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Review

Combining Anti-epidermal Growth Factor Receptor (EGFR) Therapy with Immunotherapy in Metastatic Colorectal Cancer (mCRC)

, , , , & ORCID Icon
Pages 185-192 | Received 17 Mar 2023, Accepted 30 Jun 2023, Published online: 13 Sep 2023

References

  • Kishore C, Bhadra P. Current advancements and future perspectives of immunotherapy in colorectal cancer research. Eur J Pharmacol. 2021;893:173819. doi: 10.1016/j.ejphar.2020.173819
  • Van Cutsem E, Oliveira J. Advanced colorectal cancer: eSMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2009;20(4):61–63. doi: 10.1093/annonc/mdp130
  • Florescu-Ţenea RM, Kamal AM, Mitruţ P, et al. Colorectal Cancer: an Update on Treatment Options and Future Perspectives. Curr Health Sci J. 2019;45(2):134–141. doi: 10.12865/CHSJ.45.02.02
  • Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351(4):337–345. doi: 10.1056/NEJMoa033025
  • Van Cutsem E, Köhne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360(14):1408–1417. doi: 10.1056/NEJMoa0805019
  • Douillard JY, Siena S, Cassidy J, et al. Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol. 2014;25(7):1346–1355. doi: 10.1093/annonc/mdu141
  • Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(10):1065–1075. doi: 10.1016/S1470-2045(14)70330-4
  • Fountzilas C, Bajor DL, Mukherjee S, et al. Phase Ib/II Study of Cetuximab plus Pembrolizumab in Patients with Advanced RAS Wild-Type Colorectal Cancer. Clin Cancer Res. 2021;27(24):6726–6736. doi: 10.1158/1078-0432.CCR-21-1650
  • Ott PA, Hodi FS, Kaufman HL, et al. Combination immunotherapy: a road map. J Immunother Cancer. 2017;5(1):16. doi: 10.1186/s40425-017-0218-5
  • Lazzari C, Karachaliou N, Bulotta A, et al. Combination of immunotherapy with chemotherapy and radiotherapy in lung cancer: is this the beginning of the end for cancer? Ther Adv Med Oncol. 2018;10:1758835918762094. doi: 10.1177/1758835918762094
  • Chowdhury PS, Chamoto K, Honjo T. Combination therapy strategies for improving PD-1 blockade efficacy: a new era in cancer immunotherapy. J Intern Med. 2018;283(2):110–120. doi: 10.1111/joim.12708
  • Overman MJ, Lonardi S, Wong KYM, et al. Durable Clinical Benefit with Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol. 2018;36(8):773–779. doi: 10.1200/JCO.2017.76.9901
  • Overman MJ, McDermott R, Leach JL, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017;18(9):1182–1191. doi: 10.1016/S1470-2045(17)30422-9
  • André T, Shiu KK, Kim TW, et al. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020;383(23):2207–2218. doi: 10.1056/NEJMoa2017699
  • Grothey A. Pembrolizumab in MSI-H-Dmmr Advanced Colorectal Cancer - a New Standard of Care. N Engl J Med. 2020;383(23):2283–2285. doi: 10.1056/NEJMe2031294
  • Barrueto L, Caminero F, Cash L, et al. Resistance to Checkpoint Inhibition in Cancer Immunotherapy. Transl Oncol. 2020;13(3):100738. doi: 10.1016/j.tranon.2019.12.010
  • Schmoll HJ, Arnold D, de Gramont A, et al. MODUL-a multicenter randomized clinical trial of biomarker-driven maintenance therapy following first-line standard induction treatment of metastatic colorectal cancer: an adaptable signal-seeking approach. J Cancer Res Clin Oncol. 2018;144(6):1197–1204. doi: 10.1007/s00432-018-2632-6
