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Role of Anti-EGFR Targeted Therapies in Stage III Locally Advanced Non-small Cell Lung Cancer: Give or Not to Give?

  • Lung Cancer (H Borghaei, Section Editor)
  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Identification of targetable mutations such as EGFR has allowed opportunity for Tyrosine Kinase Inhibitor (TKI) therapy for lung cancer treatment. EGFR-TKIs have revolutionized treatment of advanced EGFR mutant Non-Small Cell Lung Cancer (NSCLC), but there is little evidence that EGFR-TKI treatment is effective in stage III NSCLC. Here we discuss recent evidence supporting the use of EGFR-TKI therapy in combination with chemotherapy and radiation in stage III NSCLC.

Recent Findings

Recent results of small trials testing EGFR-TKI therapy in combination with chemoradiation showed promising efficacy, improved outcomes, and a tolerable toxicity profile when administered to patients with EGFR mutant stage III NSCLC. However, strong supporting evidence regarding EGFR-TKI therapy in stage III NSCLC is lacking because previous trials involved a small patient population or were terminated due to slow participant accrual.

Summary

Despite the lack of large randomized clinical trials, results from early-stage trials highlight promising future directions for investigating the use of EGFR-TKI therapy in stage III NSCLC treatment.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Torre LA, Siegel RL, Jemal A. Lung cancer statistics. Adv Exp Med Biol. 2016;893:1–19. https://doi.org/10.1007/978-3-319-24223-1_1.

    Article  PubMed  Google Scholar 

  2. Forde PM, Ettinger DS. Targeted therapy for non-small-cell lung cancer: past, present and future. Expert Rev Anticancer Ther. 2013;13(6):745–58. https://doi.org/10.1586/era.13.47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947–57. https://doi.org/10.1056/NEJMoa0810699.

    Article  CAS  PubMed  Google Scholar 

  4. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353:123–32.

    Article  CAS  Google Scholar 

  5. Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13(3):239–46. https://doi.org/10.1016/S1470-2045(11)70393-X.

    Article  CAS  PubMed  Google Scholar 

  6. Goss G, Tsai CM, Shepherd FA, et al. Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2016;17(12):1643–52. https://doi.org/10.1016/S1470-2045(16)30508-3.

    Article  CAS  PubMed  Google Scholar 

  7. 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):113–25. https://doi.org/10.1056/NEJMoa1713137.

    Article  CAS  PubMed  Google Scholar 

  8. Curran WJ Jr, Paulus R, Langer CJ, et al. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011;103(19):1452–60. https://doi.org/10.1093/jnci/djr325.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2017;377(20):1919–29. https://doi.org/10.1056/NEJMoa1709937.

    Article  CAS  PubMed  Google Scholar 

  10. Shafrin J, Brookmeyer R, Peneva D, et al. The value of surrogate endpoints for predicting real-world survival across five cancer types. Curr Med Res Opin. 2016;32(4):731–9. https://doi.org/10.1185/03007995.2016.1140027.

    Article  PubMed  Google Scholar 

  11. Xing L, Wu G, Wang L, et al. A multicenter, randomized, open-label, phase II trial of erlotinib versus etoposide plus cisplatin with concurrent radiotherapy in unresectable stage III non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) activating mutation. J Clin Oncol. 2017;35(15_suppl):8531 Randomized clinical trial that directly compares and indicates higher efficacy of neoadjuvant EGFR TKI in EGFR-mutant stage III NSCLC.

    Article  Google Scholar 

  12. Lee Y, Han JY, Moon SH, et al. Incorporating erlotinib or irinotecan plus cisplatin into chemoradiotherapy for stage iii non-small cell lung cancer according to EGFR mutation status. Cancer Res Treat. 2017;49(4):981–9. https://doi.org/10.4143/crt.2016.522 Small sample size study comparing Erlotinib chemoradiation to radiation alone in stage III NSCLC.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kelly K, Chansky K, Gaspar LE, et al. Phase III trial of maintenance gefitinib or placebo after concurrent chemoradiotherapy and docetaxel consolidation in inoperable stage III non-small-cell lung cancer: SWOG S0023. J Clin Oncol. 2008;26(15):2450–6. https://doi.org/10.1200/JCO.2007.14.4824.

    Article  CAS  PubMed  Google Scholar 

  14. Ramella S, Alberti AM, Cammilluzzi E, et al. Erlotinib and concurrent chemoradiation in pretreated NSCLC patients: radiobiological basis and clinical results. Biomed Res Int. 2013;2013:403869. https://doi.org/10.1155/2013/403869.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Komaki R, Allen PK, Wei X, et al. Adding erlotinib to chemoradiation improves overall survival but not progression-free survival in stage III non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 2015;92(2):317–24. https://doi.org/10.1016/j.ijrobp.2015.02.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Casal J, Vasquez S, Leon L, et al. Erlotinib as maintenance therapy after concurrent chemoradiotherapy in patients (p) with stage III non-small cell lung cancer (NSCLC): a Galician lung cancer group phase II study. J Clin Oncol. 2009;27(15_suppl):7537.

