Immune checkpoint inhibitors in metastatic colorectal cancer therapy (a review)
DOI:
https://doi.org/10.14739/2310-1210.2022.3.246760Keywords:
colorectal cancer, metastasis, immune checkpoint inhibitors, radiotherapy, chemotherapy, drug targetingAbstract
Aim – to characterize the clinical achievements of therapy with immune checkpoint inhibitors in patients with metastatic colorectal cancer and to analyze the trial results of combined use of these inhibitors with chemotherapy, radiotherapy, and targeted drugs.
Results. The review has summarized the clinical trial results of immune checkpoint inhibitors (ICI) in patients with MSI-H/dMMR metastatic colorectal cancer (mCRC), which were the basis for FDA approval of these drugs use. The results of the ICI combined use in patients with MSS/pMMR status have been described. Potential biomarkers of response to ICI in patients with CRC have been characterized.
Conclusions. The effectiveness of ICI and their combinations has been proven in patients with MSI-H/dMMR status. Trials using combination strategies in MSS mCRC patients are ongoing and limited to small phase I/II trials and do not always have a comparison group. There is no evidence of a durable response rate to treatment when combination strategies are used.
References
Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71(3), 209-249. https://doi.org/10.3322/caac.21660
Emambux, S., Tachon, G., Junca, A., & Tougeron, D. (2018). Results and challenges of immune checkpoint inhibitors in colorectal cancer. Expert Opinion on Biological Therapy, 18(5), 561-573. https://doi.org/10.1080/14712598.2018.1445222
Hirano, H., Takashima, A., Hamaguchi, T., Shida, D., Kanemitsu, Y., & Colorectal Cancer Study Group (CCSG) of the Japan Clinical Oncology Group (JCOG). (2021). Current status and perspectives of immune checkpoint inhibitors for colorectal cancer. Japanese Journal of Clinical Oncology, 51(1), 10-19. https://doi.org/10.1093/jjco/hyaa200
Salem, M. E., Bodor, J. N., Puccini, A., Xiu, J., Goldberg, R. M., Grothey, A., Korn, W. M., Shields, A. F., Worrilow, W. M., Kim, E. S., Lenz, H. J., Marshall, J. L., & Hall, M. J. (2020). Relationship between MLH1, PMS2, MSH2 and MSH6 gene-specific alterations and tumor mutational burden in 1057 microsatellite instability-high solid tumors. International Journal of Cancer, 147(10), 2948-2956. https://doi.org/10.1002/ijc.33115
Lenz, H.-J., Lonardi, S., Zagonel, V., Van Cutsem, E., Limon, M. L., Wong, M., Hendlisz, A., Aglietta, M., Garcia-Alfonso, P., Neyns, B., Gelsomino, F., Cardin, D. B., Dragovich, T., Shah, U., Yang, J., Ledeine, J.-M., & Overman, M. J. (2020). Nivolumab (NIVO) + low-dose ipilimumab (IPI) as first-line (1L) therapy in microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Two-year clinical update. Journal of Clinical Oncology, 38(15_suppl), 4040. https://doi.org/10.1200/jco.2020.38.15_suppl.4040
Shiu, K.-K., Andre, T., Kim, T. W., Jensen, B. V., Jensen, L. H., Punt, C. J. A., Smith, D. M., Garcia-Carbonero, R., Benavides, M., Gibbs, P., De La Fouchardiere, C., Rivera, F., Elez, E., Bendell, J. C., Le, D. T., Yoshino, T., Yang, P., Farooqui, M. Z. H., Marinello, P., & Diaz, L. A. (2021). KEYNOTE-177: Phase III randomized study of pembrolizumab versus chemotherapy for microsatellite instability-high advanced colorectal cancer. Journal of Clinical Oncology, 39(3_suppl), 6. https://doi.org/10.1200/jco.2021.39.3_suppl.6
Le, D. T., Durham, J. N., Smith, K. N., Wang, H., Bartlett, B. R., Aulakh, L. K., Lu, S., Kemberling, H., Wilt, C., Luber, B. S., Wong, F., Azad, N. S., Rucki, A. A., Laheru, D., Donehower, R., Zaheer, A., Fisher, G. A., Crocenzi, T. S., Lee, J. J., Greten, T. F., … Diaz, L. A., Jr. (2017). Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science, 357(6349), 409-413. https://doi.org/10.1126/science.aan6733