  • Coelho MA, de Carné Trécesson S, Rana S, et al. Oncogenic RAS Signaling Promotes Tumor Immunoresistance by Stabilizing PD-L1 mRNA. Immunity. 2017;47(6):1083–99.e6. doi: 10.1016/j.immuni.2017.11.016
  • Ganesh K, Stadler ZK, Cercek A, et al. Immunotherapy in colorectal cancer: rationale, challenges and potential. Nat Rev Gastroenterol Hepatol. 2019;16(6):361–375. doi: 10.1038/s41575-019-0126-x
  • Sotelo MJ, García-Paredes B, Aguado C, et al. Role of cetuximab in first-line treatment of metastatic colorectal cancer. World J Gastroenterol. 2014;20(15):4208–4219. doi: 10.3748/wjg.v20.i15.4208
  • Imai K, Takaoka A. Comparing antibody and small-molecule therapies for cancer. Nat Rev Cancer. 2006;6(9):714–727. doi: 10.1038/nrc1913
  • Chen S, Li X, Chen R, et al. Cetuximab intensifies the ADCC activity of adoptive NK cells in a nude mouse colorectal cancer xenograft model. Oncol Lett. 2016;12(3):1868–1876. doi: 10.3892/ol.2016.4835
  • Inoue Y, Hazama S, Suzuki N, et al. Cetuximab strongly enhances immune cell infiltration into liver metastatic sites in colorectal cancer. Cancer Sci. 2017;108(3):455–460. doi: 10.1111/cas.13162
  • den Eynde M V, Mlecnik B, Bindea G, et al. The Link between the Multiverse of Immune Microenvironments in Metastases and the Survival of Colorectal Cancer Patients. Cancer Cell. 2018;34(6):1012–26.e3. doi: 10.1016/j.ccell.2018.11.003
  • Schoppy DW, Sunwoo JB. Immunotherapy for Head and Neck Squamous Cell Carcinoma. Hematol Oncol Clin North Am. 2015;29(6):1033–1043. doi: 10.1016/j.hoc.2015.07.009
  • Lieberman J. The ABCs of granule-mediated cytotoxicity: new weapons in the arsenal. Nat Rev Immunol. 2003;3(5):361–370. doi: 10.1038/nri1083
  • Bhat R, Watzl C, Zimmer J. Serial killing of tumor cells by human natural killer cells–enhancement by therapeutic antibodies. PLoS One. 2007;2(3):e326. doi: 10.1371/journal.pone.0000326
  • Srivastava RM, Lee SC, Andrade Filho PA, et al. Cetuximab-activated natural killer and dendritic cells collaborate to trigger tumor antigen-specific T-cell immunity in head and neck cancer patients. Clin Cancer Res. 2013;19(7):1858–1872. doi: 10.1158/1078-0432.CCR-12-2426
  • Trivedi S, Srivastava RM, Concha-Benavente F, et al. Anti-EGFR Targeted Monoclonal Antibody Isotype Influences Antitumor Cellular Immunity in Head and Neck Cancer Patients. Clin Cancer Res. 2016;22(21):5229–5237. doi: 10.1158/1078-0432.CCR-15-2971
  • Lee SC, Srivastava RM, López-Albaitero A, et al. Natural killer (NK): dendritic cell (DC) cross talk induced by therapeutic monoclonal antibody triggers tumor antigen-specific T cell immunity. Immunol Res. 2011;50(2–3):248–254. doi: 10.1007/s12026-011-8231-0
  • Kubach J, Hubo M, Amendt C, et al. IgG1 anti-epidermal growth factor receptor antibodies induce CD8-dependent antitumor activity. Int J Cancer. 2015;136(4):821–830. doi: 10.1002/ijc.29037
  • Ferris RL, Lenz HJ, Trotta AM, et al. Rationale for combination of therapeutic antibodies targeting tumor cells and immune checkpoint receptors: harnessing innate and adaptive immunity through IgG1 isotype immune effector stimulation. Cancer Treat Rev. 2018;63:48–60.
