Clinical applications of PD-1-based therapy: A focus on pembrolizumab (MK-3475) in the management of melanoma and other tumor types

OncoTargets and Therapy

Volumn 8, Issue , 2015, Pages 929-937

  Gangadhar, Tara C ^a   Salama, April Ks ^b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Antitumor activity; Cancer; Immunotherapy; Nivolumab; PD 1; Pembrolizumab

Indexed keywords

DACARBAZINE; DEXAMETHASONE; DOCETAXEL; IPILIMUMAB; LENALIDOMIDE; NIVOLUMAB; PEMBROLIZUMAB; PROGRAMMED DEATH 1 RECEPTOR;

ADVANCED CANCER; ANTINEOPLASTIC ACTIVITY; ARTHRALGIA; ARTICLE; CASTRATION RESISTANT PROSTATE CANCER; COLORECTAL CANCER; DECREASED APPETITE; DIARRHEA; DOSAGE SCHEDULE COMPARISON; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPNEA; ELIMINATION HALF-LIFE; FATIGUE; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HEADACHE; HEMATOLOGIC MALIGNANCY; HUMAN; HYPERTRANSAMINASEMIA; HYPOTHYROIDISM; KIDNEY CARCINOMA; LOW DRUG DOSE; MELANOMA; METASTATIC COLORECTAL CANCER; MULTIPLE MYELOMA; NAUSEA; NON SMALL CELL LUNG CANCER; OVERALL SURVIVAL; PERICARDIAL EFFUSION; PNEUMONIA; PROGRESSION FREE SURVIVAL; PRURITUS; RASH; REGULATORY T LYMPHOCYTE; SOLID TUMOR; SURVIVAL RATE; T LYMPHOCYTE ACTIVATION; TUMOR REGRESSION; UROGENITAL TRACT CANCER;

EID: 84929411847     PISSN: 11786930     EISSN: 11786930     Source Type: Journal    
DOI: 10.2147/OTT.S53164     Document Type: Article

References (67)

