Review of the recent clinical trials for PD-1/PD-L1 based lung cancer immunotherapy

References

• (WHO) WHO. Global cancer observatory. Lung Cancer; 2020 [ cited 2021 May 10]. Available from: https://gco.iarc.fr/
   Google Scholar
• Araujo LH, Horn L, Merritt RE, et al. Cancer of the lung: non–small cell lung cancer and small cell lung cancer. Abeloff’s Clinical Oncology. 2020:1108–1158. e16. Elsevier.
   Google Scholar
• Vincent TD, DeVita J, and Lawrence T, et al. CANCER: principles and Practice of Oncology Primer of Molecular Biology in Cancer. Philadelphia, United States: WOLTERS KLUWER MEDICAL; 2020.
   Google Scholar
• Tian Y, Zhai X, Han A, et al. Potential immune escape mechanisms underlying the distinct clinical outcome of immune checkpoint blockades in small cell lung cancer. J Hematol Oncol. 2019 Jun 28;12(1):67.
   PubMedGoogle Scholar
• Doyle A, Martin WJ, Funa K, et al. Markedly decreased expression of class I histocompatibility antigens, protein, and mRNA in human small-cell lung cancer. J Exp Med. 1985 May 1;161(5):1135–1151.
   PubMed Web of Science ®Google Scholar
• He Y, Rozeboom L, Rivard CJ, et al. MHC class II expression in lung cancer. Lung Cancer. 2017 Oct;112:75–80.
   PubMed Web of Science ®Google Scholar
• Shibakura M, Niiya K, Kiguchi T, et al. Induction of IL-8 and monoclyte chemoattractant protein-1 by doxorubicin in human small cell lung carcinoma cells. Int J Cancer. 2003 Jan 20;103(3):380–386.
   PubMed Web of Science ®Google Scholar
• Wang L, Ma Q, Yao R, et al. Current status and development of anti-PD-1/PD-L1 immunotherapy for lung cancer. Int Immunopharmacol. 2020 Feb;79:106088.
   PubMed Web of Science ®Google Scholar
• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020 Jan;70(1):7–30.
   PubMed Web of Science ®Google Scholar
• Yang P, Allen MS, Aubry MC, et al. Clinical features of 5,628 primary lung cancer patients: experience at mayo clinic from 1997 to 2003. Chest. 2005 Jul;128(1):452–462.
   PubMed Web of Science ®Google Scholar
• Kreuter M, Vansteenkiste J, Fischer JR, et al. Three-year follow-up of a randomized phase II trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine (the TREAT study). J Thorac Oncol. 2016 Jan;11(1):85–93.
   PubMed Web of Science ®Google Scholar
• Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011 Mar 4;144(5):646–674.
   PubMed Web of Science ®Google Scholar
• 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 Oct 22;373(17):1627–1639.
   PubMed Web of Science ®Google Scholar
• 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 Jul 9;373(2):123–135.
   PubMed Web of Science ®Google Scholar
• Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015 May 21;372(21):2018–2028.
   PubMed Web of Science ®Google Scholar
• Rittmeyer A, Barlesi F, Waterkamp D, 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 Jan 21;389(10066):255–265.
   PubMed Web of Science ®Google Scholar
• 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 Aug;8(8):793–800.
   PubMed Web of Science ®Google Scholar
• Sanmamed MF, Pastor F, Rodriguez A, et al. Agonists of co-stimulation in cancer immunotherapy directed against CD137, OX40, GITR, CD27, CD28, and ICOS. Semin Oncol. 2015 Aug;42(4):640–655.
   PubMed Web of Science ®Google Scholar
• Komrokji RS, Wei S, Mailloux AW, et al. A phase II study to determine the safety and efficacy of the oral inhibitor of indoleamine 2,3-dioxygenase (IDO) enzyme INCB024360 in patients with myelodysplastic syndromes. Clin Lymphoma Myeloma Leuk. 2019 Mar;19(3):157–161.
   PubMed Web of Science ®Google Scholar
• Pollack MH, Betof A, Dearden H, et al. Safety of resuming anti-PD-1 in patients with immune-related adverse events (irAEs) during combined anti-CTLA-4 and anti-PD1 in metastatic melanoma. Ann Oncol. 2018 Jan 1;29(1):250–255.