    Google Scholar 

  17. Levy A, Bardet E, Lacas B, et al. A phase II open-label multicenter study of gefitinib in combination with irradiation followed by chemotherapy in patients with inoperable stage III non-small cell lung cancer. Oncotarget. 2017;8(9):15924–33. https://doi.org/10.18632/oncotarget.12741.

    Article  PubMed  Google Scholar 

  18. Griesinger F, Roeper J, Netchaeva M, et al. Intercalated EGFR TKI and chemotherapy induction therapy in EGFR mt+ NSCLC stage IIIA and IIIB: report of 5 cases. J Clin Oncol. 2016;34(15_suppl):e20059.

    Article  Google Scholar 

  19. Merlo V, Longo M, Novello S, Scagliotti GV. EGFR pathway in advanced non-small cell lung cancer. Front Biosci (Schol Ed). 2011;3:501–17.

    PubMed  Google Scholar 

  20. Fukuoka M, Wu YL, Thongprasert S, et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol. 2011;29(21):2866–74. https://doi.org/10.1200/JCO.2010.33.4235.

    Article  CAS  PubMed  Google Scholar 

  21. Lampaki S, Lazaridis G, Zarogoulidis K, et al. Defining the role of tyrosine kinase inhibitors in early stage non-small cell lung cancer. J Cancer. 2015;6(6):568–74. https://doi.org/10.7150/jca.11893.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kris MG, Natale RB, Herbst RS, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA. 2003;290(16):2149–58.

    Article  CAS  Google Scholar 

  23. Evans M, O’Sullivan B, Smith M, et al. Large-scale EGFR mutation testing in clinical practice: analysis of a series of 18,920 non-small cell lung cancer cases. Pathol Oncol Res. 2018. https://doi.org/10.1007/s12253-018-0460-2.

  24. Dillman RO, Seagren SL, Propert KJ, et al. A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer. N Engl J Med. 1990;323(14):940–5.

    Article  CAS  Google Scholar 

  25. Schaake-Koning C, van den Bogaert W, Dalesio O, et al. Effects of concomitant cisplatin and radiotherapy on inoperable non-small-cell lung cancer. N Engl J Med. 1992;326(8):524–30.

    Article  CAS  Google Scholar 

  26. Ang KK, Berkey BA, Tu X, et al. Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res. 2002;62(24):7350–6.

    CAS  PubMed  Google Scholar 

  27. Zhong W, Wu Y, Chen K, et al. CTONG 1103: Erlotinib versus gemcitabine plus cisplatin as neo-adjuvant treatment for stage IIIA-N2 EGFR-mutation non-small cell lung cancer (EMERGING): a randomised study. Ann Oncol 2018;29(8). doi: https://doi.org/10.1093/annonc/mdy424.058. Randomized trial comparing Erlotinib to standard of care chemotherapy in stage III NSCLC and indicates improved outcomes with Erlotinib.

  28. Yuan Y, Huang Q, Gu C, Chen H. Disease-free survival improved by use of adjuvant EGFR tyrosine kinase inhibitors in resectable non-small cell lung cancer: an updated meta-analysis. J Thorac Dis. 2017;9(12):5314–21. https://doi.org/10.21037/jtd.2017.12.58.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Lee CK, Man J, Lord S, et al. Clinical and molecular characteristics associated with survival among patients treated with checkpoint inhibitors for advanced non-small cell lung carcinoma: a systematic review and meta-analysis. JAMA Oncol. 2018;4(2):210–6. https://doi.org/10.1001/jamaoncol.2017.4427.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Division of Hematology and Oncology, MedStar Washington Hospital Center/Georgetown University, Washington, DC, USA

    Sanjal Desai, Chul Kim & Irina Veytsman

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  1. Sanjal Desai
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  2. Chul Kim
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Corresponding author

Correspondence to Irina Veytsman.

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Conflict of Interest

Sanjal Desai declares that she has no conflict of interest. Chul Kim received one-time travel support from Caris Life Sciences to an advisory board meeting in 2017; is the site PI for the CANOPY-1 trial (NCT03631199), funded by Novartis; and has received research support from AstraZeneca for an investigator-initiated trial of durvalumab in patients with viral infection and NSCLC. Irina Veytsman declares that she has no conflict of interest.

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Desai, S., Kim, C. & Veytsman, I. Role of Anti-EGFR Targeted Therapies in Stage III Locally Advanced Non-small Cell Lung Cancer: Give or Not to Give?. Curr Oncol Rep 21, 84 (2019). https://doi.org/10.1007/s11912-019-0835-x

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