  • Kroemer G, Galluzzi L, Kepp O, et al. Immunogenic cell death in cancer therapy. Annu Rev Immunol. 2013;31(1):51–72. doi: 10.1146/annurev-immunol-032712-100008
  • Pozzi C, Cuomo A, Spadoni I, et al. The EGFR-specific antibody cetuximab combined with chemotherapy triggers immunogenic cell death. Nat Med. 2016;22(6):624–631. doi: 10.1038/nm.4078
  • Jie HB, Gildener-Leapman N, Li J, et al. Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients. Br J Cancer. 2013;109(10):2629–2635. doi: 10.1038/bjc.2013.645
  • Jie HB, Schuler PJ, Lee SC, et al. CTLA-4+ Regulatory T Cells Increased in Cetuximab-Treated Head and Neck Cancer Patients Suppress NK Cell Cytotoxicity and Correlate with Poor Prognosis. Cancer Res. 2015;75(11):2200–2210. doi: 10.1158/0008-5472.CAN-14-2788
  • Ghiringhelli F, Ménard C, Terme M, et al. CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner. J Exp Med. 2005;202(8):1075–1085. doi: 10.1084/jem.20051511
  • Strauss L, Bergmann C, Szczepanski M, et al. A Unique Subset of CD4+CD25highFoxp3+ T Cells Secreting Interleukin-10 and Transforming Growth Factor-β1 Mediates Suppression in the Tumor Microenvironment. Clin Cancer Res. 2007;13(15):4345–4354. doi: 10.1158/1078-0432.CCR-07-0472
  • Woolston A, Khan K, Spain G, et al. Genomic and Transcriptomic Determinants of Therapy Resistance and Immune Landscape Evolution during Anti-EGFR Treatment in Colorectal Cancer. Cancer Cell. 2019;36(1):35–50 e9. doi: 10.1016/j.ccell.2019.05.013
  • Bellucci R, Martin A, Bommarito D, et al. Interferon-γ-induced activation of JAK1 and JAK2 suppresses tumor cell susceptibility to NK cells through upregulation of PD-L1 expression. Oncoimmunology. 2015;4(6):e1008824. doi: 10.1080/2162402X.2015.1008824
  • Concha-Benavente F, Srivastava RM, Trivedi S, et al. Identification of the Cell-Intrinsic and -Extrinsic Pathways Downstream of EGFR and IFNγ That Induce PD-L1 Expression in Head and Neck Cancer. Cancer Res. 2016;76(5):1031–1043. doi: 10.1158/0008-5472.CAN-15-2001
  • Akiyama Y, Nonomura C, Kondou R, et al. Immunological effects of the anti-programmed death-1 antibody on human peripheral blood mononuclear cells. Int J Oncol. 2016;49(3):1099–1107. doi: 10.3892/ijo.2016.3586
  • Qiao G, Yang L, Li Z, et al. Program death-1 regulates peripheral T cell tolerance via an anergy-independent mechanism. Clin Immunol. 2012;143(2):128–133. doi: 10.1016/j.clim.2012.02.006
  • Simpson TR, Li F, Montalvo-Ortiz W, et al. Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. J Exp Med. 2013;210(9):1695–1710. doi: 10.1084/jem.20130579
  • Tang Q, Boden EK, Henriksen KJ, et al. Distinct roles of CTLA-4 and TGF-beta in CD4+CD25+ regulatory T cell function. Eur J Immunol. 2004;34(11):2996–3005. doi: 10.1002/eji.200425143
  • JR G, AD L. CXCR3 ligands: redundant, collaborative and antagonistic functions. Immunol Cell Biol. 2011;89(2):207–215. doi: 10.1038/icb.2010.158
  • Holubec L, Polivka J Jr., Safanda M, et al. The Role of Cetuximab in the Induction of Anticancer Immune Response in Colorectal Cancer Treatment. Anticancer Res. 2016;36(9):4421–4426. doi: 10.21873/anticanres.10985
  • Boyerinas B, Jochems C, Fantini M, et al. Antibody-Dependent Cellular Cytotoxicity Activity of a Novel Anti-PD-L1 Antibody Avelumab (MSB0010718C) on Human Tumor Cells. Cancer Immunol Res. 2015;3(10):1148–1157. doi: 10.1158/2326-6066.CIR-15-0059