   PubMed Web of Science ®Google Scholar
• Freeman GJ, Long AJ, Iwai Y, 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 Oct 2;192(7):1027–1034.
   PubMed Web of Science ®Google Scholar
• Latchman Y, Wood CR, Chernova T, et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol. 2001 Mar;2(3):261–268.
   PubMed Web of Science ®Google Scholar
• Liang SC, Latchman YE, Buhlmann JE, et al. Regulation of PD-1, PD-L1, and PD-L2 expression during normal and autoimmune responses. Eur J Immunol. 2003 Oct;33(10):2706–2716.
   PubMed Web of Science ®Google Scholar
• Zitvogel L, Kroemer G. Targeting PD-1/PD-L1 interactions for cancer immunotherapy. Oncoimmunology. 2012 Nov 1;1(8):1223–1225.
   PubMed Web of Science ®Google Scholar
• Yokosuka T, Takamatsu M, Kobayashi-Imanishi W, et al. Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2. J Exp Med. 2012 Jun 4;209(6):1201–1217.
   PubMed Web of Science ®Google Scholar
• Baecher-Allan C, Brown JA, Freeman GJ, et al. CD4+CD25+ regulatory cells from human peripheral blood express very high levels of CD25 ex vivo. Novartis Found Symp. 2003;252:67–88. discussion 88–91, 106–14.
   PubMedGoogle Scholar
• He J, Hu Y, Hu M, et al. Development of PD-1/PD-L1 pathway in tumor immune microenvironment and treatment for non-small cell lung cancer. Sci Rep. 2015 Aug 17;5(1):13110.
   PubMedGoogle Scholar
• Thompson RH, Gillett MD, Cheville JC, et al. Costimulatory B7-H1 in renal cell carcinoma patients: indicator of tumor aggressiveness and potential therapeutic target. Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17174–17179.
   PubMed Web of Science ®Google Scholar
• 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. 2012 Mar 28;4(127):127ra37.
   PubMed Web of Science ®Google Scholar
• Chang CH, Curtis JD, Maggi LB Jr., et al. Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell. 2013 Jun 6;153(6):1239–1251.
   PubMed Web of Science ®Google Scholar
• Peng M, Yin N, Chhangawala S, et al. Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism. Science. 2016 Oct 28;354(6311):481–484.
   PubMed Web of Science ®Google Scholar
• Gerriets VA, Kishton RJ, Nichols AG, et al. Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation. J Clin Invest. 2015 Jan;125(1):194–207.
   PubMed Web of Science ®Google Scholar
• 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 Nov 10;375(19):1823–1833.
   PubMed Web of Science ®Google Scholar
• Brahmer JR, Rodriguez-Abreu D, Robinson AG, et al. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1600–1609.
   PubMed Web of Science ®Google Scholar
• Reck M, Rodriguez-Abreu D, Robinson AG, et al. Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol. 2019 Mar 1;37(7):537–546.
   PubMed Web of Science ®Google Scholar
• Lopes G, Wu Y-L, Kudaba I, et al. Pembrolizumab (pembro) versus platinum-based chemotherapy (chemo) as first-line therapy for advanced/metastatic NSCLC with a PD-L1 tumor proportion score (TPS) ≥ 1%: open-label, phase 3 KEYNOTE-042 study. J clin oncol. 2018. 2018 06 20;36(18_suppl):LBA4–LBA4.
   Web of Science ®Google Scholar
• Mok TSK, Wu YL, Kudaba I, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019 May 4;393(10183):1819–1830.
   PubMed Web of Science ®Google Scholar
• Nosaki K, Saka H, Hosomi Y, et al. Safety and efficacy of pembrolizumab monotherapy in elderly patients with PD-L1-positive advanced non-small-cell lung cancer: pooled analysis from the KEYNOTE-010, KEYNOTE-024, and KEYNOTE-042 studies. Lung Cancer. 2019 Sep;135:188–195.
   PubMed Web of Science ®Google Scholar
• 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 Nov;17(11):1497–1508.
   PubMed Web of Science ®Google Scholar
• Gandhi L, Rodriguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018 May 31;378(22):2078–2092.
