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Immunotherapy of Colorectal and Anal Carcinoma


Authors: J. Tomášek;  I. Kiss
Authors‘ workplace: Klinika komplexní onkologické péče, Masarykův onkologický ústav, Brno
Published in: Klin Onkol 2017; 30(Supplementum3): 62-65
Category: Review
doi: https://doi.org/10.14735/amko20173S62

Overview

Background:
The lower part of the digestive tract includes the large intestine, rectum and anus. Treatment algorithms of cancers in these localities have significant differences in both early and advanced stages. The vast majority of metastatic cases are incurable. A few years ago, it was generally accepted that gastrointestinal tumors are poorly immunogenic and modern immunotherapy would not work in gastrointestinal cancers. The breakthrough has become the recognition of the mismatch repair system (MMR) that affects the microsatellite instability (MSI) and it‘s role in the development of colorectal carcinoma (CRC). Metastatic colorectal carcinoma (mCRC) with defect MMR (dMMR) and MSI-H, resp. is immunogenic and can be a target of modern imunotherapy directed on the PD1/PD-L1 axis. Such a treatment can improve prognosis and life quality od patients with mCRC MSI-H. Immunotherapy effectiveness was shown also in a subgroup of patients with a BRAF mutation where the effectiveness of existing systemic treatment is low. The proven predictive factor is dMMR/MSI-H. PD-1 expression does not have this significance. Results of clinical studies with nivolumab and pembrolizumab result in the inclusion of these drugs in mCRC treatment algorithms. Phase II study shows nivolumab effectiveness also in pretreated metastatic anal cancer.

Purpose:
An overview of basic information on the possibilities of immunotherapy in CRC and anal cancers.

Key words:
cancer immunotherapy – checkpoint inhibitors – colorectal cancer – anal cancer – nivolumab – pembrolizumab

Supported by MH CZ – DRO (MMCI, 00209805)

I declare that, in connection with the abovementioned contribution, which I am an author, I have a conflict of interest with the following companies: BMS, Roche, Merck, Amgem and Bayer.

The author declares he has no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted:
7. 9. 2017

Accepted:
5. 11. 2017


Sources

1. National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer stat facts: colon and rectum cancer. [online]. Available from: http: //seer.cancer.gov/statfacts/html/colorect.html.

2. Llosa NJ, Cruise M, Tam A et al. The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov 2015; 5 (1): 43–51. doi: 10.1158/2159-8290.CD-14-0863.

3. Galon J, Costes A, Sanchez-Cabo F et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006; 313 (5795): 1960–1964. doi: 10.1126/science.1129139.

4. Pages F, Berger A, Camus M et al. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 2005; 353 (25): 2654–2666. doi: 10.1056/NEJMoa051424.

5. Závadová E, Špaček J, Vočka M et al. Imunoscore a jeho prediktivní hodnota u kolorektálního karcinomu. Klin Onkol 2015; 28 (Suppl 4): 82–85. doi: 0.14735/amko20154S82.

6. Le DT, Uram JN, Wang H et al. Programmed death-1 blockade in mismatch repair deficient colorectal cancer. J Clin Oncol 2016; 34 (Suppl 15): abstr 103.

7. National Comprehensive Cancer Network. Guidelines Version 2.2017 Colon Cancer. [online]. Available from: https: //www.nccn.org/professionals/physician_gls/default.aspx.

8. O‘Neil BH, Wallmark J, Lorente D et al. Pembrolizumab (MK-3475) for patients with advanced colorectal carcinoma (CRC): Preliminary results from KEYNOTE-028. Eur J Cancer 2015; 51 (Suppl 3): abstr 502. doi: 10.1016/S0959-8049 (16) 30304-5.

9. Postow MA, Chesney J, Pavlick AC et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med 2015; 372 (21): 2006–2017. doi: 10.1056/NEJMoa1414428.

10. Overman MJ, Kopetz S, McDermott RS et al. Nivolumab ± ipilimumab in treatment (tx) of patients (pts) with metastatic colorectal cancer (mCRC) with and without high microsatellite instability (MSI-H): CheckMate-142 interim results. J Clin Oncol 2016; 34 (Suppl 15): abstr 3501. doi: 10.1200/JCO.2016.34.15_suppl.3501.

11. 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.

12. Morris VK, Salem ME, Nimeiri H et al. Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study. Lancet Oncol 2017; 18 (4): 446–453. doi: 10.1016/S1470-2045 (17) 30104-3.

13. Ott PA, Piha-Paul SA, Munster P et al. Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ann Oncol 2017; 28 (5): 1036–1041. doi: 10.1093/annonc/mdx 029.

14. Avelumab for MSI-H or POLE Mutated Metastatic Colorectal Cancer. ClinicalTrials.gov. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT03150706.

15. An Investigational Immuno-therapy Study of Nivolumab, and Nivolumab in Combination With Other Anti-cancer Drugs, in Colon Cancer That Has Come Back or Has Spread (CheckMate142). ClinicalTrials.gov. [online]. Available from: https: / / clinicaltrials.gov/ ct2/ show/ NCT02060188.

16. A study to investigate efficacy and safety of cobimetinib plus atezolizumab and atezolizumab monotherapy versus regorafenib in participants with metastatic colorectal adenocarcinoma. ClinicalTrials.gov. [online]. Available from: https: / / clinicaltrials.gov/ ct2/ show/ NCT02788279.

17. A Study Evaluating TAS-102 Plus Nivolumab in Patients With MSS CRC. ClinicalTrials.gov. [online]. Available from: https: / / clinicaltrials.gov/ ct2/ show/ NCT02860

546.

18. Study of Pembrolizumab in Combination With Chemotherapy for Patients With Advanced Colorectal Cancer. ClinicalTrials.gov [online]. Available from: https: / / clinicaltrials.gov/ ct2/ show/ NCT02375672.

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Paediatric clinical oncology Surgery Clinical oncology
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