1. Rosenberg SA, Yang JC, Topalian SL, et al. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA. 1994;271(12):907–913.
2. Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol. 1996;14(1):7–17.
3. Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–723.
4. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363(5):411–422.
5. Zajac AJ, Blattman JN, Murali-Krishna K, et al. Viral immune evasion due to persistence of activated T cells without effector function. J Exp Med. 1998;188(12):2205–2213.
6. Wherry EJ. T cell exhaustion. Nat Immunol. 2011;12(6):492–499.
7. Virgin HW, Wherry EJ, Ahmed R. Redefining chronic viral infection. Cell. 2009;138(1):30–50.
8. Barber DL, Wherry EJ, Masopust D, et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. 2006;439(7077):682–687.
9. Trautmann L, Janbazian L, Chomont N, et al. Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nat Med. 2006;12(10):1198–1202.
10. Francisco LM, Salinas VH, Brown KE, et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med. 2009;206(13):3015–3029.
11. Day CL, Kaufmann DE, Kiepiela P, et al. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature. 2006;443(7109):350–354.
12. Petrovas C, Casazza JP, Brenchley JM, et al. PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection. J Exp Med. 2006;203(10):2281–2292.
13. Parry RV, Chemnitz JM, Frauwirth KA, et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol Cell Biol. 2005;25(21):9543–9553.
14. KEYTRUDA® (pembrolizumab) [package insert]. Whitehouse Station, NJ: Merck; 2014. Accessed November 26, 2014.
15. Hamid O. Efficacy and safety of MK-3475 in patients with advanced melanoma. Presented at: The Society for Melanoma Research 2012 Congress, Hollywood, CA, November 8–11, 2012.
16. Hamid O, Robert C, Daud A, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013;369(2):134–144.
17. Robert C, Ribas A, Wolchok JD, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014;384(9948):1109–1117.
18. Hamid O, Robert C, Ribas A, et al. Randomized comparison of two doses of the anti-PD-1 monoclonal antibody MK-3475 for ipilimumab-refractory (IPI-R) and IPI-naive (IPI-N) melanoma (MEL) [abstr 3000]. J Clin Oncol. 2014;32(Suppl):5S.
19. Ribas A, Hodi FS, Kefford R, et al. Efficacy and safety of the anti-PD-1 monoclonal antibody MK-3475 in 411 patients (pts) with melanoma (MEL) [abstr LBA9000]. J Clin Oncol. 2014;32(Suppl):5S.
20. Joseph RW, Elassaiss-Schaap J, Wolchok J, et al. Baseline tumor size as an independent prognostic factor for overall survival in patients with metastatic melanoma treated with the anti-PD-1 monoclonal antibody MK-3475 [abstr 3015]. J Clin Oncol. 2014;32(Suppl):5S.
21. Wolchok JD, Hoos A, O’Day S, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009;15(23):7412–7420.
22. Hodi FS, Ribas A, Daud A, et al. Evaluation of immune-related response criteria (irRC) in patients (pts) with advanced melanoma (MEL) treated with the anti-PD-1 monoclonal antibody MK-3475 [abstr 3006]. J Clin Oncol. 2014;32(Suppl):5S.
23. Ribas A, Puzanov I, Dummer R, et al. A randomized controlled comparison of pembrolizumab and chemotherapy in patients with ipilimumab-refractory melanoma. Presented at: Society for Melanoma Research 2014 International Congress, Zurich, Switzerland, 13–16 November, 2014.
24. Topalian SL, Sznol M, McDermott DF, et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014;32(10):1020–1030.
25. Wolchok JD, Kluger H, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369(2):122–133.
26. Douillard JY, Shepherd FA, Hirsh V, et al. Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial. J Clin Oncol. 2010;28(5):744–752.
27. Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363(18):1693–1703.
28. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947–957.
29. Shaw AT, Ou SH, Bang YJ, et al. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 2014;371(21):1963–1971.
30. Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011;12(8):735–742.
31. Al-Moundhri M, O’Brien M, Souberbielle BE. Immunotherapy in lung cancer. Br J Cancer. 1998;78(3):282–288.
32. Salgaller ML. The development of immunotherapies for non-small cell lung cancer. Expert Opin Biol Ther. 2002;2(3):265–278.
33. Lynch TJ, Bondarenko I, Luft A, 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(17): 2046–2054.
34. Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366(26):2455–2465.
35. Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–2454.
36. Yang CY, Lin MW, Chang YL, Wu CT, Yang PC. Programmed cell death-ligand 1 expression in surgically resected stage I pulmonary adenocarcinoma and its correlation with driver mutations and clinical outcomes. Eur J Cancer. 2014;50(7):1361–1369.
37. Velcheti V, Schalper KA, Carvajal DE, et al. Programmed death ligand-1 expression in non-small cell lung cancer. Lab Invest. 2014;94(1):107–116.