   PubMed Web of Science ®Google Scholar
• Carbone DP, Reck M, Paz-Ares L, et al. First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. N Engl J Med. 2017 Jun 22;376(25):2415–2426.
   PubMed Web of Science ®Google Scholar
• Hellmann MD, Rizvi NA, Goldman JW, et al. Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study. Lancet Oncol. 2017 Jan;18(1):31–41.
   PubMed Web of Science ®Google Scholar
• Ready N, Hellmann MD, Awad MM, et al. First-line nivolumab plus ipilimumab in advanced non-small-cell lung cancer (CheckMate 568): outcomes by programmed death ligand 1 and tumor mutational burden as biomarkers. J Clin Oncol. 2019 Apr 20;37(12):992–1000.
   PubMed Web of Science ®Google Scholar
• Hellmann MD, Ciuleanu TE, Pluzanski A, et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 2018 May 31;378(22):2093–2104.
   PubMed Web of Science ®Google Scholar
• Wei SC, Levine JH, Cogdill AP, et al. Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade. Cell. 2017 Sep 7;170(6):1120–1133 e17.
   PubMed Web of Science ®Google Scholar
• Paz-Ares L, Ciuleanu TE, Cobo M, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):198–211.
   PubMed Web of Science ®Google Scholar
• Garassino M, Rizvi N, Besse B, et al. OA03.02 atezolizumab as 1L therapy for advanced NSCLC in PD-L1–selected patients: updated ORR, PFS and OS data from the BIRCH study. J Thorac Oncol. 2017;12(1):S251–S252.
   Web of Science ®Google Scholar
• Peters S, Gettinger S, Johnson ML, et al. Phase II trial of atezolizumab as first-line or subsequent therapy for patients with programmed death-ligand 1-selected advanced non-small-cell lung cancer (BIRCH). J Clin Oncol. 2017 Aug 20;35(24):2781–2789.
   PubMed Web of Science ®Google Scholar
• West H, McCleod M, Hussein M, et al. Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019 Jul;20(7):924–937.
   PubMed Web of Science ®Google Scholar
• Jotte R, Cappuzzo F, Vynnychenko I, et al. Atezolizumab in combination with Carboplatin and nab-paclitaxel in advanced squamous NSCLC (IMpower131): results from a randomized phase III trial. J Thorac Oncol. 2020 Aug;15(8):1351–1360.
   PubMed Web of Science ®Google Scholar
• Papadimitrakopoulou V, Cobo M, Bordoni R, et al. OA05.07 IMpower132: PFS and safety results with 1L Atezolizumab + Carboplatin/Cisplatin + pemetrexed in stage IV non-squamous NSCLC. J Thorac Oncol. 2018;13(10):S332–S333.
   Web of Science ®Google Scholar
• Socinski MA, Jotte RM, Cappuzzo F, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018 Jun 14;378(24):2288–2301.
   PubMed Web of Science ®Google Scholar
• Lin SH, Lin Y, Yao L, et al. Phase II trial of concurrent atezolizumab with chemoradiation for unresectable NSCLC. J Thorac Oncol. 2020 Feb;15(2):248–257.
   PubMed Web of Science ®Google Scholar
• Rizvi NA, Cho BC, Reinmuth N, et al. Durvalumab with or without tremelimumab vs standard chemotherapy in first-line treatment of metastatic non-small cell lung cancer: the MYSTIC phase 3 randomized clinical trial. JAMA Oncol. 2020 May 1;6(5):661–674.
   PubMed Web of Science ®Google Scholar
• 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. 2016 Apr 9;387(10027):1540–1550.
   PubMed Web of Science ®Google Scholar
• US food and drug administration: KEYTRUDA (pembrolizumab) [prescribing information]. [ cited 2020 Dec 11]. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125514s004s006lbl.pdf
   Google Scholar
• Garon EB, Hellmann MD, Rizvi NA, et al. Five-year overall survival for patients with advanced nonSmall-cell lung cancer treated with pembrolizumab: results from the phase I KEYNOTE-001 study. J Clin Oncol. 2019 Oct 1;37(28):2518–2527.
   PubMed Web of Science ®Google Scholar
• Reck M, Taylor F, Penrod JR, et al. Impact of nivolumab versus docetaxel on health-related quality of life and symptoms in patients with advanced squamous non-small cell lung cancer: results from the CheckMate 017 study. J Thorac Oncol. 2018 Feb;13(2):194–204.