Le, D. T., Kim, T. W., Van Cutsem, E., Geva, R., Jäger, D., Hara, H., Burge, M., O'Neil, B., Kavan, P., Yoshino, T., Guimbaud, R., Taniguchi, H., Elez, E., Al-Batran, S. E., Boland, P. M., Crocenzi, T., Atreya, C. E., Cui, Y., Dai, T., Marinello, P., … André, T. (2020). Phase II Open-Label Study of Pembrolizumab in Treatment-Refractory, Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: KEYNOTE-164. Journal of Clinical Oncology, 38(1), 11-19. https://doi.org/10.1200/JCO.19.02107
Marabelle, A., Le, D. T., Ascierto, P. A., Di Giacomo, A. M., De Jesus-Acosta, A., Delord, J. P., Geva, R., Gottfried, M., Penel, N., Hansen, A. R., Piha-Paul, S. A., Doi, T., Gao, B., Chung, H. C., Lopez-Martin, J., Bang, Y. J., Frommer, R. S., Shah, M., Ghori, R., Joe, A. K., … Diaz, L. A., Jr. (2020). Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. Journal of Clinical Oncology, 38(1), 1-10. https://doi.org/10.1200/JCO.19.02105
Overman, M. J., McDermott, R., Leach, J. L., Lonardi, S., Lenz, H. J., Morse, M. A., Desai, J., Hill, A., Axelson, M., Moss, R. A., Goldberg, M. V., Cao, Z. A., Ledeine, J. M., Maglinte, G. A., Kopetz, S., & André, T. (2017). Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. The Lancet Oncology, 18(9), 1182-1191. https://doi.org/10.1016/S1470-2045(17)30422-9
Overman, M. J., Lonardi, S., Wong, K., Lenz, H. J., Gelsomino, F., Aglietta, M., Morse, M. A., Van Cutsem, E., McDermott, R., Hill, A., Sawyer, M. B., Hendlisz, A., Neyns, B., Svrcek, M., Moss, R. A., Ledeine, J. M., Cao, Z. A., Kamble, S., Kopetz, S., & André, T. (2018). Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. Journal of Clinical Oncology, 36(8), 773-779. https://doi.org/10.1200/JCO.2017.76.9901
Emens, L. A., & Middleton, G. (2015). The Interplay of Immunotherapy and Chemotherapy: Harnessing Potential Synergies. Cancer Immunology Research, 3(5), 436-443. https://doi.org/10.1158/2326-6066.CIR-15-0064
Vincent, J., Mignot, G., Chalmin, F., Ladoire, S., Bruchard, M., Chevriaux, A., Martin, F., Apetoh, L., Rébé, C., & Ghiringhelli, F. (2010). 5-Fluorouracil Selectively Kills Tumor-Associated Myeloid-Derived Suppressor Cells Resulting in Enhanced T Cell-Dependent Antitumor Immunity. Cancer Research, 70(8), 3052-3061. https://doi.org/10.1158/0008-5472.CAN-09-3690
Sun, F., Cui, L., Li, T., Chen, S., Song, J., & Li, D. (2019). Oxaliplatin induces immunogenic cells death and enhances therapeutic efficacy of checkpoint inhibitor in a model of murine lung carcinoma. Journal of Receptors and Signal Transduction, 39(3), 208-214. https://doi.org/10.1080/10799893.2019.1655050
Tesniere, A., Schlemmer, F., Boige, V., Kepp, O., Martins, I., Ghiringhelli, F., Aymeric, L., Michaud, M., Apetoh, L., Barault, L., Mendiboure, J., Pignon, J. P., Jooste, V., van Endert, P., Ducreux, M., Zitvogel, L., Piard, F., & Kroemer, G. (2010). Immunogenic death of colon cancer cells treated with oxaliplatin. Oncogene, 29(4), 482-491. https://doi.org/10.1038/onc.2009.356
Yamamura, Y., Tsuchikawa, T., Miyauchi, K., Takeuchi, S., Wada, M., Kuwatani, T., Kyogoku, N., Kuroda, A., Maki, T., Shichinohe, T., & Hirano, S. (2015). The key role of calreticulin in immunomodulation induced by chemotherapeutic agents. International Journal of Clinical Oncology, 20(2), 386-394. https://doi.org/10.1007/s10147-014-0719-x
Maeda, K., Hazama, S., Tokuno, K., Kan, S., Maeda, Y., Watanabe, Y., Kamei, R., Shindo, Y., Maeda, N., Yoshimura, K., Yoshino, S., & Oka, M. (2011). Impact of Chemotherapy for Colorectal Cancer on Regulatory T-Cells and Tumor Immunity. Anticancer Research, 31(12), 4569-4574.
