hirsh V, Zhang L et al. Monotherapy administration of sorafenib in patients with non–small cell lung cancer (MISSION) trial. J Thorac Oncol 2015; 10: 1745–1753. doi: 10.1097/JTO.0000000000000693.

46. Kim ES, Herbst RS, Wistuba II et al. The BATTLE trial: personalizing therapy for lung cancer. Cancer Discov 2011; 1: 44–53. doi: 10.1158/2159-8274.CD-10-0010.

47. Goldman JW, Mazieres J, Barlesi F et al. A randomized phase 3 study of abemaciclib versus erlotinib in previously treated patients with stage IV NSCLC with KRAS mutation: JUNIPER. J Clin Oncol 2018; 36 (15): 9025–9025.

48. Hong DS, et al. KRASG12C inhibition with sotorasib in advanced solid tumors. N Engl J Med 2020; 383: 1207–1217. doi: 10.1056/NEJMoa1917239.

49. Dana-Farber Cancer Institute. Targeted inhibitor of mutated KRAS gene shows promise in early trial for lung, bowel, and other solid tumors. [online]. Available from: https: //www.dana-farber.org/newsroom/news-releases/2020/targeted-inhibitor-of-mutated-kras-gene-shows-promise-in-early-trial-for-lung--bowel--and-other-solid-tumors/.

50. Nikiforov YE. RET/PTC rearrangement in thyroid tumors. Endocr Pathol 2002; 13 (1): 13–16. doi: 10.1385/ep: 13: 1: 03.

51. Ju YS, Lee W-C, Shin J-Y et al. A transforming KIF5B and RET gene fusion in lung adenocarcinoma revealed from whole-genome and transcriptome sequencing. Genome Res 2012; 22 (3): 436–445. doi: 10.1101/gr.133645.111.

52. Kohno T, Ichikawa H, Totoki Y et al. KIF5B-RET fusions in lung adenocarcinoma. Nat Med 2012; 18 (3): 375–377. doi: 10.1038/nm.2644.

53. Ackermann CJ, Stock G, Tay R et al. Targeted therapy for ret-rearranged non-small cell lung cancer: clinical development and future directions. OncoTargets Ther 2019; 12: 7857–7864. doi: 10.2147/OTT.S171665.

54. Drilon A, Oxnard GR, Tan DS 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.

55. Gainor JF, Lee DH, Curigliano G et al. Clinical activity and tolerability of BLU-667, a highly potent and selective RET inhibitor, in patients (pts) with advanced RET-fusion+ non-small cell lung cancer (NSCLC). J Clin Oncol 2019; 37: 9008–9008.

56. Drilon A, Fu S, Patel MR et al. A Phase I/Ib trial of the VEGFR-sparing multikinase RET inhibitor RXDX-105. Cancer Discov 2019; 9 (3): 384–395. doi: 10.1158/2159-8290.CD-18-0839.

57. Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature 2014; 511 (7511): 543–550. doi: 10.1038/nature 13385.

58. Seo JS, Ju YS, Lee W-C et al. The transcriptional landscape and mutational profile of lung adenocarcinoma. Genome Res 2012; 22: 2109–2119. doi: 10.1101/gr.145144. 112.

59. Lee GD, Lee SE, Oh D-Y et al. MET exon 14 skipping mutations in lung adenocarcinoma: clinicopathologic implications and prognostic values. J Thorac Oncol 2017; 12 (8): 1233–1246. doi: 10.1016/j.jtho.2017.04.031.

60. Drilon AE, Camidge DR, Ou SH et al. Efficacy and safety of crizotinib in patients (pts) with advanced MET exon 14-altered non-small cell lung cancer (NSCLC). J Clin Oncol 2016; 34 (15): 108–108.

61. Wang SX, Zhang BM, Wakelee HA et al. Case series of MET exon 14 skipping mutation-positive non-small-cell lung cancers with response to crizotinib and cabozantinib. Anticancer Drugs 2019; 30 (5): 537–541. doi: 10.1097/CAD.0000000000000765.

62. Wolf J, Seto T, Han J-Y et al. Capmatinib (INC280) in METex14-mutated advanced non-small cell lung cancer (NSCLC): efficacy data from the phase II GEOMETRY mono-1 study. J Clin Oncol 2019; 37 (15): 9004.

63. 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.

64. Lu S, Fang J, Li X et al. Phase II study of savolitinib in patients (pts) with pulmonary sarcomatoid carcinoma (PSC) and other types of non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations (METex14+). J Clin Oncol 2020; 38 (15): 9519–9519.

65. Li BT, Ross DS, Aisner DL et al. HER2 amplification and HER2 mutation are distinct molecular targets in lung cancers. J Thorac Oncol 2016; 11 (3): 414–419. doi: 10.1016/j.jtho.2015.10.025.

66. Mazières J, Peters S, Lepage B et al. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J Clin Oncol 2013; 31: 1997–2003. doi: 10.1200/JCO.2012.45.6095.

67. Stephens P, Hunter C, Bignell G et al. Lung cancer: intragenic ERBB2 kinase mutations in tumours. Nature 2004; 431 (7008): 525–526. doi: 10.1038/431525b.

68. Buttitta F, Barassi F, Fresu G et al. Mutational analysis of the HER2 gene in lung tumors from Caucasian patients: mutations are mainly present in adenocarcinomas with bronchioloalveolar features. Int J Cancer 2006; 119 (11): 2586–2591. doi: 10.1002/ijc.22143.