   PubMed Web of Science ®Google Scholar
• Reck M, Brahmer J, Bennett B, et al. Evaluation of health-related quality of life and symptoms in patients with advanced non-squamous non-small cell lung cancer treated with nivolumab or docetaxel in CheckMate 057. Eur J Cancer. 2018 Oct;102:23–30.
   PubMed Web of Science ®Google Scholar
• Peters S, Felip E, Dafni U, et al. Safety evaluation of nivolumab added concurrently to radiotherapy in a standard first line chemo-radiotherapy regimen in stage III non-small cell lung cancer-the ETOP NICOLAS trial. Lung Cancer. 2019 Jul;133:83–87.
   PubMed Web of Science ®Google Scholar
• Peters S, Felip E, Dafni U, et al. Progression-free and overall survival for concurrent nivolumab with standard concurrent chemoradiotherapy in locally advanced stage IIIA-B NSCLC: results from the European thoracic oncology platform NICOLAS phase II trial (European thoracic oncology platform 6-14). J Thorac Oncol. 2021 Feb;16(2):278–288.
   PubMed Web of Science ®Google Scholar
• 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 Apr 30;387(10030):1837–1846.
   PubMed Web of Science ®Google Scholar
• Malhotra J, Jabbour SK, Aisner J. Current state of immunotherapy for non-small cell lung cancer. Transl Lung Cancer Res. 2017;6(2):196–211.
   PubMed Web of Science ®Google Scholar
• Kuon J, Hommertgen A, Krisam J, et al. Durvalumab in frail and elderly patients with stage four non-small cell lung cancer: study protocol of the randomized phase II DURATION trial. Trials. 2020 Apr 22;21(1):352.
   PubMedGoogle Scholar
• Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2017 Nov 16;377(20):1919–1929.
   PubMed Web of Science ®Google Scholar
• Antonia SJ, Villegas A, Daniel D, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018 Dec 13;379(24):2342–2350.
   PubMed Web of Science ®Google Scholar
• Spigel DR, Faivre-Finn C, Gray JE, et al. Five-year survival outcomes with durvalumab after chemoradiotherapy in unresectable stage III NSCLC: an update from the PACIFIC trial. J clin oncol. 2021. 2021 05 20;39(15_suppl):8511.
   Web of Science ®Google Scholar
• Administration FnD [webpage on the Internet]. FDA expands approval of imfinzi to reduce the risk of non-small cell lung cancer progressing. 2018 [ cited 2020 Dec 14]. Available from: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm597217.htm
   Google Scholar
• Planchard D, Yokoi T, McCleod MJ, et al. A phase III study of durvalumab (MEDI4736) with or without tremelimumab for previously treated patients with advanced NSCLC: rationale and protocol design of the arctic study. Clin Lung Cancer. 2016 May;17(3):232–236 e1.
   PubMed Web of Science ®Google Scholar
• Garassino MC, Cho BC, Kim JH, et al. Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study. Lancet Oncol. 2018 Apr;19(4):521–536.
   PubMed Web of Science ®Google Scholar
• Horn L, Mansfield AS, Szczesna A, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018 Dec 6;379(23):2220–2229.
   PubMed Web of Science ®Google Scholar
• Goldman JW, Dvorkin M, Chen Y, et al. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51–65.
   PubMed Web of Science ®Google Scholar
• Senan S, Okamoto I, Lee GW, et al. Design and rationale for a phase III, randomized, placebo-controlled trial of durvalumab with or without tremelimumab after concurrent chemoradiotherapy for patients with limited-stage small-cell lung cancer: the ADRIATIC study. Clin Lung Cancer. 2020 Mar;21(2):e84–e88.
   PubMed Web of Science ®Google Scholar
• Chung HC, Piha-Paul SA, Lopez-Martin J, et al. Pembrolizumab after two or more lines of previous therapy in patients with recurrent or metastatic SCLC: results from the KEYNOTE-028 and KEYNOTE-158 studies. J Thorac Oncol. 2020 Apr;15(4):618–627.
   PubMed Web of Science ®Google Scholar
• Antonia SJ, Lopez-Martin JA, Bendell J, et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016 Jul;17(7):883–895.
