Comprehensive meta-analysis of key immune-related adverse events from CTLA-4 and PD-1/PD-L1 inhibitors in cancer patients

Cancer Immunology Research

Volumn 5, Issue 4, 2017, Pages 312-318

  De Velasco, Guillermo ^a,b   Je, Youjin ^c   Bossé, Dominick ^a   Awad, Mark M ^a   Ott, Patrick A ^a   Moreira, Raphael B ^a   Schutz, Fabio ^d   Bellmunt, Joaquim ^a   Sonpavde, Guru P ^e   Hodi, F Stephen ^a   Choueiri, Toni K ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b University Hospital   (Spain)

^c Kyung Hee University   (South Korea)

^d HOSPITAL SÃO JOSÉ   (Brazil)

^e UNIVERSITY OF ALABAMA SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ASPARTATE AMINOTRANSFERASE; ATEZOLIZUMAB; IPILIMUMAB; NIVOLUMAB; PEMBROLIZUMAB;

ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; CANCER IMMUNOTHERAPY; CANCER PATIENT; COLITIS; CONTROLLED STUDY; HUMAN; HYPERTRANSAMINASEMIA; HYPOTHYROIDISM; INCIDENCE; META ANALYSIS; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PNEUMONIA; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; RISK FACTOR;

EID: 85017283935     PISSN: 23266066     EISSN: 23266074     Source Type: Journal    
DOI: 10.1158/2326-6066.CIR-16-0237     Document Type: Article

References (47)