69. Arcila ME, Chaft JE, Nafa K et al. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin Cancer Res 2012; 18 (18): 4910–4918. doi: 10.1158/1078-0432.CCR-12-0912.

70. Krug LM, Miller VA, Patel J et al. Randomized phase II study of weekly docetaxel plus trastuzumab versus weekly paclitaxel plus trastuzumab in patients with previously untreated advanced nonsmall cell lung carcinoma. Cancer 2005; 104 (10): 2149–2155. doi: 10.1002/cncr.21 428.

71. Gatzemeier U, et al. Randomized phase II trial of gemcitabine-cisplatin with or without trastuzumab in HER2--positive non-small-cell lung cancer. Ann Oncol 2004; 15 (1): 19–27. doi: 10.1093/annonc/mdh031.

72. Herbst RS, Davies AM, Natale RB et al. Efficacy and safety of single-agent pertuzumab, a human epidermal receptor dimerization inhibitor, in patients with non small cell lung cancer. Clin Cancer Res 2007; 13 (20): 6175–6181. doi: 10.1158/1078-0432.CCR-07-0460.

73. Hughes B, Mileshkin L, Townley P et al. Pertuzumab and erlotinib in patients with relapsed non-small cell lung cancer: a phase II study using 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging. The Oncologist 2014; 19 (2): 175–176. doi: 10.1634/theoncologist.2013-0026.

74. Hainsworth JD, Meric-Bernstam F, Swanton C et al. Targeted therapy for advanced solid tumors on the basis of molecular profiles: results from my pathway, an open-label, phase IIa multiple basket study. J Clin Oncol 2018; 36 (6): 536–542. doi: 10.1200/JCO.2017.75.3 780.

75. Li BT, Shen R, Buonocore D et al. Ado-trastuzumab emtansine for patients with HER2-mutant lung cancers: results from a phase II basket trial. J Clin Oncol 2018; 36 (24): 2532–2537. doi: 10.1200/JCO.2018.77.9777.

76. Peters S, Stahel R, Bubendorf L et al. Trastuzumab emtansine (T-DM1) in patients with previously treated HER2-overexpressing metastatic non-small cell lung cancer: efficacy, safety, and biomarkers. Clin Cancer Res 2019; 25 (1): 64–72. doi: 10.1158/1078-0432.CCR-18-1 590.

77. Smit EF, Nakagawa K, Nagasaka M et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-mutated metastatic non-small cell lung cancer (NSCLC): interim results of DESTINY-Lung01. J Clin Oncol 2020; 38 (15): 9504–9504.

78. Dziadziuszko R, Smit EF, Dafni U et al. Afatinib in NSCLC with HER2 mutations: results of the prospective, open-label phase II NICHE trial of European Thoracic Oncology Platform (ETOP). J Thorac Oncol 2019; 14 (6): 1086–1094. doi: 10.1016/j.jtho.2019.02.017.

79. Kris MG, Camidge DR, Giaccone G et al. Targeting HER2 aberrations as actionable drivers in lung cancers: phase II trial of the pan-HER tyrosine kinase inhibitor dacomitinib in patients with HER2-mutant or amplified tumors. Ann Oncol 2015; 26 (7): 1421–1427. doi: 10.1093/annonc/mdv186.

80. Gandhi L, Besse B, Mazieres J et al. MA04.02 neratinib ± temsirolimus in HER2-mutant lung cancers: an international, randomized phase II study. J Thorac Oncol 2017; 12 (1): S358–S359.

81. Socinski MA, Cornelissen R, Garassino MC et al. LBA60 ZENITH20, a multinational, multi-cohort phase II study of poziotinib in NSCLC patients with EGFR or HER2 exon 20 insertion mutations. Ann Oncol 2020; 31 (4): S1188.

82. Wang Y, Jiang T, Qin Z et al. HER2 exon 20 insertions in non-small-cell lung cancer are sensitive to the irreversible pan-HER receptor tyrosine kinase inhibitor pyrotinib. Ann Oncol 2019; 30 (3): 447–455. doi: 10.1093/annonc/mdy542.

83. Farago AF, Tylor MS, Doebele RC et al. Clinicopathologic features of non–small-cell lung cancer harboring an NTRK gene fusion. JCO Precis Oncol 2018; 2018: PO.18.00037. doi: 10.1200/PO.18.00037.

84. Marchetti A, Felicioni L, Pelosi G et al. Frequent mutations in the neurotrophic tyrosine receptor kinase gene family in large cell neuroendocrine carcinoma of the lung. Hum Mutat 2008; 29 (5): 609–616. doi: 10.1002/humu.20707.

85. Drilon A, Laetsch TW, Kummar S et al. Efficacy of larotrectinib in TRK fusion–positive cancers in adults and children. N Engl J Med 2018; 378 (8): 731–739. doi: 10.1056/NEJMoa1714448.

86. Drilon A, Kummar S, Moreno V et al. Activity of larotrectinib in TRK fusion lung cancer. Ann Oncol 2019; 30 (2): ii48–ii49.

87. Paz-Ares L, Doebele RC, Farago AF et al. Entrectinib in NTRK fusion-positive non-small cell lung cancer (NSCLC): integrated analysis of patients (pts) enrolled in STARTRK-2, STARTRK-1 and ALKA-372-001. Ann Oncol 2019; 30 (2): ii48–ii49.