   PubMed Web of Science ®Google Scholar
• Yang S, Zhang Z, Wang Q. Emerging therapies for small cell lung cancer. J Hematol Oncol. 2019 May 2;12(1):47.
   PubMedGoogle Scholar
• Xia L, Liu Y, Wang Y. PD-1/PD-L1 blockade therapy in advanced non-small-cell lung cancer: current status and future directions. Oncologist. 2019 Feb;24(Suppl S1):S31–S41.
   PubMedGoogle Scholar
• Meyers DE, Bryan PM, Banerji S, et al. Targeting the PD-1/PD-L1 axis for the treatment of non-small-cell lung cancer. Curr Oncol. 2018 Aug;25(4):e324–e334.
   PubMed Web of Science ®Google Scholar
• Sanikini H, Yuan JM, Butler LM, et al. Body mass index and lung cancer risk: a pooled analysis based on nested case-control studies from four cohort studies. BMC Cancer. 2018 Feb 23;18(1):220.
   PubMedGoogle Scholar
• Yu D, Zheng W, Johansson M, et al. Overall and central obesity and risk of lung cancer: a pooled analysis. J Natl Cancer Inst. 2018 Aug 1;110(8):831–842.
   PubMedGoogle Scholar
• Yang H, Youm YH, Vandanmagsar B, et al. Obesity accelerates thymic aging. Blood. 2009 Oct 29;114(18):3803–3812.
   PubMed Web of Science ®Google Scholar
• Nieman DC, Henson DA, Nehlsen-Cannarella SL, et al. Influence of obesity on immune function. J Am Diet Assoc. 1999 Mar;99(3):294–299.
   PubMed Web of Science ®Google Scholar
• Wang Z, Aguilar EG, Luna JI, et al. Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade. Nat Med. 2019 Jan;25(1):141–151.
   PubMed Web of Science ®Google Scholar
• Ichihara E, Harada D, Inoue K, et al. The impact of body mass index on the efficacy of anti-PD-1/PD-L1 antibodies in patients with non-small cell lung cancer. Lung Cancer. 2020 Jan;139:140–145.
   PubMed Web of Science ®Google Scholar
• Kichenadasse G, Miners JO, and Mangoni AA, et al. Association between body mass index and overall survival with immune checkpoint inhibitor therapy for advanced non-small cell lung cancer. JAMA Oncol. 2019 ;6(4): 512–518 .
   Web of Science ®Google Scholar
• McQuade JL, Daniel CR, Hess KR, et al. Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: a retrospective, multicohort analysis. Lancet Oncol. 2018 Mar;19(3):310–322.
   PubMed Web of Science ®Google Scholar
• Lam VK, Bentzen SM, Mohindra P, et al. Obesity is associated with long-term improved survival in definitively treated locally advanced non-small cell lung cancer (NSCLC). Lung Cancer. 2017 Feb;104:52–57.
   PubMed Web of Science ®Google Scholar
• Sivan A, Corrales L, Hubert N, et al. Commensal bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015 Nov 27;350(6264):1084–1089.
   PubMed Web of Science ®Google Scholar
• Watanabe S, Kikuchi T. Does the gut microbiota play a key role in PD-1/PD-L1 blockade therapy? Transl Lung Cancer Res. 2020 Jun;9(3):438–440.
   PubMed Web of Science ®Google Scholar
• Gopalakrishnan V, Spencer CN, Nezi L, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018 Jan 5;359(6371):97–103.
   PubMed Web of Science ®Google Scholar
• Routy B, Le Chatelier E, Derosa L, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018 Jan 5;359(6371):91–97.
   PubMed Web of Science ®Google Scholar
• Suh KJ, Kim SH, Kim YJ, et al. Post-treatment neutrophil-to-lymphocyte ratio at week 6 is prognostic in patients with advanced non-small cell lung cancers treated with anti-PD-1 antibody. Cancer Immunol Immunother. 2018 Mar;67(3):459–470.
   PubMed Web of Science ®Google Scholar
• Xiong Q, Huang Z, and Xin L, et al. Post-treatment neutrophil-to-lymphocyte ratio (NLR) predicts response to anti-PD-1/PD-L1 antibody in SCLC patients at early phase. Cancer Immunol Immunother. 2020;70(3):713–720 .
