Beyond melanoma: Inhibiting the PD-1/PD-L1 pathway in solid tumors

Immunotherapy

Volumn 8, Issue 5, 2016, Pages 583-600

  Gentzler, Ryan ^a   Hall, Richard ^a   Kunk, Paul R ^a   Gaughan, Elizabeth ^a   Dillon, Patrick ^a   Slingluff, Craig L ^a   Rahma, Osama E ^a  

^a UNIVERSITY OF VIRGINIA HEALTH SYSTEM   (United States)

Author keywords

atezolizumab; immune checkpoint blockage; immune checkpoint inhibitors; immunotherapy; nivolumab; PD 1; PD L1; pembrolizumab; solid tumors; tumor infiltrating lymphocytes

Indexed keywords

ATEZOLIZUMAB; AVELUMAB; DURVALUMAB; NIVOLUMAB; PEMBROLIZUMAB; PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH 1 RECEPTOR; TICILIMUMAB; ANTINEOPLASTIC AGENT; PDCD1 PROTEIN, HUMAN;

ANUS CANCER; BILE DUCT CARCINOMA; BREAST CANCER; CANCER COMBINATION CHEMOTHERAPY; CANCER IMMUNOTHERAPY; COLORECTAL CANCER; DIGESTIVE SYSTEM CANCER; GASTROESOPHAGEAL JUNCTION; GLIOBLASTOMA; HEAD AND NECK CANCER; HUMAN; IMMUNOMODULATION; KIDNEY CANCER; KIDNEY CARCINOMA; LIVER CELL CARCINOMA; LUNG CANCER; MELANOMA; MICROENVIRONMENT; MULTICENTER STUDY (TOPIC); NEOPLASM; NON SMALL CELL LUNG CANCER; NONHUMAN; PANCREAS CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROSTATE CANCER; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SMALL CELL LUNG CANCER; SOLID TUMOR; SQUAMOUS CELL CARCINOMA; STOMACH CANCER; TRANSITIONAL CELL CARCINOMA; ANIMAL; ANTAGONISTS AND INHIBITORS; IMMUNOLOGY; IMMUNOTHERAPY; MOLECULARLY TARGETED THERAPY; NEOPLASMS; PROCEDURES; SIGNAL TRANSDUCTION; SKIN NEOPLASMS; TUMOR MICROENVIRONMENT;

ANIMALS; ANTIGENS, CD274; ANTINEOPLASTIC AGENTS; HUMANS; IMMUNOTHERAPY; MELANOMA; MOLECULAR TARGETED THERAPY; NEOPLASMS; PROGRAMMED CELL DEATH 1 RECEPTOR; SIGNAL TRANSDUCTION; SKIN NEOPLASMS; TUMOR MICROENVIRONMENT;

EID: 84968867054     PISSN: 1750743X     EISSN: 17507448     Source Type: Journal    
DOI: 10.2217/imt-2015-0029     Document Type: Review

References (105)

1. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science 331(6024), 1565-1570 (2011).
2. Hodi FS, O'Day SJ, McDermott DF et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363(8), 711-723 (2010).
3. Robert C, Schachter J, Long GV et al. Pembrolizumab versus ipilimumab in advanced melanoma. N. Engl. J. Med. 372(26), 2521-2532 (2015).
4. Robert C, Long GV, Brady B et al. Nivolumab in previously untreated melanoma without BRAF mutation. N. Engl. J. Med. 372(4), 320-330 (2015).
5. Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu. Rev. Immunol. 23, 515-548 (2005).
6. Carter L, Fouser LA, Jussif J et al. PD-1:PD-L inhibitory pathway affects both CD4(+) and CD8(+) T cells and is overcome by IL-2. Eur. J. Immunol. 32(3), 634-643 (2002).
7. Dong H, Strome SE, Salomao DR et al. Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion. Nat. Med. 8(8), 793-800 (2002).
8. Taube JM, Anders RA, Young GD et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci. Transl. Med. 4(127), 127ra137 (2012).
9. Teng MW, Ngiow SF, Ribas A, Smyth MJ. Classifying Cancers Based on T-cell Infiltration and PD-L1. Cancer Res. 75(11), 2139-2145 (2015).
10. Nakanishi J, Wada Y, Matsumoto K, Azuma M, Kikuchi K, Ueda S. Overexpression of B7-H1 (PD-L1) significantly associates with tumor grade and postoperative prognosis in human urothelial cancers. Cancer Immunol Immunother. 56(8), 1173-1182 (2007).
11. 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. 28(3), 682-688 (2011).
12. Nomi T, Sho M, Akahori T et al. Clinical significance and therapeutic potential of the programmed death-1 ligand/ programmed death-1 pathway in human pancreatic cancer. Clin. Cancer Res. 13(7), 2151-2157 (2007).
13. Rozali EN, Hato SV, Robinson BW, Lake RA, Lesterhuis WJ. Programmed death ligand 2 in cancer-induced immune suppression. Clin. Dev. Immunol. 2012, 656340 (2012).
14. Rosenwald A, Wright G, Leroy K et al. Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J. Exp. Med. 198(6), 851-862 (2003).
15. Lyford-Pike S, Peng S, Young GD et al. Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPVassociated head and neck squamous cell carcinoma. Cancer Res. 73(6), 1733-1741 (2013).
16. Chow LQ, Burtness B, Weiss J et al. A Phase Ib study of pembrolizumab in patients with human papilloma virus (HPV)-positive and negative head and neck cancer. Presented at: European Society for Medical Oncology (ESMO) 2014 Congress. Madrid, Spain, 26-30 September 2014.
17. Seiwert TY, Haddad RI, Gupta S et al. Antitumor activity and safety of pembrolizumab in patients (pts) with advanced squamous cell carcinoma of the head and neck (SCCHN): Preliminary results from KEYNOTE-012 expansion cohort. Presented at: ASCO Annual Meeting 2015. Chicago, IL, USA. 29 May-2 June 2015.
18. Segal NH, Antonia SJ, Brahmer JR et al. Preliminary data from a multi-arm expansion study of MEDI4736, an anti-PD-L1 antibody. Presented at: American Society of Clinical Oncology (ASCO) Annual Meeting 2014. Chicago, IL, USA 30 May-3 June 2014.
19. Berghoff AS, Kiesel B, Widhalm G et al. PD1 and PD-L1 expression in glioblastoma. Presented at: American Society of Clinical Oncology (ASCO) Annual Meeting 2014. Chicago, IL, USA, 30 May-3 June 2014.
20. Sampson JH, Vlahovic G, Sahebjam S et al. Preliminary safety and activity of nivolumab and its combination with ipilimumab in recurrent glioblastoma (GBM): CHECKMATE-143. Presented at: ASCO Annual Meeting 2015. Chicago, IL, USA, 29 May-2 June 2015.
21. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 507(7492), 315-322 (2014).
22. Bellmunt JP, Powles DP, Braiteh T et al. Inhinition of PD-L1 by MPDL3280A leads to clinical activity in pts with metastatic urothelial bladder cancer (UBC). Presented at: American Society of Clinical Oncology (ASCO) Annual Meeting 2014. Chicago, IL, USA, 30 May-3 June 2014.
23. Petrylak DP, Powles T, Bellmunt J et al. A Phase Ia study of MPDL3280A (anti-PDL1): Updated response and survival data in urothelial bladder cancer (UBC). Presented at: ASCO Annual Meeting 2015. Chicago, IL, USA, 29 May-2 June 2015.
