open access
Possibilities of applying a combination of targeted molecular therapies and immunotherapy in NSCLC patients
, 1, 1
Affiliations- Department of Pneumology, Oncology and Allergology, Medical University of Lublin, Lublin, Poland
open access
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.
Keywords
immunotherapy; lung cancer; targeted therapy; EGFR; ALK
About this articleTitle
Possibilities of applying a combination of targeted molecular therapies and immunotherapy in NSCLC patients
Journal
Nowotwory. Journal of Oncology
Issue
Article type
Review paper
Pages
184-189
Published online
2022-02-14
Page views
4796
Article views/downloads
373
DOI
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)- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018; 68(1): 7–30.
- 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.
- 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.
- 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.
- 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.
- Sharma P, Hu-Lieskovan S, Wargo JA, et al. Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell. 2017; 168(4): 707–723.
- 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).
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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).
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.