   PubMed Web of Science ®Google Scholar
• Ethier JL, Desautels D, Templeton A, et al. Prognostic role of neutrophil-to-lymphocyte ratio in breast cancer: a systematic review and meta-analysis. Breast Cancer Res. 2017 Jan 5;19(1):2.
   PubMed Web of Science ®Google Scholar
• Chen N, Liu S, Huang L, et al. Prognostic significance of neutrophil-to-lymphocyte ratio in patients with malignant pleural mesothelioma: a meta-analysis. Oncotarget. 2017 Aug 22;8(34):57460–57469.
   PubMedGoogle Scholar
• Ferris RL, Blumenschein G Jr., Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016 Nov 10;375(19):1856–1867.
   PubMed Web of Science ®Google Scholar
• Segal NH, Ou SI, Balmanoukian A, et al. Safety and efficacy of durvalumab in patients with head and neck squamous cell carcinoma: results from a phase I/II expansion cohort. Eur J Cancer. 2019 Mar;109:154–161.
   PubMed Web of Science ®Google Scholar
• Aguiar PN Jr., De Mello RA, Hall P, et al. PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: updated survival data. Immunotherapy. 2017 May;9(6):499–506.
   PubMed Web of Science ®Google Scholar
• Buttner R, Gosney JR, Skov BG, et al. Programmed death-ligand 1 immunohistochemistry testing: a review of analytical assays and clinical implementation in non-small-cell lung cancer. J Clin Oncol. 2017 Dec 1;35(34):3867–3876.
   PubMed Web of Science ®Google Scholar
• Hirsch FR, McElhinny A, Stanforth D, 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 Feb;12(2):208–222.
   PubMed Web of Science ®Google Scholar
• Meng X, Gao Y, Yang L, et al. Immune microenvironment differences between squamous and non-squamous non–small-cell lung cancer and their influence on the prognosis. Clin Lung Cancer. 2019. 2019 01 01;20(1):48–58.
   PubMed Web of Science ®Google Scholar
• Zhou C, Tang J, and Sun H, et al. PD-L1 expression as poor prognostic factor in patients with non-squamous non-small cell lung cancer. Oncotarget. 2017;8(35):58457–58468.
   PubMedGoogle Scholar
• McLaughlin J, Han G, Schalper KA, et al. Quantitative assessment of the heterogeneity of PD-L1 expression in non–small-cell lung cancer. JAMA Oncol. 2016;2(1):46–54.
   PubMed Web of Science ®Google Scholar
• Fujimoto D, Uehara K, Sato Y, et al. Alteration of PD-L1 expression and its prognostic impact after concurrent chemoradiation therapy in non-small cell lung cancer patients. Sci Rep. 2017 Sep 12;7(1):11373.
   PubMedGoogle Scholar
• Ilie M, Long-Mira E, Bence C, et al. Comparative study of the PD-L1 status between surgically resected specimens and matched biopsies of NSCLC patients reveal major discordances: a potential issue for anti-PD-L1 therapeutic strategies. Ann Oncol. 2016 Jan;27(1):147–153.
   PubMed Web of Science ®Google Scholar
• Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015 Apr 3;348(6230):124–128.
   PubMed Web of Science ®Google Scholar
• Chalmers ZR, Connelly CF, Fabrizio D, et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 2017 Apr 19;9(1):34.
   PubMed Web of Science ®Google Scholar
• Hellmann MD, Callahan MK, Awad MM, et al. Tumor mutational burden and efficacy of Nivolumab monotherapy and in combination with ipilimumab in small-cell lung cancer. Cancer Cell. 2018 May 14;33(5):853–861 e4.
   PubMed Web of Science ®Google Scholar
• Hellmann MD, Nathanson T, Rizvi H, et al. Genomic features of response to combination immunotherapy in patients with advanced non-small-cell lung cancer. Cancer Cell. 2018 May 14;33(5):843–852 e4.
   PubMed Web of Science ®Google Scholar
• Marliot F, Lafontaine L, Galon J. Immunoscore assay for the immune classification of solid tumors: technical aspects, improvements and clinical perspectives. Methods Enzymol. 2020;636:109–128.