24. Bellmunt J, Berger R, Montgomery B et al. Phase 1b study of pembrolizumab (Pembro; MK-3475) in patients (pts) with advanced urothelial tract cancer. Presented at: American Society of Clinical Oncology (ASCO) Annual Meeting 2014. Chicago, IL, USA, 30 May-3 June 2014.
25. Leite KR, Reis ST, Junior JP et al. PD-L1 expression in renal cell carcinoma clear cell type is related to unfavorable prognosis. Diagn. Pathol. 10, 189 (2015).
26. Thompson RH, Dong H, Kwon ED. Implications of B7-H1 expression in clear cell carcinoma of the kidney for prognostication and therapy. Clin. Cancer Res. 13(2 Pt 2), s709-s715 (2007).
27. Shin SJ, Jeon YK, Kim PJ et al. Clinicopathologic analysis of PD-L1 and PD-L2 expression in renal cell carcinoma: Association with oncogenic proteins status. Ann. Surg. Oncol. (2015) (Epub ahead of print).
28. Joseph RW, Millis SZ, Carballido EM et al. PD-1 and PD-L1 expression in renal cell carcinoma with sarcomatoid differentiation. Cancer Immunol. Res, 3(12), 1303-1307 (2015).
29. Topalian SL, Hodi FS, Brahmer JR et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366(26), 2443-2454 (2012).
30. Motzer RJ, Rini BI, McDermott DF et al. Nivolumab for metastatic renal cell carcinoma: results of a randomized Phase II trial. J. Clin. Oncol. 33(13), 1430-1437 (2015).
31. Motzer RJ, Escudier B, McDermott DF et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N. Engl. J. Med. 373(19), 1803-1813 (2015).
32. 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. 366(26), 2455-2465 (2012).
33. Hammers HJ, Plimack ER, Infante JR et al. Phase I study of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma (mRCC). Presented at: American Society of Clinical Oncology (ASCO) Annual Meeting 2014. Chicago, IL, USA, 30 May-3 June 2014.
34. Kantoff PW, Higano CS, Shore ND et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N. Engl. J. Med. 363(5), 411-422 (2010).
35. Slovin SF, Higano CS, Hamid O et al. Ipilimumab alone or in combination with radiotherapy in metastatic castrationresistant prostate cancer: results from an open-label, multicenter Phase I/II study. Ann. Oncol. 24(7), 1813-1821 (2013).
36. Kwon ED, Drake CG, Scher HI 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, double-blind, Phase 3 trial. Lancet Oncol. 15(7), 700-712 (2014).
37. Galon J, Fridman WH, Pages F. The adaptive immunologic microenvironment in colorectal cancer: A novel perspective. Cancer Res. 67(5), 1883-1886 (2007).
38. Pages F, Kirilovsky A, Mlecnik B et al. In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer. J. Clin. Oncol. 27(35), 5944-5951 (2009).
39. Galon J, Costes A, Sanchez-Cabo F et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313(5795), 1960-1964 (2006).
40. Galon J, Pages F, Marincola FM et al. Cancer classification using the Immunoscore: A worldwide task force. J. Translat. Med. 10, 205 (2012).
41. Galon J, Mlecnik B, Bindea G et al. Toward the introduction of the 'Immunoscore' in the classification of malignant tumours. J. Pathol. 232(2), 199-209 (2014).
42. Nagorsen D, Keilholz U, Rivoltini L et al. Natural T-cell response against MHC class I epitopes of epithelial cell adhesion molecule, her-2/neu, and carcinoembryonic antigen in patients with colorectal cancer. Cancer Res. 60(17), 4850-4854 (2000).
43. Droeser RA, Hirt C, Viehl CT et al. Clinical impact of programmed cell death ligand 1 expression in colorectal cancer. Eur. J. Cancer 49(9), 2233-2242 (2013).
44. 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. 19(2), 462-468 (2013).
45. Le DT, Uram JN, Wang H et al. PD-1 blockade in tumors with mismatch-repair deficiency. N. Engl. J. Med. 372(26), 2509-2520 (2015).
46. Shinto E, Hase K, Hashiguchi Y et al. CD8+ and FOXP3+ tumor-infiltrating T cells before and after chemoradiotherapy for rectal cancer. Ann. Surg. Oncol. 21(Suppl. 3), S414-S421 (2014).