  • Fujii R, Friedman ER, Richards J, et al. Enhanced killing of chordoma cells by antibody-dependent cell-mediated cytotoxicity employing the novel anti-PD-L1 antibody avelumab. Oncotarget. 2016;7(23):33498–33511. doi: 10.18632/oncotarget.9256
  • Bourhis J, Stein A, Paul de Boer J, et al. Avelumab and cetuximab as a therapeutic combination: an overview of scientific rationale and current clinical trials in cancer. Cancer Treat Rev. 2021;97:102172. doi: 10.1016/j.ctrv.2021.102172
  • Veluchamy JP, Spanholtz J, Tordoir M, et al. Combination of NK Cells and Cetuximab to Enhance Anti-Tumor Responses in RAS Mutant Metastatic Colorectal Cancer. PLoS One. 2016;11(6):e0157830. doi: 10.1371/journal.pone.0157830
  • Fasano M, Della Corte CM, Di Liello R, et al. Induction of natural killer antibody-dependent cell cytotoxicity and of clinical activity of cetuximab plus avelumab in non-small cell lung cancer. ESMO Open. 2020;5(5):e000753. doi: 10.1136/esmoopen-2020-000753
  • Elbers JBW, Al-Mamgani A, Tesseslaar MET, et al. Immuno-radiotherapy with cetuximab and avelumab for advanced stage head and neck squamous cell carcinoma: results from a phase-I trial. Radiother Oncol. 2020;142:79–84. doi: 10.1016/j.radonc.2019.08.007
  • Lonardi S, Pietrantonio F, Prete AA, et al. 402MO Final results of the CARACAS study: randomized phase II trial of avelumab alone or with cetuximab for unresectable, locally advanced or metastatic squamous cell anal carcinoma progressed to at least one line of treatment. Ann Oncol. 2020;31:S412. doi: 10.1016/j.annonc.2020.08.513
  • Fasano M, Della Corte CM, Viscardi G, et al. Head and neck cancer: the role of anti-EGFR agents in the era of immunotherapy. Ther Adv Med Oncol. 2021;13:1758835920949418. doi: 10.1177/1758835920949418
  • Martinelli E, Martini G, Famiglietti V, et al. Cetuximab Rechallenge Plus Avelumab in Pretreated Patients with RAS Wild-type Metastatic Colorectal Cancer: the Phase 2 Single-Arm Clinical CAVE Trial. JAMA Oncol. 2021;7(10):1529–1535. doi: 10.1001/jamaoncol.2021.2915
  • Eynde MVD, Huyghe N, Cuyper AD, et al. Interim analysis of the AVETUXIRI Trial: avelumab combined with cetuximab and irinotecan for treatment of refractory microsatellite stable (MSS) metastatic colorectal cancer (Mcrc)—A proof of concept, open-label, nonrandomized phase IIa study. J Clin Oncol. 2021;39(3_suppl):80–. doi: 10.1200/JCO.2021.39.3_suppl.80
  • Stein A, Simnica D, Schultheiß C, et al. PD-L1 targeting and subclonal immune escape mediated by PD-L1 mutations in metastatic colorectal cancer. J Immunother Cancer. 2021;9(7):e002844. doi: 10.1136/jitc-2021-002844
  • Sebastian S, Heinemann, Volker V. FIRE-6 Studie. Forum. 2019;34(4):371–373. doi: 10.1007/s12312-019-0657-7
  • Martinelli E, Ciardiello D, Martini G, et al. Implementing anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer: challenges and future perspectives. Ann Oncol. 2020;31(1):30–40. doi: 10.1016/j.annonc.2019.10.007
  • Lee MS, Loehrer PJ, Imanirad I, et al. Phase II study of ipilimumab, nivolumab, and panitumumab in patients with KRAS/NRAS/BRAF wild-type (WT) microsatellite stable (MSS) metastatic colorectal cancer (mCRC). J Clin Oncol. 2021;39(3_suppl):7–. doi: 10.1200/JCO.2021.39.3_suppl.7
