Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: A comprehensive review of registration trials and future considerations

Journal for ImmunoTherapy of Cancer

Volumn 6, Issue 1, 2018, Pages

  Gong, Jun ^a   Chehrazi Raffle, Alexander ^b   Reddi, Srikanth ^b   Salgia, Ravi ^a  

^a CITY OF HOPE NATIONAL MEDICAL CENTER   (United States)

^b HARBOR UCLA MEDICAL CENTER   (United States)

Author keywords

Biomarkers; Clinical trials; Hyperprogressors; Immune checkpoint; Immune related toxicity; Microbiome; PD 1 inhibitor; PD L1 inhibitor; Treatment beyond progression

Indexed keywords

ATEZOLIZUMAB; AVELUMAB; BIOLOGICAL MARKER; CARBOPLATIN; DURVALUMAB; GEMCITABINE; IMMUNOGLOBULIN G4; IPILIMUMAB; NIVOLUMAB; PACLITAXEL; PEMBROLIZUMAB; PEMETREXED; PLATINUM; PROGRAMMED DEATH 1 RECEPTOR; MONOCLONAL ANTIBODY;

CANCER IMMUNOTHERAPY; CELLULAR IMMUNITY; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HODGKIN DISEASE; HUMAN; MALIGNANT NEOPLASM; MERKEL CELL CARCINOMA; METASTATIC MELANOMA; MICROSATELLITE INSTABILITY; MULTICENTER STUDY (TOPIC); NON SMALL CELL LUNG CANCER; NONHUMAN; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RENAL CELL CARCINOMA; REVIEW; STOMACH CANCER; TRANSITIONAL CELL CARCINOMA; TREATMENT DURATION; IMMUNOLOGY; IMMUNOTHERAPY; METABOLISM; NEOPLASM; PROCEDURES; REGISTER;

ANTIBODIES, MONOCLONAL; HUMANS; IMMUNOTHERAPY; NEOPLASMS; PROGRAMMED CELL DEATH 1 RECEPTOR; REGISTRIES;

EID: 85040860527     PISSN: None     EISSN: 20511426     Source Type: Journal    
DOI: 10.1186/s40425-018-0316-z     Document Type: Review

References (94)