Shahda, S., Noonan, A. M., Bekaii-Saab, T. S., O’Neil, B. H., Sehdev, A., Shaib, W. L., Helft, P. R., Loehrer, P. J., Tong, Y., Liu, Z., & El-Rayes, B. F. (2017). A phase II study of pembrolizumab in combination with mFOLFOX6 for patients with advanced colorectal cancer. Journal of Clinical Oncology, 35(15_suppl), 3541. https://doi.org/10.1200/jco.2017.35.15_suppl.3541
Ghiringhelli, F., Chibaudel, B., Taieb, J., Bennouna, J., Martin-Babau, J., Fonck, M., Borg, C., Cohen, R., Thibaudin, M., Limagne, E., & Fumet, J.-D. (2020). Durvalumab and tremelimumab in combination with FOLFOX in patients with RAS-mutated, microsatellite-stable, previously untreated metastatic colorectal cancer (MCRC): Results of the first intermediate analysis of the phase Ib/II MEDETREME trial. Journal of Clinical Oncology, 38(15_suppl), 3006. https://doi.org/10.1200/jco.2020.38.15_suppl.3006
Kim, R., Chaves, J., Kavan, P., Fakih, M., Kortmansky, J. S., Spencer, K., Wong, L., Tehfe, M., Li, J. J., Eyring, A. D., Mayo, C., & Chiorean, E. G. (2020). 493P Pembrolizumab (pembro) plus mFOLFOX7 or FOLFIRI in patients (pts) with metastatic colorectal cancer (mCRC): Updated results from KEYNOTE-651 cohorts B and D. Annals of Oncology, 31(Suppl. 4), S450. https://doi.org/10.1016/j.annonc.2020.08.604
Tang, C., Wang, X., Soh, H., Seyedin, S., Cortez, M. A., Krishnan, S., Massarelli, E., Hong, D., Naing, A., Diab, A., Gomez, D., Ye, H., Heymach, J., Komaki, R., Allison, J. P., Sharma, P., & Welsh, J. W. (2014). Combining Radiation and Immunotherapy: A New Systemic Therapy for Solid Tumors? Cancer Immunology Research, 2(9), 831-838. https://doi.org/10.1158/2326-6066.CIR-14-0069
Derer, A., Frey, B., Fietkau, R., & Gaipl, U. S. (2016). Immune-modulating properties of ionizing radiation: rationale for the treatment of cancer by combination radiotherapy and immune checkpoint inhibitors. Cancer Immunology, Immunotherapy, 65(7), 779-786. https://doi.org/10.1007/s00262-015-1771-8
Rückert, M., Flohr, A. S., Hecht, M., & Gaipl, U. S. (2021). Radiotherapy and the immune system: More than just immune suppression. Stem Cells, 39(9), 1155-1165. https://doi.org/10.1002/stem.3391
Parikh, A. R., Clark, J. W., Wo, J. Y.-L., Yeap, B. Y., Allen, J. N., Blaszkowsky, L S., Ryan, D. P., Giantonio, B. J., Weekes, C. D., Zhu, A. X., Van Seventer, E. E., Matlack, L., Foreman, B., Ly, L., Drapek, L. C., Ting, D. T., Corcoran, R. B., & Hong, T. S. (2019). A phase II study of ipilimumab and nivolumab with radiation in microsatellite stable (MSS) metastatic colorectal adenocarcinoma (mCRC). Journal of Clinical Oncology, 37(15_suppl), 3514. https://doi.org/10.1200/jco.2019.37.15_suppl.3514
Segal, N. H., Cercek, A., Ku, G., Wu, A. J., Rimner, A., Khalil, D. N., Reidy-Lagunes, D., Cuaron, J., Yang, T. J., Weiser, M. R., Romesser, P. B., Stadler, Z. K., Varghese, A. M., Ganesh, K., Yaeger, R., Connell, L. C., Faleck, D., Abou-Alfa, G. K., Mcauliffe, K. C., Vaiskauskas, P., … Saltz, L. B. (2021). Phase II Single-arm Study of Durvalumab and Tremelimumab with Concurrent Radiotherapy in Patients with Mismatch Repair-proficient Metastatic Colorectal Cancer. Clinical Cancer Research, 27(8), 2200-2208. https://doi.org/10.1158/1078-0432.CCR-20-2474