  • Meric-Bernstam F, Larkin J, Tabernero J, et al. Enhancing anti-tumour efficacy with immunotherapy combinations. Lancet. 2021;397(10278):1010–1022. doi: 10.1016/S0140-6736(20)32598-8
  • Guerrero RM, Labajos VA, Ballena SL, et al. Targeting BRAF V600E in metastatic colorectal cancer: where are we today? Ecancermedicalscience. 2022;16:1489. doi: 10.3332/ecancer.2022.1489
  • Ciardiello D, Vitiello PP, Cardone C, et al. Immunotherapy of colorectal cancer: challenges for therapeutic efficacy. Cancer Treat Rev. 2019;76:22–32. doi: 10.1016/j.ctrv.2019.04.003
  • Overman MJ, Ernstoff MS, Morse MA. Where We Stand with Immunotherapy in Colorectal Cancer: deficient Mismatch Repair, Proficient Mismatch Repair, and Toxicity Management. Am Soc Clin Oncol Educ Book. 2018;38(38):239–247. doi: 10.1200/EDBK_200821
  • Apetoh L, Ghiringhelli F, Tesniere A, et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med. 2007;13(9):1050–1059. doi: 10.1038/nm1622
  • Krysko DV, Garg AD, Kaczmarek A, et al. Immunogenic cell death and DAMPs in cancer therapy. Nat Rev Cancer. 2012;12(12):860–875. doi: 10.1038/nrc3380
  • Tran B, Kopetz S, Tie J, et al. Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer. Cancer. 2011;117(20):4623–4632. doi: 10.1002/cncr.26086
  • Corcoran RB, Atreya CE, Falchook GS, et al. Combined BRAF and MEK Inhibition with Dabrafenib and Trametinib in BRAF V600-Mutant Colorectal Cancer. J Clin Oncol. 2015;33(34):4023–4031. doi: 10.1200/JCO.2015.63.2471
  • Prahallad A, Sun C, Huang S, et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature. 2012;483(7387):100–103. doi: 10.1038/nature10868
  • Mao M, Tian F, Mariadason JM, et al. Resistance to BRAF inhibition in BRAF-mutant colon cancer can be overcome with PI3K inhibition or demethylating agents. Clin Cancer Res. 2013;19(3):657–667. doi: 10.1158/1078-0432.CCR-11-1446
  • Corcoran RB, André T, Atreya CE, et al. Combined BRAF, EGFR, and MEK Inhibition in Patients with BRAF(V600E)-Mutant Colorectal Cancer. Cancer Discov. 2018;8(4):428–443. doi: 10.1158/2159-8290.CD-17-1226
  • Hong DS, Morris VK, El Osta B, et al. Phase IB Study of Vemurafenib in Combination with Irinotecan and Cetuximab in Patients with Metastatic Colorectal Cancer with BRAFV600E Mutation. Cancer Discov. 2016;6(12):1352–1365. doi: 10.1158/2159-8290.CD-16-0050
  • Yaeger R, Cercek A, O’Reilly EM, et al. Pilot trial of combined BRAF and EGFR inhibition in BRAF-mutant metastatic colorectal cancer patients. Clin Cancer Res. 2015;21(6):1313–1320. doi: 10.1158/1078-0432.CCR-14-2779
  • Darvin P, Toor SM, Sasidharan Nair V, et al. Immune checkpoint inhibitors: recent progress and potential biomarkers. Exp Mol Med. 2018;50(12):1–11. doi: 10.1038/s12276-018-0191-1
  • Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27(8):1386–1422. doi: 10.1093/annonc/mdw235
  • Trivedi S, Concha-Benavente F, Srivastava RM, et al. Immune biomarkers of anti-EGFR monoclonal antibody therapy. Ann Oncol. 2015;26(1):40–47. doi: 10.1093/annonc/mdu156
  • García-Foncillas J, Sunakawa Y, Aderka D, et al. Distinguishing Features of Cetuximab and Panitumumab in Colorectal Cancer and Other Solid Tumors. Front Oncol. 2019;9:849. doi: 10.3389/fonc.2019.00849
  • Price TJ, Peeters M, Kim TW, et al. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol. 2014;15(6):569–579. doi: 10.1016/S1470-2045(14)70118-4

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