1. Agata Y, Kawasaki A, Nishimura H, Ishida Y, Tsubata T, Yagita H, et al. Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int Immunol. 1996;8:765-72.
2. Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992;11:3887-95.
3. Nishimura H, Nose M, Hiai H, Minato N, Honjo T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity. 1999;11:141-51.
4. Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192:1027-34.
5. Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999;5:1365-9.
6. Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol. 2005;23:515-48.
7. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8:793-800.
8. Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A. 2002;99:12293-7.
9. Patnaik A, Kang SP, Rasco D, Papadopoulos KP, Elassaiss-Schaap J, Beeram M, et al. Phase I study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in patients with advanced solid tumors. Clin Cancer Res. 2015;21:4286-93.
10. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366:2455-65.
11. 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.
12. Balar AV, Weber JS. PD-1 and PD-L1 antibodies in cancer: current status and future directions. Cancer Immunol Immunother. 2017;66:551-64.
13. Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013;369:134-44.
14. Robert C, Ribas A, Wolchok JD, Hodi FS, Hamid O, Kefford R, 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;384:1109-17.
15. Ribas A, Wolchok JD, Robert C, Kefford R, Hamid O, Daud A, et al. P0116 updated clinical efficacy of the anti-PD-1 monoclonal antibody pembrolizumab (MK-3475) in 411 patients with melanoma [abstract]. Eur J Cancer. 2015;51:Abstr nr P0116.
16. 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.
17. Ribas A, Puzanov I, Dummer R, Schadendorf D, Hamid O, Robert C, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015;16:908-18.
18. 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;16:375-84.
19. Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015;372:2006-17.
20. 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.
21. Sul J, Blumenthal GM, Jiang X, He K, Keegan P, Pazdur R. FDA approval summary: Pembrolizumab for the treatment of patients with metastatic non-small cell lung cancer whose tumors express programmed death-ligand 1 [abstract]. Oncologist. 2016;21:643-50.
22. Hui R, Gandhi L, Costa EC, Felip E, Ahn MJ, Eder JP, et al. Long-term OS for patients with advanced NSCLC enrolled in the KEYNOTE-001 study of pembrolizumab (pembro). J Clin Oncol. 2016;34:Abstr nr 9026.
23. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372:2018-28.
24. Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387:1540-50.
25. Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csoszi 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.
26. 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.
27. Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373:123-35.
28. 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.
29. Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, et al. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016;387:1837-46.
30. Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389:255-65.
31. Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2017;377:1919-29.
32. Balar AV, Castellano D, O'Donnell PH, Grivas P, Vuky J, Powles T, et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2017; https://doi.org/10.1016/S1470-2045(1017)30616-30612.
33. Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med. 2017;376:1015-26.
34. Sharma P, Retz M, Siefker-Radtke A, Baron A, Necchi A, Bedke J, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017;18:312-22.
35. Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016;387:1909-20.
36. Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017;389:67-76.
37. Massard C, Gordon MS, Sharma S, Rafii S, Wainberg ZA, Luke J, et al. Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. J Clin Oncol. 2016;34:3119-25.
38. Hahn NM, Powles T, Massard C, Arkenau HT, Friedlander TW, Hoimes CJ, et al. Updated efficacy and tolerability of durvalumab in locally advanced or metastatic urothelial carcinoma (UC) [abstract]. J Clin Oncol. 2017;35:Abstr nr 4525.
39. Apolo AB, Infante JR, Balmanoukian A, Patel MR, Wang D, Kelly K, et al. Avelumab, an anti-programmed death-ligand 1 antibody, in patients with refractory metastatic urothelial carcinoma: results from a multicenter, phase Ib study. J Clin Oncol. 2017;35:2117-24.
40. Apolo AB, Ellerton JA, Infante JR, Agrawal M, Gordon MS, Aljumaily R, et al. Updated efficacy and safety of avelumab in metastatic urothelial carcinoma (mUC): pooled analysis from 2 cohorts of the phase 1b Javelin solid tumor study [abstract]. J Clin Oncol. 2017;35:Abstr nr 4528.
41. 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.
42. Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol. 2016;17:956-65.
43. 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.