   PubMed Web of Science ®Google Scholar
• Pages F, Mlecnik B, Marliot F, et al. International validation of the consensus immunoscore for the classification of colon cancer: a prognostic and accuracy study. Lancet. 2018 May 26;391(10135):2128–2139.
   PubMed Web of Science ®Google Scholar
• Zhao Z, Zhao D, Xia J, et al. Immunoscore predicts survival in early-stage lung adenocarcinoma patients. Front Oncol. 2020;10:691.
   PubMed Web of Science ®Google Scholar
• Das S, Johnson DB. Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors. J Immunother Cancer. 2019 Nov 15;7(1):306.
   PubMed Web of Science ®Google Scholar
• Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015 Jun 25;372(26):2521–2532.
   PubMed Web of Science ®Google Scholar
• Kim KW, Ramaiya NH, Krajewski KM, et al. Ipilimumab associated hepatitis: imaging and clinicopathologic findings. Invest New Drugs. 2013 Aug;31(4):1071–1077.
   PubMed Web of Science ®Google Scholar
• Ryder M, Callahan M, Postow MA, et al. Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution. Endocr Relat Cancer. 2014 Apr;21(2):371–381.
   PubMed Web of Science ®Google Scholar
• Hamid O, Robert C, Daud A, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013 Jul 11;369(2):134–144.
   PubMed Web of Science ®Google Scholar
• Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010 Aug 19;363(8):711–723.
   PubMed Web of Science ®Google Scholar
• 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 Jun 28;366(26):2455–2465.
   PubMed Web of Science ®Google Scholar
• 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. 2014 Jun;15(7):700–712.
   PubMed Web of Science ®Google Scholar
• 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. 2015 Jun 20;33(18):2004–2012.
   PubMed Web of Science ®Google Scholar
• Herbst RS, Soria JC, Kowanetz M, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014 Nov 27;515(7528):563–567.
   PubMed Web of Science ®Google Scholar
• Wang PF, Chen Y, Song SY, et al. Immune-related adverse events associated with anti-PD-1/PD-L1 treatment for malignancies: a meta-analysis. Front Pharmacol. 2017;8:730.
   PubMed Web of Science ®Google Scholar
• Coleman E, Ko C, Dai F, et al. Inflammatory eruptions associated with immune checkpoint inhibitor therapy: a single-institution retrospective analysis with stratification of reactions by toxicity and implications for management. J Am Acad Dermatol. 2019 Apr;80(4):990–997.
   PubMed Web of Science ®Google Scholar
• Raschi E, Mazzarella A, Antonazzo IC, et al. Toxicities with immune checkpoint inhibitors: emerging priorities from disproportionality analysis of the FDA adverse event reporting system. Target Oncol. 2019 Apr;14(2):205–221.
   PubMed Web of Science ®Google Scholar
• Weber JS, Dummer R, de Pril V, et al. Patterns of onset and resolution of immune-related adverse events of special interest with ipilimumab: detailed safety analysis from a phase 3 trial in patients with advanced melanoma. Cancer. 2013 May 1;119(9):1675–1682.
   PubMed Web of Science ®Google Scholar
• Beck KE, Blansfield JA, Tran KQ, et al. Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4. J Clin Oncol. 2006 May 20;24(15):2283–2289.
   PubMed Web of Science ®Google Scholar
• Iwamoto K, Ishitsuka Y, Tanaka R, et al. Azathioprine combination therapy for steroid-refractory hepatic immune system-related adverse events. Eur J Dermatol. 2017 Jun 1;27(3):301–303.
   PubMed Web of Science ®Google Scholar
• Gubin MM, Zhang X, Schuster H, et al. Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature. 2014 Nov 27;515(7528):577–581.
   PubMed Web of Science ®Google Scholar
• Chodon T, Comin-Anduix B, Chmielowski B, et al. Adoptive transfer of MART-1 T-cell receptor transgenic lymphocytes and dendritic cell vaccination in patients with metastatic melanoma. Clin Cancer Res. 2014 May 1;20(9):2457–2465.
   PubMed Web of Science ®Google Scholar
• Liu C, Peng W, Xu C, et al. BRAF inhibition increases tumor infiltration by T cells and enhances the antitumor activity of adoptive immunotherapy in mice. Clin Cancer Res. 2013 Jan 15;19(2):393–403.