47. Ott PA, Piha-Paul SA, Munster P et al. Pembrolizumab (MK-3475) for PD-L1-positive squamous cell carcinoma (SCC) of the anal canal: Preliminary safety and efficacy results from KEYNOTE-028. Presented at: The European Cancer Congress (ECC 2015). Vienna, Austria, 25-29 September 2015
48. Protti MP, De Monte L. Immune infiltrates as predictive markers of survival in pancreatic cancer patients. Front. Physiol. 4, 210 (2013).
49. Ino Y, Yamazaki-Itoh R, Shimada K et al. Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer. Br. J. Cancer 108(4), 914-923 (2013).
50. Feig C, Gopinathan A, Neesse A, Chan DS, Cook N, Tuveson DA. The pancreas cancer microenvironment. Clin. Cancer Res. 18(16), 4266-4276 (2012).
51. Loos M, Hedderich DM, Ottenhausen M et al. Expression of the costimulatory molecule B7-H3 is associated with prolonged survival in human pancreatic cancer. BMC cancer 9, 463 (2009).
52. Goeppert B, Frauenschuh L, Zucknick M et al. Prognostic impact of tumour-infiltrating immune cells on biliary tract cancer. Br. J. Cancer 109(10), 2665-2674 (2013).
53. Tran E, Turcotte S, Gros A et al. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science 344(6184), 641-645 (2014).
54. Ye Y, Zhou L, Xie X, Jiang G, Xie H, Zheng S. Interaction of B7-H1 on intrahepatic cholangiocarcinoma cells with PD-1 on tumor-infiltrating T cells as a mechanism of immune evasion. J. Surg. Oncol. 100(6), 500-504 (2009).
55. Fu J, Xu D, Liu Z et al. Increased regulatory T cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients. Gastroenterology 132(7), 2328-2339 (2007).
56. Gao Q, Qiu SJ, Fan J et al. Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection. J. Clin. Oncol. 25(18), 2586-2593 (2007).
57. Hoechst B, Voigtlaender T, Ormandy L et al. Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor. Hepatology 50(3), 799-807 (2009).
58. Gao Q, Wang XY, Qiu SJ et al. Overexpression of PDL1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin. Cancer Res. 15(3), 971-979 (2009).
59. El-Khoueiry ABMI, Crocenzi TS, Hobart WT et al. Phase I/ II safety and antitumor activity of nivolumab in patients with advanced hepatocellular carcinoma (HCC): CA209-040. Presented at: ASCO Annual Meeting 2015. Chicago, IL, USA 29 May-2 June 2015.
60. Saito H, Kuroda H, Matsunaga T, Osaki T, Ikeguchi M. Increased PD-1 expression on CD4+ and CD8+ T cells is involved in immune evasion in gastric cancer. J. Surg. Oncol. 107(5), 517-522 (2013).
61. Lu B, Chen L, Liu L et al. T-cell-mediated tumor immune surveillance and expression of B7 co-inhibitory molecules in cancers of the upper gastrointestinal tract. Immunol. Res. 50(2-3), 269-275 (2011).
62. Zheng Z, Bu Z, Liu X et al. Level of circulating PD-L1 expression in patients with advanced gastric cancer and its clinical implications. Chin. J. Cancer Res. 26(1), 104-111 (2014).
63. Eto S, Yoshikawa K, Nishi M et al. Programmed cell death protein 1 expression is an independent prognostic factor in gastric cancer after curative resection. Gastric Cancer (2015) (Epub ahead of print).
64. Ohigashi Y, Sho M, Yamada Y et al. Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin. Cancer Res. 11(8), 2947-2953 (2005).
65. Eto S, Iwata T, Yoshikawa K et al. Relationship of programmed death 1 (PD-1) expression to the recurrence in gastric cancer. Presented at: 2015 Gastrointestinal Cancers Symposium (ASCO GI). San Francisco, CA, 15-17 January 2015.
66. Muro K, Bang Y-J, Shankaran V et al. Relationship between PD-L1 expression and clinical outcomes in patients (Pts) with advanced gastric cancer treated with the anti-PD-1 monoclonal antibody pembrolizumab (Pembro; MK-3475) in KEYNOTE-012. Presented at: 2015 Gastrointestinal Cancers Symposium (ASCO GI). San Francisco, CA, 15-17 January 2015.
67. Shankaran V, Muro K, Bang Y-J et al. Correlation of gene expression signatures and clinical outcomes in patients with advanced gastric cancer treated with pembrolizumab (MK-3475). Presented at: 2015 Gastrointestinal Cancers Symposium (ASCO GI). San Francisco, CA, 15-17 January 2015.