44. Chen R, Zinzani PL, Fanale MA, Armand P, Johnson NA, Brice P, et al. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic hodgkin lymphoma. J Clin Oncol. 2017;35:2125-32.
45. Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015;372:311-9.
46. Younes A, Santoro A, Shipp M, Zinzani PL, Timmerman JM, Ansell S, et al. Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol. 2016;17:1283-94.
47. Diaz LA, Marabelle A, Delord JP, Shapira-Frommer R, Geva R, Peled N, et al. Pembrolizumab therapy for microsatellite instability high (MSI-H) colorectal cancer (CRC) and non-CRC [abstract]. J Clin Oncol. 2017;35:Abstr nr 3071.
48. Diaz LA, Uram JN, Wang H, Bartlett B, Kemberling H, Eyring A, et al. Programmed death-1 blockade in mismatch repair deficient cancer independent of tumor histology [abstract]. J Clin Oncol. 2016;34:Abstr nr 3003.
49. Fader AN, Diaz LA, Armstrong DK, Tanner EJ, Uram J, Eyring A, et al. Preliminary results of a phase II study: PD-1 blockade in mismatch repair-deficient, recurrent or persistent endometrial cancer. Gynecol Oncol. 2016;141:206-7.
50. Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, et al. Mismatch-repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017; pii(eaan6733): https://doi.org/10.1126/science.aan6733.
51. Le DT, Uram JN, Wang H, Bartlett B, Kemberling H, Eyring A, et al. Programmed death-1 blockade in mismatch repair deficient colorectal cancer [abstract]. J Clin Oncol. 2016;34:Abstr nr 103.
52. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509-20.
53. Le DT, Uram JN, Wang H, Kemberling H, Eyring A, Bartlett B, et al. PD-1 blockade in mismatch repair deficient non-colorectal gastrointestinal cancers [abstract]. J Clin Oncol. 2016;34:Abstr nr 195.
54. Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, et al. KEYNOTE-059 cohort 1: efficacy and safety of pembrolizumab (pembro) monotherapy in patients with previously treated advanced gastric cancer [abstract]. J Clin Oncol. 2017;35:Abstr nr 4003.
55. Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, 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 https://doi.org/10.1016/S1470-2045(1017)30422-30429.
56. El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017;389:2492-502.
57. Kaufman HL, Russell J, Hamid O, Bhatia S, Terheyden P, D'Angelo SP, et al. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol. 2016;17:1374-85.
58. Khunger M, Hernandez AV, Pasupuleti V, Rakshit S, Pennell NA, Stevenson J, et al. Programmed cell death 1 (PD-1) ligand (PD-L1) expression in solid tumors as a predictive biomarker of benefit from PD-1/PD-L1 axis inhibitors: A systematic review and meta-analysis. JCO Precision Oncology. 2017 https://doi.org/10.1200/PO.1216.00030.
59. Hirsch FR, McElhinny A, Stanforth D, Ranger-Moore J, Jansson M, Kulangara K, et al. PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the blueprint PD-L1 IHC assay comparison project. J Thorac Oncol. 2017;12:208-22.
60. Dijkstra KK, Voabil P, Schumacher TN, Voest EE. Genomics- and transcriptomics-based patient selection for cancer treatment with immune checkpoint inhibitors: a review. JAMA Oncol. 2016;2:1490-5.
61. Gong J, Wang C, Lee PP, Chu P, Fakih M. Response to PD-1 blockade in microsatellite stable metastatic colorectal cancer harboring a POLE mutation. J Natl Compr Cancer Netw. 2017;15:142-7.
62. Zou W, Wolchok JD, Chen L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers, and combinations. Sci Transl Med. 2016;8:328rv324.
63. Gopalakrishnan V, Spencer C, Reuben A, Prieto P, Vicente D, Karpinets TV, et al. Response to anti-PD-1 based therapy in metastatic melanoma patients is associated with the diversity and composition of the gut microbiome [abstract]. Cancer Res. 2017;77:Abstr nr 2672.
64. Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350:1084-9.
65. Saleh K, Khalife-Saleh N and Kourie HR. Is gut microbiome a predictive marker to response to immune checkpoint inhibitors? Immunotherapy. 2017; 9: https://doi.org/10.2217/imt-2017-0090.
66. Mlecnik B, Bindea G, Angell HK, Maby P, Angelova M, Tougeron D, et al. Integrative analyses of colorectal cancer show immunoscore is a stronger predictor of patient survival than microsatellite instability. Immunity. 2016;44:698-711.
67. Abril-Rodriguez G, Ribas A. SnapShot: immune checkpoint inhibitors. Cancer Cell. 2017;31:848-848.e841.
68. Hugo W, Zaretsky JM, Sun L, Song C, Moreno BH, Hu-Lieskovan S, et al. Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell. 2016;165:35-44.
69. Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med. 2016;375:819-29.
70. Champiat S, Dercle L, Ammari S, Massard C, Hollebecque A, Postel-Vinay S, et al. Hyperprogressive disease is a new pattern of progression in cancer patients treated by anti-PD-1/PD-L1. Clin Cancer Res. 2017;23:1920-8.
71. Kato S, Goodman A, Walavalkar V, Barkauskas DA, Sharabi A, Kurzrock R. Hyperprogressors after immunotherapy: analysis of genomic alterations associated with accelerated growth rate. Clin Cancer Res. 2017;23:4242-50.