Yang, J., Bi, F., & Gou, H. (2021). Complete Pathologic Response After Concurrent Treatment with Pembrolizumab and Radiotherapy in Metastatic Colorectal Cancer: A Case Report. OncoTargets and Therapy, 14, 2555-2561. https://doi.org/10.2147/OTT.S298333
Van Cutsem, E., Cervantes, A., Adam, R., Sobrero, A., Van Krieken, J. H., Aderka, D., Aranda Aguilar, E., Bardelli, A., Benson, A., Bodoky, G., Ciardiello, F., D'Hoore, A., Diaz-Rubio, E., Douillard, J. Y., Ducreux, M., Falcone, A., Grothey, A., Gruenberger, T., Haustermans, K., Heinemann, V., … Arnold, D. (2016). ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Annals of Oncology, 27(8), 1386-1422. https://doi.org/10.1093/annonc/mdw235
Ferris, R. L., Lenz, H.-J., Trotta, A. M., García-Foncillas, J., Schulten, J., Audhuy, F., Merlano, M., & Milano, G. (2018). 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 Treatment Reviews, 63, 48-60. https://doi.org/10.1016/j.ctrv.2017.11.008
Veluchamy, J. P., Spanholtz, J., Tordoir, M., Thijssen, V. L., Heideman, D. A., Verheul, H. M., de Gruijl, T. D., & van der Vliet, H. J. (2016). Combination of NK Cells and Cetuximab to Enhance Anti-Tumor Responses in RAS Mutant Metastatic Colorectal Cancer. PLOS ONE, 11(6), Article e0157830. https://doi.org/10.1371/journal.pone.0157830
Inoue, Y., Hazama, S., Suzuki, N., Tokumitsu, Y., Kanekiyo, S., Tomochika, S., Tsunedomi, R., Tokuhisa, Y., Iida, M., Sakamoto, K., Takeda, S., Ueno, T., Yoshino, S., & Nagano, H. (2017). Cetuximab strongly enhances immune cell infiltration into liver metastatic sites in colorectal cancer. Cancer Science, 108(3), 455-460. https://doi.org/10.1111/cas.13162
Stein, A., Binder, M., Bokemeyer, C., Al Batran, S. E., Hinke, A., & Hegewisch-Becker, S. (2017). Avelumab and cetuximab in combination with FOLFOX in patients with previously untreated metastatic colorectal cancer (MCRC): The phase II AVETUX-CRC trial (AIO KRK 0216). Journal of Clinical Oncology, 35(15_suppl), TPS3620. https://doi.org/10.1200/jco.2017.35.15_suppl.tps3620
Stintzing, S., & Heinemann, V. (2019). FIRE-6 Studie. Forum, 34(4), 371-373. https://doi.org/10.1007/s12312-019-0657-7
Fountzilas, C., Mukherjee, S., Saltzman, J., Bajor, D., Muhitch, J., Abrams, S., Maguire, O., Minderman, H., Wang, K., Hutson, A., Hicks, K., Ventola, J., Kalinski, P., Iyer, R., & Boland, P. (2020). P-156 A phase Ib/II study of cetuximab and pembrolizumab in metastatic colorectal cancer. Annals of Oncology, 31(Suppl. 3), S140. https://doi.org/10.1016/j.annonc.2020.04.238
Van Den Eynde, M., Huyghe, N., De Cuyper, A., Sinapi, I., Ferrier, M., Gilet, M., Van Maanen, A., Castella, M.-L., Galon, J., & Carrasco, J. (2021). 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. Journal of Clinical Oncology, 39(3_suppl), 80. https://doi.org/10.1200/jco.2021.39.3_suppl.80
