108
Views
2
CrossRef citations to date
0
Altmetric
Review

PD-1 and PD-L1 as emerging therapeutic targets in gastric cancer: current evidence

, , &
Pages 1-11 | Published online: 05 May 2017

References

  • Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.
  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29.
  • Bang Y-J, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–697.
  • Wilke H, Muro K, Van Cutsem E, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15(11):1224–1235.
  • Fuchs CS, Tomasek J, Yong CJ, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383(9911):31–39.
  • Yang W, Raufi A, Klempner SJ. Targeted therapy for gastric cancer: molecular pathways and ongoing investigations. Biochim Biophys Acta. 2014;1846(1):232–237.
  • Raufi AG, Klempner SJ. Immunotherapy for advanced gastric and esophageal cancer: preclinical rationale and ongoing clinical investigations. J Gastrointest Oncol. 2015;6(5):561.
  • Chow LQ, Haddad R, Gupta S, et al. Antitumor activity of pembrolizumab in biomarker-unselected patients with recurrent and/or metastatic head and neck squamous cell carcinoma: results from the phase Ib KEYNOTE-012 expansion cohort. J Clin Oncol. 2016;34(32):3838–3845.
  • Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015;372(4):311–319.
  • Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1803–1813.
  • Rosenberg JE, Hoffman-Censits J, Powles T, 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(10031):1909–1920.
  • Fehrenbacher L, Spira A, Ballinger M, 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(10030):1837–1846.
  • Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627–1639.
  • Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373(2):123–135.
  • Herbst RS, Baas P, Kim D-W, 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(10027):1540–1550.
  • Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–2028.
  • Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;2015(373):23–34.
  • Ribas A, Puzanov I, Dummer R, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015;16(8):908–918.
  • Rooney MS, Shukla SA, Wu CJ, Getz G, Hacohen N. Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell. 2015;160(1–2):48–61.
  • Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1–10.
  • Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509–2520.
  • Kaneda MM, Messer KS, Ralainirina N, et al. PI3Kγ is a molecular switch that controls immune suppression. Nature. 2016;539(7629):437–442.
  • Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202–209.
  • Cancer Genome Atlas Research Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487(7407):330–337.
  • Böger C, Behrens H-M, Mathiak M, Krüger S, Kalthoff H, Röcken C. PD-L1 is an independent prognostic predictor in gastric cancer of Western patients. Oncotarget. 2016;7(17):24269–24283.
  • Bernal M, Concha A, Sáenz-López P, et al. Leukocyte infiltrate in gastrointestinal adenocarcinomas is strongly associated with tumor microsatellite instability but not with tumor immunogenicity. Cancer Immunol Immunother. 2011;60(6):869–882.
  • Spranger S, Gajewski TF. Tumor-intrinsic oncogene pathways mediating immune avoidance. Oncoimmunology. 2016;5(3):e1086862.
  • Gajewski TF. The next hurdle in cancer immunotherapy: overcoming the non-T-cell-inflamed tumor microenvironment. Semin Oncol. 2015;42(4):663–671.
  • Hu-Lieskovan S, Ribas A. New combination strategies using programmed cell death 1/programmed cell death ligand 1 checkpoint inhibitors as a backbone. Cancer J. 2017;23(1):10–22.
  • Blank CU, Haanen JB, Ribas A, Schumacher TN. Cancer immunology. The “cancer immunogram”. Science. 2016;352(6286):658–660.
  • Spranger S, Bao R, Gajewski TF. Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature. 2015;523(7559):231–235.
  • Lin SJ, Gagnon-Bartsch JA, Tan IB, et al. Signatures of tumour immunity distinguish Asian and non-Asian gastric adenocarcinomas. Gut. 2015;64(11):1721–1731.
  • Rizvi NA, Hellmann MD, Snyder A, et al. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124–128.
  • Ribic CM, Sargent DJ, Moore MJ, et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med. 2003;349(3):247–257.
  • Lesokhin AM, Callahan MK, Postow MA, Wolchok JD. On being less tolerant: enhanced cancer immunosurveillance enabled by targeting checkpoints and agonists of T cell activation. Sci Transl Med. 2015;7(280):280sr1.