68. Herbst RS, Soria JC, Kowanetz M et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 515(7528), 563-567 (2014).
69. Dieci MV, Criscitiello C, Goubar A et al. Prognostic value of tumor-infiltrating lymphocytes on residual disease after primary chemotherapy for triple-negative breast cancer: A retrospective multicenter study. Ann. Oncol. 25(3), 611-618 (2014).
70. Ono M, Tsuda H, Shimizu C et al. Tumor-infiltrating lymphocytes are correlated with response to neoadjuvant chemotherapy in triple-negative breast cancer. Breast Cancer Res Treat. 132(3), 793-805 (2012).
71. Ali HR, Provenzano E, Dawson SJ et al. Association between CD8+ T-cell infiltration and breast cancer survival in 12, 439 patients. Ann. Oncol. 25(8), 1536-1543 (2014).
72. Denkert C, Loibl S, Noske A et al. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J. Clin. Oncol. 28(1), 105-113 (2010).
73. Loi S. Tumor-infiltrating lymphocytes, breast cancer subtypes and therapeutic efficacy. Oncoimmunology 2(7), e24720 (2013).
74. Dushyanthen S, Beavis PA, Savas P et al. Relevance of tumorinfiltrating lymphocytes in breast cancer. BMC Med. 13, 202 (2015).
75. Muenst S, Soysal SD, Gao F, Obermann EC, Oertli D, Gillanders WE. The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat. 139(3), 667-676 (2013).
76. Stagg J, Loi S, Divisekera U et al. Anti-ErbB-2 mAb therapy requires type I and II interferons and synergizes with anti-PD-1 or anti-CD137 mAb therapy. Proc. Natl Acad. Sci. USA 108(17), 7142-7147 (2011).
77. Gatalica Z, Snyder C, Maney T et al. Programmed cell death 1 (PD-1) and its ligand (PD-L1) in common cancers and their correlation with molecular cancer type. Cancer Epidemiol. Biomarkers Prev. 23(12), 2965-2970 (2014).
78. Mittendorf EA, Philips AV, Meric-Bernstam F et al. PD-L1 expression in triple-negative breast cancer. Cancer Immunol. Res. 2(4), 361-370 (2014).
79. Barrett MT, Anderson KS, Lenkiewicz E et al. Genomic amplification of 9p24. 1 targeting JAK2, PD-L1, and PDL2 is enriched in high-risk triple negative breast cancer. Oncotarget 6(28), 26483-26493 (2015).
80. Nanda RC, Laura Q, Dees EC, Berger R et al. A Phase Ib study of pembrolizumab (MK-3475) in patients with advanced triple-negative breast cancer. Presented at: Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium. San Antonio, TX, 9-13 December 2014.
81. Emens LAB, Fadi S Cassier, Philippe DeLord et al. Inhibition of PD-L1 by MPDL3280A leads to clinical activity in patients with metastatic triple-negative breast cancer. Presented at: Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium. San Antonio, TX, 9-13 December 2014.
82. Gettinger SN, Horn L, Gandhi L et al. Overall survival and long-term safety of nivolumab (anti-programmed death 1 antibody, BMS-936558, ONO-4538) in patients with previously treated advanced non-small-cell lung cancer. J. Clin. Oncol. 33(18), 2004-2012 (2015).
83. Garon EB, Rizvi NA, Hui R et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N. Engl. J. Med. 372(21), 2018-2028 (2015).
84. Rizvi NA, Mazieres J, Planchard D et al. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-smallcell lung cancer (CheckMate 063): A Phase 2, single-arm trial. Lancet Oncol. 16(3), 257-265 (2015).
85. Brahmer J, Reckamp KL, Baas P et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N. Engl. J. Med. 373(2), 123-135 (2015).
86. Borghaei H, Paz-Ares L, Horn L et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N. Engl. J. Med. 373(17), 1627-1639 (2015).
87. Herbst RS, Baas P, Kim DW et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): A randomised controlled trial. Lancet doi:10. 1016/S0140-6736(15)01281-7 (2015) (Epub ahead of print).
88. Horn L, Spigel DR, Gettinger SN et al. Clinical activity, safety and predictive biomarkers of the engineered antibody MPDL3280A (anti-PDL1) in non-small cell lung cancer (NSCLC): update from a Phase Ia study. ASCO Meeting Abstracts 33(Suppl. 15), 8029 (2015).