Martini, G., Napolitano, S., Famiglietti, V., De Braud, F. G., Terminiello, M., Borrelli, C., Vitiello, P. P., Avallone, A., Normanno, N., Maiello, E., Falcone, A., Santabarbara, G., Pinto, C., Santini, D., Di Liello, A., Renato, D., Esposito, L., Marrone, F., Troiani, T., & Ciardiello, D. (2021). Final results from the CAVE (cetuximab rechallenge plus avelumab) mCRC phase II trial: Skin toxicity as a predictor of clinical activity. Journal of Clinical Oncology, 39(15_suppl), 3578. https://doi.org/10.1200/jco.2021.39.15_suppl.3578
Fukumura, D., Kloepper, J., Amoozgar, Z., Duda, D. G., & Jain, R. K. (2018). Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges. Nature Reviews Clinical Oncology, 15(5), 325-340. https://doi.org/10.1038/nrclinonc.2018.29
Hack, S. P., Zhu, A. X., & Wang, Y. (2020). Augmenting Anticancer Immunity Through Combined Targeting of Angiogenic and PD-1/PD-L1 Pathways: Challenges and Opportunities. Frontiers in Immunology, 11, Article 598877. https://doi.org/10.3389/fimmu.2020.598877
Voron, T., Colussi, O., Marcheteau, E., Pernot, S., Nizard, M., Pointet, A. L., Latreche, S., Bergaya, S., Benhamouda, N., Tanchot, C., Stockmann, C., Combe, P., Berger, A., Zinzindohoue, F., Yagita, H., Tartour, E., Taieb, J., & Terme, M. (2015). VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors. Journal of Experimental Medicine, 212(2), 139-148. https://doi.org/10.1084/jem.20140559
Mettu, N. B., Twohy, E., Ou, F.-S., Halfdanarson, T. R., Lenz, H. J., Breakstone, R., Boland, P. M., Crysler, O., Wu, C., Grothey, A., Nixon, A. B., Bolch, E., Niedzwiecki, D., Fruth, B., Schweitzer, B., Elsing, A., Hurwitz, H., Fakih, M. G., & Bekaii-Saab, T. (2019). 533PD - BACCI: A phase II randomized, double-blind, multicenter, placebo-controlled study of capecitabine (C) bevacizumab (B) plus atezolizumab (A) or placebo (P) in refractory metastatic colorectal cancer (mCRC): An ACCRU network study. Annals of Oncology, 30(Suppl. 5), v203. https://doi.org/10.1093/annonc/mdz246.011
Grothey, A., Tabernero, J., Arnold, D., De Gramont, A., Ducreux, M. P., O’Dwyer, P. J., Van Cutsem, E., Bosanac, I., Srock, S., Mancao, C., Gilberg, F., Winter, J., & Schmoll, H.-J. (2018). LBA19 - Fluoropyrimidine (FP) + bevacizumab (BEV) + atezolizumab vs FP/BEV in BRAFwt metastatic colorectal cancer (mCRC): Findings from Cohort 2 of MODUL - a multicentre, randomized trial of biomarker-driven maintenance treatment following first-line induction therapy. Annals of Oncology, 29(Suppl. 8), viii714-viii715. https://doi.org/10.1093/annonc/mdy424.020
Antoniotti, C., Borelli, B., Rossini, D., Pietrantonio, F., Morano, F., Salvatore, L., Lonardi, S., Marmorino, F., Tamberi, S., Corallo, S., Tortora, G., Bergamo, F., Brunella, D. S., Boccaccino, A., Grassi, E., Racca, P., Tamburini, E., Aprile, G., Moretto, R., Boni, L., … Cremolini, C. (2020). AtezoTRIBE: a randomised phase II study of FOLFOXIRI plus bevacizumab alone or in combination with atezolizumab as initial therapy for patients with unresectable metastatic colorectal cancer. BMC Cancer, 20(1), Article 683. https://doi.org/10.1186/s12885-020-07169-6
