What do we know about cancer immunotherapy? Long-term survival and immune-related adverse events

Main Article Content

Jesus Miranda Poma
Lorena Ostios Garcia
Julia Villamayor Sanchez
Gabriele D’errico

Keywords

Immunotherapy, Adverse events, Management, Response rates

Abstract

Immunotherapy delivered a new therapeutic option to the oncologist: Ipilimumab (anti-CTLA-4), Nivolumab and Pembrolizumab (anti-PD1), and Atezolizumab (anti-PD-L1) increase overall survival and show a better safety profile compared to chemotherapy in patients with metastatic melanoma, lung, renal cancer among others. But all that glitters is not gold and there is an increasing number of reports of adverse effects while using immune-checkpoint inhibitors. While chemotherapy could weaken the immune system, this novel immunotherapy could hyper-activate it, resulting in a unique and distinct spectrum of adverse events, called immune-related adverse events (IRAEs). IRAEs, ranging from mild to potentially life-threatening events, can involve many systems, and their management is radically different from that of cytotoxic drugs: immunosuppressive treatments, such as corticoids, infliximab or mycophenolate mofetil, usually result in complete reversibility, but failing to do so can lead to severe toxicity or even death. Patient selection is an indirect way to reduce adverse events minimizing the number of subjects exposed to this drugs: unfortunately PDL-1, the actual predictive biomarker, would not allow clinicians select or exclude patients for treatment with checkpoint inhibitors.

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References

1. Kumar V, Chaudhary N, Garg M, Floudas CS, Soni P, Chandra AB. Current diagnosis and management of immune-related adverse events (IRAEs) induced by immune checkpoint inhibitor therapy. Front Pharmacol. 2017;8:49, http://dx.doi.org/10.3389/fphar.2017.00049.

2. Weber JS, Hodi FS, Wolchok JD, Topalian SL, Schadendorf D, Larkin J, et al. Safety profile of nivolumab monotherapy: a pooled analysis of patients with advanced melanoma. J Clin Oncol [Internet]. 2017;35:785-92. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28068177

3. Larkin J, Hodi FS, Wolchok JD. Combined Nivolumab and Ipilimumab or monotherapy in untreated melanoma. N Engl J Med [Internet]. 2015;373:1---1270. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26398076

4. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med [Internet]. 2010;363:711-23. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20525992

5. Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, et al. Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol [Internet]. 2015;33:1889-94. Available from: http://jco.ascopubs.org/cgi/doi/10.1200/JCO.2014.56.2736%5Cn http://www.ncbi.nlm.nih.gov/pubmed/25667295

6. Eggermont AMM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, et al. Adjuvant Ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomized, double-blind, phase 3 trial. Lancet Oncol. 2015;16:522-30.

7. Weber JS, D’Angelo SP, Minor D, Hodi FS, Gutzmer R, Neyns B, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomized, controlled, open-label, phase 3 trial. Lancet Oncol. 2015;16:375-84.

8. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus Ipilimumab in advanced melanoma. N Engl J Med [Internet]. 2015;372:2521-32. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa1503093

9. Champiat S, Lambotte O, Barreau E, Belkhir R, Berdelou A, Carbonnel F. Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper. Ann. Oncol. 2016;27:559-74.

10. Naidoo J, Page DB, Li BT, Connell LC, Schindler K, Lacouture ME, et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann. Oncol. 2015;26:2375-91.

11. Langer CJ. Emerging immunotherapies in the treatment of non-small cell lung cancer (NSCLC). Am J Clin Oncol [Internet]. 2015;38:422-30. Available from: http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00000421-201508000-00018

12. Michot JM, Bigenwald C, Champiat S, Collins M. ScienceDirect immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer [Internet]. 2017;54:139-48, http://dx.doi.org/10.1016/j.ejca.2015.11.016.

13. Tie Y, Ma X, Zhu C, Mao Y, Shen K, Wei X, et al. Safety and efficacy of nivolumab in the treatment of cancers: a meta-analysis of 27 prospective clinical trials. Int J cancer [Internet]. 2017;140:948-58. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27813059

14. Marrone KA, Ying W, Naidoo J. Immune-related adverse events from immune checkpoint inhibitors. Clin Pharmacol Ther [Internet]. 2016;100:242-51. Available from: http://doi.wiley.com/10.1002/cpt.394

15. Della Vittoria Scarpati G, Fusciello C, Perri F, Sabbatino F, Ferrone S, Carlomagno C, et al. Ipilimumab in the treatment of metastatic melanoma: management of adverse events. Onco Targets Ther. 2014;7:203-9.

16. Beck KE, Blansfield JA, Tran KQ, Feldman AL, Hughes MS, Royal RE, et al. Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4. J. Clin. Oncol. 2006;24:2283-9.

17. Horvat TZ, Adel NG, Dang T, Momtaz P, Postow MA, Callahan MK, et al. Immune-related adverse events need for systemic immunosuppression, and effects on survival and time to treatment failure in patients with melanoma treated with ipilimumab at memorial Sloan Kettering Cancer Center. 2015;33.