1. Powles T, Eder JP, Fine GD, Braiteh FS, Loriot Y, Cruz C, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 2014;515:558-62.
2. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012;366:2443-54.
3. Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015;373:1803-13.
4. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015;373:1979-1979.
5. Nghiem PT, Bhatia S, Lipson EJ, Kudchadkar RR, Miller NJ, Annamalai L, et al. PD-1 blockade with pembrolizumab in advanced Merkel-cell carcinoma. N Engl J Med 2016;374:2542-52.
6. Ledford H. Melanoma drug wins US approval. Nature 2011;471:561.
7. U. S. Food and Drug Administration, Center for Drug Evaluation and Research. Atezolizumab BLA 761041 approval letter, October 18, 2016. Retrieved February 2, 2017, from http://www.accessdata.fda.gov/drugsatf da-docs/appletter/2016/761041Orig1s000ltr.pdf
8. Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 2011;364:2517-26.
9. Weber JS, Kähler KC, Hauschild A. Management ofimmune-related adverse events and kinetics of responsewith ipilimumab. J Clin Oncol Off JAmSoc Clin Oncol 2012;30:2691-7.
10. Chen TW, Razak AR, Bedard PL, Siu LL, Hansen AR. A systematic review of immune-related adverse event reporting in clinical trials of immune checkpoint inhibitors. J Clin Oncol 2014;32; 5 Suppl: Abstract 3057.
11. Voskens CJ, Goldinger SM, Loquai C, Robert C, Kaehler KC, Berking C, et al. The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy inmetastatic melanoma from the ipilimumab network. Soyer HP, editor. PLoS ONE 2013;8:e53745.
12. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients withmetastatic melanoma. N Engl J Med 2010;363:711-23.
13. Minkis K, Garden BC, Wu S, Pulitzer MP, Lacouture ME. The risk of rash associated with ipilimumab in patients with cancer: a systematic review of the literature and meta-analysis. J Am Acad Dermatol 2013;69:e121-128.
14. Bernardo SG, Moskalenko M, Pan M, Shah S, Sidhu HK, Sicular S, et al. Elevated rates of transaminitis during ipilimumab therapy for metastatic melanoma. Melanoma Res 2013;23:47-54.
15. Ibrahim R. A., Berman D. M., DePril V.. Ipilimumab safety profile: Summary of findings from completed trials in advanced melanoma. J Clin Oncol 2011;29:(suppl; abstr 8583); Available from: http://ascopubs.org/doi/abs/10.1200/jco.2011.29.15-suppl.8583.
16. Pagès C, Gornet JM, Monsel G, Allez M, Bertheau P, Bagot M, et al. Ipilimumab-induced acute severe colitis treated by infliximab. Melanoma Res 2013;23:227-30.
17. 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 Off J Eur Soc Med Oncol ESMO 2015;26:2375-91.
18. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-88.
19. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629-34.
20. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994;50:1088-101.
21. Beer TM, Kwon ED, Drake CG, Fizazi K, Logothetis C, Gravis G, et al. Randomized, double-blind, phase III trial of ipilimumab versus placebo in asymptomatic or minimally symptomatic patients with metastatic chemotherapynaive castration-resistant prostate cancer. J Clin Oncol 2017;35:40-47.
22. Reck M, Luft A, Szczesna A, Havel L, Kim S-W, Akerley W, et al. Phase III randomized trial of ipilimumab plus etoposide and platinum versus placebo plus etoposide and platinum in extensive-stage small-cell lung cancer. J Clin Oncol 2016;34:3740-48.
23. Eggermont AM, Chiarion-Sileni V, Grob J-J, Dummer R, Wolchok JD, Schmidt H, et al. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol 2015;16:522-530.
24. Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, van den Eertwegh AJM, et al. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, doubleblind, phase 3 trial. Lancet Oncol 2014;15:700-12.
25. Reck M, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, et al. Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol 2013;24:75-83.
26. Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, et al. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV Non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol 2012;30:2046-54.
27. Ferris RL, Blumenschein G, Fayette J, Guigay J, Colevas AD, Licitra L, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 2016;375:1856-67.
28. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015;372:2521-32.
29. 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 randomised, controlled, open-label, phase 3 trial. Lancet Oncol 2015;16:375-384.
30. Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WEE, Poddubskaya E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-smallcell lung cancer. N Engl J Med 2015;373:123-35.
31. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 2015;373:1627-39.
32. Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015;373:1803-13.
33. Herbst RS, Baas P, Kim D-W, Felip E, Pérez-Gracia JL, Han J-Y, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. The Lancet 2016;387:1540-50.
34. Langer CJ, Gadgeel SM, Borghaei H, Papadimitrakopoulou VA, Patnaik A, Powell SF, et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol 2016;17:1497-508.
35. Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csóśzi T, Fülöp A, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016;375:1823-33.
36. Ribas A, Puzanov I, Dummer R, Schadendorf D, Hamid O, Robert C, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumabrefractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol 2015;16:908-918.
37. Bellmunt J, de Wit R, Vaughn D, Fradet Y, Lee J, Fong L. Keynote-045: openlabel, phase III study of pembrolizumab versus investigator's choice of paclitaxel, docetaxel, or vinflunine for previously treated advanced urothelial cancer. J Immuno Ther Cancer 2016, 4:O2; 2016.
38. Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, et al. Atezolizumab versus docetaxel for patientswith previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet 2016;387:1837-46.
39. Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, et al. Atezolizumab versus docetaxel in patients with previously treated nonsmallcell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet 2017;389:255-65.
40. Amin A, Plimack ER, Infante JR, Ernstoff MS, Rini B, McDermott DF, et al. Nivolumab (anti-PD-1; BMS-936558, ONO-4538) in combination with sunitinib or pazopanib in patients (pts) with metastatic renal cell carcinoma (mRCC). J Clin Oncol 2014;32:5s.
41. McDermott DF, Infante JR, Voss MH, Motzer RJ, Haanen JB, Chowdhury S, et al. A phase I/II study to assess the safety and efficacy of pazopanib and MK-3475 in subjects with advanced renal cell carcinoma. J Clin Oncol 2014;32:5s.
42. Atkins MB, Gupta S, Choueiri TK, McDermott DF, Puzanov I, Tarazi J, et al. Phase Ib dose-finding study of axitinib plus pembrolizumab in treatment naïve patients with advanced renal cell carcinoma. J Immunother Cancer 2015;3:P353.
43. Atkinson BJ, Cauley DH, Ng C, Millikan RE, Xiao L, Corn P, et al. Mammalian target of rapamycin (mTOR) inhibitor-associated non-infectious pneumonitis in patients with renal cell cancer: predictors, management, and outcomes. BJU Int 2014;113:376-82.
44. Dabydeen DA, Jagannathan JP, Ramaiya N, Krajewski K, Schutz FAB, Cho DC, et al. Pneumonitis associated with mTOR inhibitors therapy in patients with metastatic renal cell carcinoma: incidence, radiographic findings and correlation with clinical outcome. Eur J Cancer Oxf Engl 1990 2012;48:1519-24.
45. Schroll JB, Maund E, Gøtzsche PC. Challenges in coding adverse events in clinical trials: a systematic review. PloS ONE 2012;7:e41174.
46. Bennett CL, Silver SM, Djulbegovic B, Samaras AT, Blau CA, Gleason KJ, et al. Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anemia. JAMA 2008;299:914-24.
47. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015;373:23-34.