Hara, H., Fukuoka, S., Takahashi, N., Kojima, T., Kawazoe, A., Asayama, M., Yoshii, T., Kotani, D., Tamura, H., Mikamoto, Y., Sugama, A., Wakabayashi, M., Nomura, S., Sato, A., Togashi, Y., Nishikawa, H., & Shitara, K. (2019). SO-007 - Regorafenib plus nivolumab in patients with advanced colorectal or gastric cancer: an open-label, dose-finding, and dose-expansion phase 1b trial (REGONIVO, EPOC1603). Annals of Oncology, 30(Suppl. 4), iv124. https://doi.org/10.1093/annonc/mdz157.006
Cousin, S., Cantarel, C., Guegan, J. P., Gomez-Roca, C., Metges, J. P., Adenis, A., Pernot, S., Bellera, C., Kind, M., Auzanneau, C., Le Loarer, F., Soubeyran, I., Bessede, A., & Italiano, A. (2021). Regorafenib-Avelumab Combination in Patients with Microsatellite Stable Colorectal Cancer (REGOMUNE): A Single-arm, Open-label, Phase II Trial. Clinical Cancer Research, 27(8), 2139-2147. https://doi.org/10.1158/1078-0432.CCR-20-3416
Liu, J., Huang, X., Liu, H., Wei, C., Ru, H., Qin, H., Lai, H., Meng, Y., Wu, G., Xie, W., Mo, X., Johnson, C. H., Zhang, Y., & Tang, W. (2021). Immune landscape and prognostic immune-related genes in KRAS-mutant colorectal cancer patients. Journal of Translational Medicine, 19(1), Article 27. https://doi.org/10.1186/s12967-020-02638-9
Petanidis, S., Anestakis, D., Argyraki, M., Hadzopoulou-Cladaras, M., & Salifoglou, A. (2013). Differential Expression of IL-17, 22 and 23 in the Progression of Colorectal Cancer in Patients with K-ras Mutation: Ras Signal Inhibition and Crosstalk with GM-CSF and IFN-γ. PLOS ONE, 8(9), Article e73616. https://doi.org/10.1371/journal.pone.0073616
Liao, W., Overman, M. J., Boutin, A. T., Shang, X., Zhao, D., Dey, P., Li, J., Wang, G., Lan, Z., Li, J., Tang, M., Jiang, S., Ma, X., Chen, P., Katkhuda, R., Korphaisarn, K., Chakravarti, D., Chang, A., Spring, D. J., Chang, Q., … DePinho, R. A. (2019). KRAS-IRF2 Axis Drives Immune Suppression and Immune Therapy Resistance in Colorectal Cancer. Cancer Cell, 35(4), 559-572.e7. https://doi.org/10.1016/j.ccell.2019.02.008
Canon, J., Rex, K., Saiki, A. Y., Mohr, C., Cooke, K., Bagal, D., Gaida, K., Holt, T., Knutson, C. G., Koppada, N., Lanman, B. A., Werner, J., Rapaport, A. S., San Miguel, T., Ortiz, R., Osgood, T., Sun, J. R., Zhu, X., McCarter, J. D., Volak, L. P., … Lipford, J. R. (2019). The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature, 575(7781), 217-223. https://doi.org/10.1038/s41586-019-1694-1
Galluzzi, L. (2020). Targeting Mutant KRAS for Immunogenic Cell Death Induction. Trends in Pharmacological Sciences, 41(1), 1-3. https://doi.org/10.1016/j.tips.2019.11.004
Ebert, P., Cheung, J., Yang, Y., McNamara, E., Hong, R., Moskalenko, M., Gould, S. E., Maecker, H., Irving, B. A., Kim, J. M., Belvin, M., & Mellman, I. (2016). MAP Kinase Inhibition Promotes T Cell and Anti-tumor Activity in Combination with PD-L1 Checkpoint Blockade. Immunity, 44(3), 609-621. https://doi.org/10.1016/j.immuni.2016.01.024
Poon, E., Mullins, S., Watkins, A., Williams, G. S., Koopmann, J. O., Di Genova, G., Cumberbatch, M., Veldman-Jones, M., Grosskurth, S. E., Sah, V., Schuller, A., Reimer, C., Dovedi, S. J., Smith, P. D., Stewart, R., & Wilkinson, R. W. (2017). The MEK inhibitor selumetinib complements CTLA-4 blockade by reprogramming the tumor immune microenvironment. Journal for ImmunoTherapy of Cancer, 5(1), Article 63. https://doi.org/10.1186/s40425-017-0268-8