72. Nishijima TF, Shachar SS, Nyrop KA, Muss HB. Safety and tolerability of PD-1/PD-L1 inhibitors compared with chemotherapy in patients with advanced cancer: a meta-analysis. Oncologist. 2017;22:470-9.
73. AstraZeneca. Celgene and AstraZeneca provide update on the FUSION clinical trial programme. https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2017/celgene-and-astrazeneca-provide-update-on-the-fusion-clinical-trial-programme-07092017.html. Accessed 25 Sept 2017.
74. Bristol-Myers Squibb Press Release. Bristol-Myers Squibb provides an update on three Opdivo-based combination clinical studies in multiple myeloma. https://news.bms.com/press-release/corporatefinancial-news/bristol-myers-squibb-provides-update-three-opdivo-based-combin. Accessed 25 Sept 2017.
75. U.S. Food and Drug Administration. FDA alerts healthcare professionals and oncology clinical investigators about two clinical trials on hold evaluating KEYTRUDA® (pembrolizumab) in patients with multiple myeloma. https://www.fda.gov/Drugs/DrugSafety/ucm574305.htm. Accessed 25 Sept 2017.
76. Harmankaya K, Erasim C, Koelblinger C, Ibrahim R, Hoos A, Pehamberger H, et al. Continuous systemic corticosteroids do not affect the ongoing regression of metastatic melanoma for more than two years following ipilimumab therapy. Med Oncol. 2011;28:1140-4.
77. Horvat TZ, Adel NG, Dang TO, 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. J Clin Oncol. 2015;33:3193-8.
78. 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. 2017;35:785-92.
79. Friedman CF, Proverbs-Singh TA, Postow MA. Treatment of the immune-related adverse effects of immune checkpoint inhibitors: a review. JAMA Oncol. 2016;2:1346-53.
80. Haanen JBAG, Carbonnel F, Robert C, Kerr KM, Peters S, Larkin J, et al. Management of toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28:iv119-42.
81. Blumenthal GM, Theoret MR and Pazdur R. Treatment beyond progression with immune checkpoint inhibitors-known unknowns. JAMA Oncol. 2017 https://doi.org/10.1001/jamaoncol.2017.
82. Escudier B, Motzer RJ, Sharma P, Wagstaff J, Plimack ER, Hammers HJ, et al. Treatment beyond progression in patients with advanced renal cell carcinoma treated with nivolumab in CheckMate 025. Eur Urol. 2017;72:368-76.
83. George S, Motzer RJ, Hammers HJ, Redman BG, Kuzel TM, Tykodi SS, et al. Safety and efficacy of nivolumab in patients with metastatic renal cell carcinoma treated beyond progression: a subgroup analysis of a randomized clinical trial. JAMA Oncol. 2016;2:1179-86.
84. Kazandjian D, Keegan P, Suzman DL, Pazdur R, Blumenthal GM. Characterization of outcomes in patients with metastatic non-small cell lung cancer treated with programmed cell death protein 1 inhibitors past RECIST version 1.1-defined disease progression in clinical trials. Semin Oncol. 2017;44:3-7.
85. Long GV, Weber JS, Larkin J, Atkinson V, Grob JJ, Schadendorf D, et al. Nivolumab for patients with advanced melanoma treated beyond progression: Analysis of 2 phase 3 clinical trials. JAMA Oncol. 2017 https://doi.org/10.1001/jamaoncol.2017.1588.
86. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228-47.
87. Seymour L, Bogaerts J, Perrone A, Ford R, Schwartz LH, Mandrekar S, et al. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol. 2017;18:e143-52.
88. Martini DJ, Lalani AA, Bossé D, Steinharter JA, Harshman LC, Hodi FS, et al. Response to single agent PD-1 inhibitor after progression on previous PD-1/PD-L1 inhibitors: a case series. J Immunother Cancer. 2017;5:66.
89. Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M, et al. First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. N Engl J Med. 2017;376:2415-26.
90. Cohen EE, Harrington KJ, Le Tourneau C, Dinis J, Licitra L, Ahn MJ, et al. Pembrolizumab (pembro) vs standard of care (SOC) for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC): phase 3 KEYNOTE-040 trial [abstract]. Ann Oncol. 2017;28:Abstr nr LBA45.
91. Roche. Roche provides update on phase III study of TECENTRIQ® (atezolizumab) in people with previously treated advanced bladder cancer. https://www.roche.com/dam/jcr:8fa0d3ca-f68d-413c-a8fa-cb94514492e6/en/med-cor-2017-05-10-e.pdf. Accessed 25 Sept 2017.
92. Duran I. Second-line treatment of urothelial cancer: Achievements and perspectives [oral presentation]. ESMO 2017 Congress. 2017: Madrid, Spain. 8 Sept 2017. https://cslide.ctimeetingtech.com/library/esmo/browse/search/2dMo#2Hnb.
93. Remon J, Besse B, Soria JC. Successes and failures: what did we learn from recent first-line treatment immunotherapy trials in non-small cell lung cancer? BMC Med. 2017;15:55.
94. Su Z and Zhu M. Is it time for the weighted log-rank test to play a more important role in confirmatory trials? Contemp Clin Trials Comm. 2017 https://doi.org/10.1016/j.conctc.2017.1009.1007.