  • Rosenberg JE, Hoffman-Censits J, Powles T, 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(10031):1909–1920.
  • Balar AV, Galsky MD, Rosenberg JE, 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(10064):67–76.
  • McGranahan N, Furness AJ, Rosenthal R, et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science. 2016;351(6280):1463–1469.
  • Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823–1833.
  • Cho J, Lee J, Bang H, et al. Programmed cell death-ligand 1 expression predicts survival in patients with gastric carcinoma with microsatellite instability. Oncotarget. 2017;8(8):13320–13328.
  • Kim JW, Nam KH, Ahn SH, et al. Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer. Gastric Cancer. 2016;19(1):42–52.
  • Wu C, Zhu Y, Jiang J, Zhao J, Zhang X-G, Xu N. Immunohistochemical localization of programmed death-1 ligand-1 (PD-L1) in gastric carcinoma and its clinical significance. Acta Histochem. 2006;108(1):19–24.
  • Muro K, Chung HC, Shankaran V, et al. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial. Lancet Oncol. 2016;17(6):717–726.
  • Gaule P, Smithy JW, Toki M, et al. A quantitative comparison of antibodies to programmed cell death 1 ligand 1. JAMA Oncol. Epub 2016 Aug 18.
  • Scheel AH, Dietel M, Heukamp LC, et al. Harmonized PD-L1 immunohistochemistry for pulmonary squamous-cell and adenocarcinomas. Mod Pathol. 2016;29(10):1165–1172.
  • Sun J, Xu K, Wu C, et al. PD-L1 expression analysis in gastric carcinoma tissue and blocking of tumor-associated PD-L1 signaling by two functional monoclonal antibodies. Tissue Antigens. 2007;69(1):19–27.
  • 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. 2016;19(2):466–471.
  • Schlößer HA, Drebber U, Kloth M, et al. Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma. Oncoimmunology. 2016;5(5):e1100789.
  • Xiaofang X, Li Z, Wang J, et al. Analysis of PDL1 expression and T cells infiltration in 1014 gastric cancer patients. J Clin Oncol. 2017;35(suppl 4S; abstract 50).
  • Tanaka H, Tamura T, Hiramatsu S, et al. Role of systemic immune-inflammatory index, tumor infiltrating neutrophils and PD-1+ T cells to predict the postoperative recurrence after S-1 adjuvant chemotherapy for gastric cancer: a retrospective study. J Clin Oncol. 2017;35(suppl 4S; abstract 74).
  • Jiang Y, Zhang Q, Hu Y, et al. ImmunoScore signature: a prognostic and predictive tool in gastric cancer. Ann Surg. Epub 2016 Dec 20.
  • Janjigian YY, Bendell J, Calvo E, et al. CheckMate-032: phase I/II, open-label study of safety and activity of nivolumab (nivo) alone or with ipilimumab (ipi) in advanced and metastatic (A/M) gastric cancer (GC). J Clin Oncol. 2016;34(15 Suppl):4010.
  • Janjigian YY, Adenis A, Aucoin J-S, et al. Checkmate 649: a randomized, multicenter, open-label, phase 3 study of nivolumab (Nivo) plus ipilimumab (Ipi) versus oxaliplatin plus fluoropyrimidine in patients (Pts) with previously untreated advanced or metastatic gastric (G) or gastroesophageal junction (GEJ) cancer. J Clin Oncol. 2017;35.
  • Kang Yoon-Koo, Satoh Taroh, Ryu Min-Hee, et al. Nivolumab (ONO-4538/BMS-936558) as salvage treatment after second or later-line chemotherapy for advanced gastric or gastro-esophageal junction cancer (AGC): a double-blinded, randomized, phase III trial. J Clin Oncol. 2017;35(suppl 4S; abstract 2).
  • Doi T, Piha-Paul SA, Jalal SI, et al. Updated results for the advanced esophageal carcinoma cohort of the phase Ib KEYNOTE-028 study of pembrolizumab (MK-3475). J Clin Oncol. 2016;34(suppl 4S; abstr 7).
  • Chung HC, Arkenau H-T, Wyrwicz L, et al. Avelumab (MSB0010718C; anti-PD-L1) in patients with advanced gastric or gastroesophageal junction cancer from JAVELIN solid tumor phase Ib trial: analysis of safety and clinical activity. J Clin Oncol. 2016;34(suppl; abstr 4009).