Eng, C., Kim, T. W., Bendell, J., Argilés, G., Tebbutt, N. C., Di Bartolomeo, M., Falcone, A., Fakih, M., Kozloff, M., Segal, N. H., Sobrero, A., Yan, Y., Chang, I., Uyei, A., Roberts, L., Ciardiello, F., Ahn, J., Asselah, J., Badarinath, S., & Baijal, S. (2019). Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial. The Lancet Oncology, 20(6), 849-861. https://doi.org/10.1016/s1470-2045(19)30027-0
Corcoran, R., Giannakis, M., Allen, J., Chen, J., Pelka, K., Chao, S., Meyerhardt, J., Enzinger, A., Enzinger, P., McCleary, N., Yugelun, M., Abrams, T., Kanter, K., Van Seventer, E., Bradford, W., Fetter, I., Siravegna, G., Tian, J., Clark, J., & Ryan, D. (2020). SO-26 Clinical efficacy of combined BRAF, MEK, and PD-1 inhibition in BRAFV600E colorectal cancer patients. Annals of Oncology, 31(Suppl. 3), S226-S227. https://doi.org/10.1016/j.annonc.2020.04.041
Tabernero, J., Grothey, A., Van Cutsem, E., Yaeger, R., Wasan, H., Yoshino, T., Desai, J., Ciardiello, F., Loupakis, F., Hong, Y. S., Steeghs, N., Guren, T. K., Arkenau, H. T., Garcia-Alfonso, P., Elez, E., Gollerkeri, A., Maharry, K., Christy-Bittel, J., & Kopetz, S. (2021). Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E-Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study. Journal of Clinical Oncology, 39(4), 273-284. https://doi.org/10.1200/JCO.20.02088
Ganesh, K., Stadler, Z. K., Cercek, A., Mendelsohn, R. B., Shia, J., Segal, N. H., & Diaz, L. A., Jr. (2019). Immunotherapy in colorectal cancer: rationale, challenges and potential. Nature Reviews Gastroenterology & Hepatology, 16(6), 361-375. https://doi.org/10.1038/s41575-019-0126-x
Lenz, H.-J. J., Van Cutsem, E., Limon, M. L., Wong, K. Y., Hendlisz, A., Aglietta, M., Garcia-Alfonso, P., Neyns, B., Luppi, G., Cardin, D., Dragovich, T., Shah, U., Atasoy, A., Postema, R., Boyd, Z., Ledeine, J.-M., Overman, M., & Lonardi, S. (2018). LBA18_PR - Durable clinical benefit with nivolumab (NIVO) plus low-dose ipilimumab (IPI) as first-line therapy in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). Annals of Oncology, 29(Suppl. 8), viii714. https://doi.org/10.1093/annonc/mdy424.019
Lee, L. H., Cavalcanti, M. S., Segal, N. H., Hechtman, J. F., Weiser, M. R., Smith, J. J., Garcia-Aguilar, J., Sadot, E., Ntiamoah, P., Markowitz, A. J., Shike, M., Stadler, Z. K., Vakiani, E., Klimstra, D. S., & Shia, J. (2016). Patterns and prognostic relevance of PD-1 and PD-L1 expression in colorectal carcinoma. Modern Pathology, 29(11), 1433-1442. https://doi.org/10.1038/modpathol.2016.139
Fukuoka, S., Hara, H., Takahashi, N., Kojima, T., Kawazoe, A., Asayama, M., Yoshii, T., Kotani, D., Tamura, H., Mikamoto, Y., Hirano, N., Wakabayashi, M., Nomura, S., Sato, A., Kuwata, T., Togashi, Y., Nishikawa, H., & Shitara, K. (2020). Regorafenib Plus Nivolumab in Patients With Advanced Gastric or Colorectal Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, EPOC1603). Journal of Clinical Oncology, 38(18), 2053-2061. https://doi.org/10.1200/JCO.19.03296