89. Spira AI, Park K, Mazieres J et al. Efficacy, safety and predictive biomarker results from a randomized Phase II study comparing MPDL3280A vs docetaxel in 2L/3L NSCLC (POPLAR). ASCO Meeting Abstracts 33(Suppl. 15), 8010 (2015).
90. Rizvi NA, Brahmer JR, Ou S-HI et al. Safety and clinical activity of MEDI4736, an anti-programmed cell deathligand 1 (PD-L1) antibody, in patients with non-small cell lung cancer (NSCLC). ASCO Meeting Abstracts 33(Suppl. 15), 8032 (2015).
91. Gulley JL, Spigel D, Kelly K et al. Avelumab (MSB0010718C), an anti-PD-L1 antibody, in advanced NSCLC patients: A phase 1b, open-label expansion trial in patients progressing after platinum-based chemotherapy. ASCO Meeting Abstracts 33(Suppl. 15), 8034 (2015).
92. Rizvi NA, Antonia SJ, Chow LQM et al. A Phase I study of nivolumab (anti-PD-1; BMS-936558, ONO-4538) plus platinum-based doublet chemotherapy (PT-doublet) in chemotherapy-naive non-small cell lung cancer (NSCLC) patients (pts). ASCO Meeting Abstracts 31(Suppl. 15), 8072 (2013).
93. Antonia SJ, Brahmer JR, Gettinger S et al. Nivolumab (anti-PD-1; BMS-936558, ONO-4538) in combination with platinum-based doublet chemotherapy (PT-DC) in advanced non-small cell lung cancer (NSCLC). Int. J. Radiat. Oncol. Biol. Phys. 90(5), S2 (2014).
94. Gettinger SN, Hellmann MD, Shepherd FA et al. First-line monotherapy with nivolumab (NIVO; anti-programmed death-1 [PD-1]) in advanced non-small cell lung cancer (NSCLC): Safety, efficacy and correlation of outcomes with PD-1 ligand (PD-L1) expression. ASCO Meeting Abstracts 33(Suppl. 15), 8025 (2015).
95. Papadimitrakopoulou V, Patnaik A, Borghaei H et al. Pembrolizumab (pembro; MK-3475) plus platinum doublet chemotherapy (PDC) as front-line therapy for advanced nonsmall cell lung cancer (NSCLC): KEYNOTE-021 Cohorts A and C. ASCO Meeting Abstracts 33(Suppl. 15), 8031 (2015).
96. Antonia SJ, Gettinger S, Goldman J et al. Safety and efficacy of first-line nivolumab (Anti-PD-1; BMS-936558, ONO-4538) and ipilimumab in non-small cell lung cancer (NSCLC). Int. J. Radiat. Oncol. Biol. Phys. 90(5), S32-S33 (2014).
97. Antonia SJ, Bendell JC, Taylor MH et al. Phase I/II study of nivolumab with or without ipilimumab for treatment of recurrent small cell lung cancer (SCLC): CA209-032. ASCO Meeting Abstracts 33(Suppl. 15), 7503 (2015).
98. Patnaik A, Socinski MA, Gubens MA et al. Phase 1 study of pembrolizumab (pembro; MK-3475) plus ipilimumab (IPI) as second-line therapy for advanced non-small cell lung cancer (NSCLC): KEYNOTE-021 cohort D. ASCO Meeting Abstracts 33(Suppl. 15), 8011 (2015).
99. Antonia SJ, Goldberg SB, Balmanoukian AS et al. Phase Ib study of MEDI4736, a programmed cell death ligand-1 (PD-L1) antibody, in combination with tremelimumab, a cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) antibody, in patients (pts) with advanced NSCLC. ASCO Meeting Abstracts 33(Suppl. 15), 3014 (2015).
100. Liu SV, Powderly JD, Camidge DR et al. Safety and efficacy of MPDL3280A (anti-PDL1) in combination with platinumbased doublet chemotherapy in patients with advanced nonsmall cell lung cancer (NSCLC). ASCO Meeting Abstracts 33(Suppl. 15), 8030 (2015).
101. Nghiem P, Bhatia S, Daud A et al. Activity of PD-1 blockade with pembrolizumab as first systemic therapy in patients with advanced Merkel cell carcinoma. Presented at: The European Cancer Congress (ECC 2015). Vienna, Austria, 25-29 September 2015.
102. Hubbard-Lucey VM, Tontonoz MJ. Translating science into survival: Report on the Inaugural International Cancer Immunotherapy Conference. Cancer Immunol. Res. 4, 3-11 (2016).
103. Larkin J, Chiarion-Sileni V, Gonzalez R et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N. Engl. J. Med. 373(1), 23-34 (2015).
104. Tumeh PC, Harview CL, Yearley JH et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515(7528), 568-571 (2014).
105. Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science 348(6230), 69-74 (2015).