open access

Vol 72, No 3 (2022)
Review paper
Published online: 2022-02-14
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Possibilities of applying a combination of targeted molecular therapies and immunotherapy in NSCLC patients

Magdalena Wójcik-Superczyńska1, Tomasz Jankowski1, Paweł Krawczyk1
DOI: 10.5603/NJO.a2022.0012
·
Nowotwory. Journal of Oncology 2022;72(3):184-189.
Affiliations
  1. Department of Pneumology, Oncology and Allergology, Medical University of Lublin, Lublin, Poland

open access

Vol 72, No 3 (2022)
Review article
Published online: 2022-02-14

Abstract

Non-small cell lung cancer (NSCLC) advanced or metastatic with driver mutations (EGFR, ALK, ROS1) is treated with ty­rosine kinase inhibitors (TKIs), respectively anti-EGFR, anti-ALK or anti-ROS1. Immunotherapy with checkpoint inhibitors (anti-PD-1 or anti-PD-L1) alone or in combination with TKIs was considered as a treatment option in several studies, but results are not promising, furthermore the toxicity profile of such a combination is potentially unacceptable. The initial findings suggest that combination therapy has failed to demonstrate clinically meaningful efficacy and there are no strong signals of its future development.

Abstract

Non-small cell lung cancer (NSCLC) advanced or metastatic with driver mutations (EGFR, ALK, ROS1) is treated with ty­rosine kinase inhibitors (TKIs), respectively anti-EGFR, anti-ALK or anti-ROS1. Immunotherapy with checkpoint inhibitors (anti-PD-1 or anti-PD-L1) alone or in combination with TKIs was considered as a treatment option in several studies, but results are not promising, furthermore the toxicity profile of such a combination is potentially unacceptable. The initial findings suggest that combination therapy has failed to demonstrate clinically meaningful efficacy and there are no strong signals of its future development.

Get Citation

Keywords

immunotherapy; lung cancer; targeted therapy; EGFR; ALK

About this article
Title

Possibilities of applying a combination of targeted molecular therapies and immunotherapy in NSCLC patients

Journal

Nowotwory. Journal of Oncology

Issue

Vol 72, No 3 (2022)

Article type

Review paper

Pages

184-189

Published online

2022-02-14

Page views

121

Article views/downloads

52

DOI

10.5603/NJO.a2022.0012

Bibliographic record

Nowotwory. Journal of Oncology 2022;72(3):184-189.