Huyghe, N., Benidovskaya, E., Stevens, P., & Van den Eynde, M. (2022). Biomarkers of Response and Resistance to Immunotherapy in Microsatellite Stable Colorectal Cancer: Toward a New Personalized Medicine. Cancers, 14(9), Article 2241. https://doi.org/10.3390/cancers14092241
Schrock, A. B., Ouyang, C., Sandhu, J., Sokol, E., Jin, D., Ross, J. S., Miller, V. A., Lim, D., Amanam, I., Chao, J., Catenacci, D., Cho, M., Braiteh, F., Klempner, S. J., Ali, S. M., & Fakih, M. (2019). Tumor mutational burden is predictive of response to immune checkpoint inhibitors in MSI-high metastatic colorectal cancer. Annals of Oncology, 30(7), 1096-1103. https://doi.org/10.1093/annonc/mdz134
Huyghe, N., Baldin, P., & Van den Eynde, M. (2019). Immunotherapy with immune checkpoint inhibitors in colorectal cancer: what is the future beyond deficient mismatch - repair tumours? Gastroenterology Report, 8(1), 11-24. https://doi.org/10.1093/gastro/goz061
Marliot, F., Chen, X., Kirilovsky, A., Sbarrato, T., El Sissy, C., Batista, L., Van den Eynde, M., Haicheur-Adjouri, N., Anitei, M. G., Musina, A. M., Scripcariu, V., Lagorce-Pagès, C., Hermitte, F., Galon, J., Fieschi, J., & Pagès, F. (2020). Analytical validation of the Immunoscore and its associated prognostic value in patients with colon cancer. Journal for ImmunoTherapy of Cancer, 8(1), Article e000272. https://doi.org/10.1136/jitc-2019-000272
Chakrabarti, S., Huebner, L. J., Finnes, H. D., Muranyi, A., Clements, J., Singh, S., Hubbard, J. M., McWilliams, R. R., Shanmugam, K., & Sinicrope, F. A. (2019). Intratumoral CD3+ and CD8+ T-Cell Densities in Patients With DNA Mismatch Repair-Deficient Metastatic Colorectal Cancer Receiving Programmed Cell Death-1 Blockade. JCO Precision Oncology, 3, 1-7. https://doi.org/10.1200/PO.19.00055
Guinney, J., Dienstmann, R., Wang, X., de Reyniès, A., Schlicker, A., Soneson, C., Marisa, L., Roepman, P., Nyamundanda, G., Angelino, P., Bot, B. M., Morris, J. S., Simon, I. M., Gerster, S., Fessler, E., De Sousa E Melo, F., Missiaglia, E., Ramay, H., Barras, D., Homicsko, K., … Tejpar, S. (2015). The consensus molecular subtypes of colorectal cancer. Nature Medicine, 21(11), 1350-1356. https://doi.org/10.1038/nm.3967
Fontana, E., Eason, K., Cervantes, A., Salazar, R., & Sadanandam, A. (2019). Context matters-consensus molecular subtypes of colorectal cancer as biomarkers for clinical trials. Annals of Oncology, 30(4), 520-527. https://doi.org/10.1093/annonc/mdz052
Valero, C., Lee, M., Hoen, D., Weiss, K., Kelly, D. W., Adusumilli, P. S., Paik, P. K., Plitas, G., Ladanyi, M., Postow, M. A., Ariyan, C. E., Shoushtari, A. N., Balachandran, V. P., Hakimi, A. A., Crago, A. M., Long Roche, K. C., Smith, J. J., Ganly, I., Wong, R. J., Patel, S. G., … Morris, L. (2021). Pretreatment neutrophil-to-lymphocyte ratio and mutational burden as biomarkers of tumor response to immune checkpoint inhibitors. Nature Communications, 12(1), Article 729. https://doi.org/10.1038/s41467-021-20935-9
Downloads
Published
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)