38. Boland JM, Kwon ED, Harrington SM, et al. Tumor B7-H1 and B7-H3 expression in squamous cell carcinoma of the lung. Clin Lung Cancer. 2013;14(2):157–163.
39. Konishi J, Yamazaki K, Azuma M, Kinoshita I, Dosaka-Akita H, Nishimura M. B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression. Clin Cancer Res. 2004;10(15):5094–5100.
40. Velcheti V, Rimm DL, Schalper KA. Sarcomatoid lung carcinomas show high levels of programmed death ligand-1 (PD-L1). J Thorac Oncol. 2013;8(6):803–805.
41. Chen YB, Mu CY, Huang JA. Clinical significance of programmed death-1 ligand-1 expression in patients with non-small cell lung cancer: a 5-year-follow-up study. Tumori. 2012;98(6):751–755.
42. Mu CY, Huang JA, Chen Y, Chen C, Zhang XG. High expression of PD-L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation. Med Oncol. 2011;28(3):682–688.
43. Brahmer JR, Horn L, Antonia S, et al. Nivolumab (anti-PD-1; BMS-936558; ONO-4538) in patients with non-small cell lung cancer (NSCLC): overall survival and long-term safety in a phase 1 trial. Presented at: IASLC 15th World Conference on Lung Cancer, Sydney, Australia, October 22–30, 2013.
44. Garon EB, Leighl NB, Rizvi NA, et al. Safety and clinical activity of MK-3475 in previously treated patients (pts) with non-small cell lung cancer (NSCLC). Presented at: The American Society of Clinical Oncology Annual Meeting, Chicago, IL, USA, October 22–30, 2013.
45. Rizvi NA, Garon EB, Patnaik A, et al. Safety and clinical activity of MK-3475 as initial therapy in patients with advanced non-small cell lung cancer (NSCLC). Presented at: The American Society of Clinical Oncology Annual Meeting, Chicago, IL, USA, May 30–June 3, 2014.
46. Fyfe G, Fisher RI, Rosenberg SA, Sznol M, Parkinson DR, Louie AC. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol. 1995;13(3):688–696.
47. Fisher RI, Rosenberg SA, Fyfe G. Long-term survival update for high-dose recombinant interleukin-2 in patients with renal cell carcinoma. Cancer J Sci Am. 2000;6(Suppl 1):S55–S57.
48. Escudier B, Porta C, Schmidinger M, et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(Suppl 3):349–356.
49. Coppin C, Le L, Porzsolt F, Wilt T. Targeted therapy for advanced renal cell carcinoma. Cochrane Database Syst Rev. 2008;(2):CD006017.
50. Thompson RH, Dong H, Lohse CM, et al. PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma. Clin Cancer Res. 2007;13(6):1757–1761.
51. Finke JH, Rayman PA, Ko JS, Bradley JM, Gendler SJ, Cohen PA. Modification of the tumor microenvironment as a novel target of renal cell carcinoma therapeutics. Cancer J. 2013;19(4):353–364.
52. Ko JS, Zea AH, Rini BI, et al. Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res. 2009;15(6):2148–2157.
53. Sfanos KS, Bruno TC, Maris CH, et al. Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing. Clin Cancer Res. 2008;14(11):3254–3261.
54. Ebelt K, Babaryka G, Frankenberger B, et al. Prostate cancer lesions are surrounded by FOXP3+, PD-1+ and B7-H1+ lymphocyte clusters. Eur J Cancer. 2009;45(9):1664–1672.
55. Slovin SF, Higano CS, Hamid O, et al. Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: results from an open-label, multicenter phase I/II study. Ann Oncol. 2013;24(7):1813–1821.
56. Brandwein-Gensler M, Smith RV. Prognostic indicators in head and neck oncology including the new 7th edition of the AJCC staging system. Head Neck Pathol. 2010;4(1):53–61.
57. Mell LK, Dignam JJ, Salama JK, et al. Predictors of competing mortality in advanced head and neck cancer. J Clin Oncol. 2010;28(1):15–20.
58. Brockstein BE, Vokes EE. Head and neck cancer in 2010: maximizing survival and minimizing toxicity. Nat Rev Clin Oncol. 2011;8(2):72–74.
59. Seiwert T, Burtness B, Weiss J, et al. A phase Ib study of MK-3475 in patients with human papillomavirus (HPV)-associated and non-HPV–associated head and neck (H/N) cancer [abstr 6011]. J Clin Oncol. 2014;32(Suppl):5S.
60. Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8(8):793–800.
61. Gatalica Z, Snyder CL, Yeats K, Xiao N, Holterman D, Lynch HT. Programmed death 1 (PD-1) lymphocytes and ligand (PD-L1) in colorectal cancer and their relationship to microsatellite instability status [abstr 3625]. J Clin Oncol. 2014;32(Suppl):5S.
62. Droeser RA, Hirt C, Viehl CT, et al. Clinical impact of programmed cell death ligand 1 expression in colorectal cancer. Eur J Cancer. 2013;49(9):2233–2242.
63. Brahmer JR, Drake CG, Wollner I, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010;28(19):3167–3175.
64. Lipson EJ, Sharfman WH, Drake CG, et al. Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody. Clin Cancer Res. 2013;19(2):462–468.
65. Sznol M, Chen L. Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer–response. Clin Cancer Res. 2013;19(19):5542.
66. Berger R, Rotem-Yehudar R, Slama G, et al. Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies. Clin Cancer Res. 2008;14(10):3044–3051.
67. Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–330.