  • Segal NH, Antonia SJ, Brahmer JR, et al. Preliminary data from a multi-arm expansion study of MEDI4736, an anti-PD-L1 antibody. J Clin Oncol. 2014;32:5s.
  • Voron T, Marcheteau E, Pernot S, et al. Control of the immune response by pro-angiogenic factors. Front Oncol. 2014;4:70.
  • Reardon DA, De Groot JF, Colman H, et al. Safety of pembrolizumab in combination with bevacizumab in recurrent glioblastoma (rGBM). J Clin Oncol. 2016;34(suppl; abstr 2010).
  • Dudek AZ, Sica RA, Sidani A, et al. Phase Ib study of pembrolizumab in combination with bevacizumab for the treatment of metastatic renal cell carcinoma: Big Ten Cancer Research Consortium BTCRC-GU14-003. J Clin Oncol. 2016;34(suppl 2S; abstr 559).
  • Solmaz S, Johnstone PA, Forsyth PA, et al. Safety and antitumor activity of hypofractionated stereotactic irradiation (HFSRT) with pembrolizumab (Pembro) and bevacizumab (Bev) in patients (pts) with recurrent high grade gliomas: preliminary results from phase I study. J Clin Oncol. 2016;34(suppl; abstr 2041).
  • Langer CJ, Gadgeel SM, Borghaei H, 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(11):1497–1508.
  • Ian Chau JCB, Emiliano Calvo, Rafael Santana-Davila, et al. Interim safety and clinical activity in patients (pts) with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma from a multicohort phase 1 study of ramucirumab (R) plus pembrolizumab (P). J Clin Oncol. 2017;35(suppl 4S; abstract 102).
  • Emens LA, Middleton G. The interplay of immunotherapy and chemotherapy: harnessing potential synergies. Cancer Immunol Res. 2015;3(5):436–443.
  • Fuchs CS, Ohtsu A, Tabernero J, et al. Preliminary safety data from KEYNOTE-059: pembrolizumab plus 5-fluorouracil (5-FU) and cisplatin for first-line treatment of advanced gastric cancer. J Clin Oncol. 2016;34(suppl; abstr 4037).
  • Herbst RS, Bendell JC, Isambert N, et al. A phase 1 study of ramucirumab (R) plus pembrolizumab (P) in patients (pts) with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma, non-small cell lung cancer (NSCLC), or urothelial carcinoma (UC): phase 1a results. J Clin Oncol. 2016;34(suppl; abstr 3056).
  • Vanneman M, Dranoff G. Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer. 2012;12(4):237–251.
  • Catenacci DVT, Kim SS, Gold PJ, et al. A phase 1b/2, open label, dose-escalation study of margetuximab (M) in combination with pembrolizumab (P) in patients with relapsed/refractory advanced HER2+ gastroesophageal (GEJ) junction or gastric (G) cancer. J Clin Oncol. 2017;35(suppl 4S; abstract TPS219).
  • Vatner RE, Cooper BT, Vanpouille-Box C, Demaria S, Formenti SC. Combinations of immunotherapy and radiation in cancer therapy. Front Oncol. 2014;4:325.
  • Dovedi SJ, Adlard AL, Lipowska-Bhalla G, et al. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res. 2014;74(19):5458–5468.
  • Chao J, Chen Y-J, Frankel PH, et al. Combining pembrolizumab and palliative radiotherapy in gastroesophageal cancer to enhance anti-tumor T-cell response and augment the abscopal effect. J Clin Oncol. 2017;35(suppl 4S; abstract TPS220).
  • Ikoma N, Blum M, Chiang YJ, et al. Yield of staging laparoscopy and lavage cytology for radiologically occult peritoneal carcinomatosis of gastric cancer. Ann Surg Oncol. 2016;23(13):4332–4337.
  • Ralph C, Elkord E, Burt DJ, et al. Modulation of lymphocyte regulation for cancer therapy: a phase II trial of tremelimumab in advanced gastric and esophageal adenocarcinoma. Clin Cancer Res. 2010;16(5):1662–1672.