Keywords

immunotherapy
lung cancer
targeted therapy
EGFR
ALK

Authors

Magdalena Wójcik-Superczyńska
Tomasz Jankowski
Paweł Krawczyk

References (32)
  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018; 68(1): 7–30.
  2. Wojas-Krawczyk K, Krawczyk P. Anti-PD-1 and anti-PD-L1 antibodies in combination with other methods of treatment – is it the future of therapy for advanced NSCL? Immunotherapy. 2019; 1: 6–15.
  3. Karachaliou N, Gonzalez-Cao M, Sosa A, et al. The combination of checkpoint immunotherapy and targeted therapy in cancer. Ann Transl Med. 2017; 5(19): 388.
  4. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015; 373(17): 1627–1639.
  5. Herbst R, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016; 387(10027): 1540–1550.
  6. Sharma P, Hu-Lieskovan S, Wargo JA, et al. Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell. 2017; 168(4): 707–723.
  7. Ferrara MG, Di Noia V, D'Argento E, et al. Oncogene-Addicted Non-Small-Cell Lung Cancer: Treatment Opportunities and Future Perspectives. Cancers (Basel). 2020; 12(5).
  8. Cheng Y, Mok TS, Zhou X, et al. The epidermal growth factor receptor intron1 (CA) n microsatellite polymorphism is a potential predictor of treatment outcome in patients with advanced lung cancer treated with Gefitinib. Eur J Pharmacol. 2007; 570(1-3): 175–181.
  9. Marchetti A, Martella C, Felicioni L, et al. EGFR mutations in non-small-cell lung cancer: analysis of a large series of cases and development of a rapid and sensitive method for diagnostic screening with potential implications on pharmacologic treatment. J Clin Oncol. 2005; 23(4): 857–865.
  10. Remon J, Caramella C, Jovelet C, et al. Osimertinib benefit in EGFR-mutant NSCLC patients with T790M-mutation detected by circulating tumour DNA. Ann Oncol. 2017; 28(4): 784–790.
  11. Zhu C, Zhuang W, Chen L, et al. Frontiers of ctDNA, targeted therapies, and immunotherapy in non-small-cell lung cancer. Transl Lung Cancer Res. 2020; 9(1): 111–138.
  12. Kim H, Kim SH, Kim MJ, et al. EGFR inhibitors enhanced the susceptibility to NK cell-mediated lysis of lung cancer cells. J Immunother. 2011; 34(4): 372–381.
  13. Sheng J, Fang W, Liu X, et al. Impact of gefitinib in early stage treatment on circulating cytokines and lymphocytes for patients with advanced non-small cell lung cancer. Onco Targets Ther. 2017; 10: 1101–1110.
  14. Iwai Y, Ishida M, Tanaka Y, et al. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A. 2002; 99(19): 12293–12297.
  15. Ota K, Azuma K, Kawahara A, et al. Induction of PD-L1 Expression by the EML4-ALK Oncoprotein and Downstream Signaling Pathways in Non-Small Cell Lung Cancer. Clin Cancer Res. 2015; 21(17): 4014–4021.
  16. Azuma K, Ota K, Kawahara A, et al. Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall-cell lung cancer. Ann Oncol. 2014; 25(10): 1935–1940.
  17. Chen N, Fang W, Zhan J, et al. Upregulation of PD-L1 by EGFR Activation Mediates the Immune Escape in EGFR-Driven NSCLC: Implication for Optional Immune Targeted Therapy for NSCLC Patients with EGFR Mutation. J Thorac Oncol. 2015; 10(6): 910–923.
  18. Karachaliou N, Gonzalez-Cao M, Sosa A, et al. The combination of checkpoint immunotherapy and targeted therapy in cancer. Ann Transl Med. 2017; 5(19): 388.
  19. Lee CK, Man J, Lord S, et al. Checkpoint Inhibitors in Metastatic EGFR-Mutated Non-Small Cell Lung Cancer-A Meta-Analysis. J Thorac Oncol. 2017; 12(2): 403–407.
  20. Rittmeyer A, Barlesi F, Waterkamp D, et al. OAK Study Group. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017; 389(10066): 255–265.
  21. Gainor JF, Shaw AT, Sequist LV, et al. EGFR Mutations and ALK Rearrangements Are Associated with Low Response Rates to PD-1 Pathway Blockade in Non-Small Cell Lung Cancer: A Retrospective Analysis. Clin Cancer Res. 2016; 22(18): 4585–4593.
  22. Yang JCH, Gadgeel SM, Sequist LV, et al. Pembrolizumab in Combination With Erlotinib or Gefitinib as First-Line Therapy for Advanced NSCLC With Sensitizing EGFR Mutation. J Thorac Oncol. 2019; 14(3): 553–559.
  23. Karachaliou N, Gonzalez-Cao M, Sosa A, et al. The combination of checkpoint immunotherapy and targeted therapy in cancer. Ann Transl Med. 2017; 5(19): 388.
  24. Yang JCH, Shepherd FA, Kim DW, et al. Osimertinib Plus Durvalumab versus Osimertinib Monotherapy in EGFR T790M-Positive NSCLC following Previous EGFR TKI Therapy: CAURAL Brief Report. J Thorac Oncol. 2019; 14(5): 933–939.
  25. Ma B, Rudin CM, Cervantes A, et al. 441O Preliminary safety and clinical activity of erlotinib plus atezolizumab from a Phase Ib study in advanced NSCLC. Ann Oncol. 2016; 27(suppl_9).
  26. Gibbons DL, Chow LQ, Kim DW, et al. 57O Efficacy, safety and tolerability of MEDI4736 (durvalumab [D]), a human IgG1 anti-programmed cell death-ligand-1 (PD-L1) antibody, combined with gefitinib (G): A phase I expansion in TKI-naïve patients (pts) with EGFR mutant NSCLC. J Thorac Oncol. 2016; 11(4): S79.
  27. Antonia S, Goldberg SB, Balmanoukian A, et al. Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. Lancet Oncol. 2016; 17(3): 299–308.
  28. Spigel DR, Reynolds C, Waterhouse D, et al. Phase 1/2 Study of the Safety and Tolerability of Nivolumab Plus Crizotinib for the First-Line Treatment of Anaplastic Lymphoma Kinase Translocation - Positive Advanced Non-Small Cell Lung Cancer (CheckMate 370). J Thorac Oncol. 2018; 13(5): 682–688.
  29. Gettinger S, Chow LQ, Borghaei H, et al. Safety and response with nivolumab (anti-PD-1; BMS-936558, ONO-4538) plus erlotinib in patients (pts) with epidermal growth factor receptor mutant (EGFR MT) advanced NSCLC. Int J Radiat Oncol Biol Phys. 2014; 90: S34–5.
  30. Moya-Horno I, Viteri S, Karachaliou N, et al. Combination of immunotherapy with targeted therapies in advanced non-small cell lung cancer (NSCLC). Ther Adv Med Oncol. 2018; 10: 1758834017745012.
  31. Bruno D, Dowlati A. Immunotherapy in EGFR mutant non-small cell lung cancer: when, who and how? Transl Lung Cancer Res. 2019; 8(5): 710–714.
  32. ESMO Oncology News. Combination immunotherapies for immune hot, altered and cold tumor. Understanding underlining mechanisms is crucial to boost a weak antitumour immunity. Date: 29 May 2019. Topics: Cancer Immunology and Immunotherapy.

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