   PubMed Web of Science ®Google Scholar
• Peng W, Chen JQ, Liu C, et al. Loss of PTEN promotes resistance to T cell-mediated immunotherapy. Cancer Discov. 2016 Feb;6(2):202–216.
   PubMed Web of Science ®Google Scholar
• Spranger S, Bao R, Gajewski TF. Melanoma-intrinsic beta-catenin signalling prevents anti-tumour immunity. Nature. 2015 Jul 9;523(7559):231–235.
   PubMed Web of Science ®Google Scholar
• Wen L, Lu H, Li Q, et al. Contributions of T cell dysfunction to the resistance against anti-PD-1 therapy in oral carcinogenesis. J Exp Clin Cancer Res. 2019 Jul 10;38(1):299.
   PubMedGoogle Scholar
• Sade-Feldman M, Jiao YJ, Chen JH, et al. Resistance to checkpoint blockade therapy through inactivation of antigen presentation. Nat Commun. 2017 Oct 26;8(1):1136.
   PubMed Web of Science ®Google Scholar
• Shin DS, Zaretsky JM, Escuin-Ordinas H, et al. Primary resistance to PD-1 blockade mediated by JAK1/2 mutations. Cancer Discov. 2017 Feb;7(2):188–201.
   PubMed Web of Science ®Google Scholar
• Benci JL, Xu B, Qiu Y, et al. Tumor interferon signaling regulates a multigenic resistance program to immune checkpoint blockade. Cell. 2016 Dec 1;167(6):1540–1554 e12.
   PubMed Web of Science ®Google Scholar
• Zaretsky JM, Garcia-Diaz A, Shin DS, et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med. 2016 Sep 1;375(9):819–829.
   PubMed Web of Science ®Google Scholar
• Zemek RM, De Jong E, Chin WL, et al. Sensitization to immune checkpoint blockade through activation of a STAT1/NK axis in the tumor microenvironment. Sci Transl Med. 2019 Jul 17;11(501). DOI:https://doi.org/10.1126/scitranslmed.aav7816.
   Google Scholar
• Koyama S, Akbay EA, Li YY, et al. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun. 2016 Feb 17;7(1):10501.
   PubMed Web of Science ®Google Scholar
• Corrales L, Glickman LH, McWhirter SM, et al. Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity. Cell Rep. 2015 May 19;11(7):1018–1030.
   PubMed Web of Science ®Google Scholar
• Holmgaard RB, Zamarin D, Munn DH, et al. Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4. J Exp Med. 2013 Jul 1;210(7):1389–1402.
   PubMed Web of Science ®Google Scholar
• Beatty GL, Haas AR, Maus MV, et al. Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer Immunol Res. 2014 Feb;2(2):112–120.
   PubMed Web of Science ®Google Scholar
• Homet Moreno B, Mok S, Comin-Anduix B, et al. Combined treatment with dabrafenib and trametinib with immune-stimulating antibodies for BRAF mutant melanoma. Oncoimmunology. 2016 Jul;5(7):e1052212.
   PubMed Web of Science ®Google Scholar
• Sakuishi K, Apetoh L, Sullivan JM, et al. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med. 2010 Sep 27;207(10):2187–2194.
   PubMed Web of Science ®Google Scholar
• Champiat S, Dercle L, Ammari 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 Apr 15;23(8):1920–1928.
   PubMed Web of Science ®Google Scholar
• Ferrara R, Mezquita L, Texier M, et al. Hyperprogressive disease in patients with advanced non-small cell lung cancer treated with PD-1/PD-L1 inhibitors or with single-agent chemotherapy. JAMA Oncol. 2018 Nov 1;4(11):1543–1552.
   PubMed Web of Science ®Google Scholar
• Kim CG, Kim KH, Pyo KH, et al. Hyperprogressive disease during PD-1/PD-L1 blockade in patients with non-small-cell lung cancer. Ann Oncol. 2019 Jul 1;30(7):1104–1113.
   PubMed Web of Science ®Google Scholar
• Lo Russo G, Moro M, Sommariva M, et al. Antibody-Fc/FcR interaction on macrophages as a mechanism for hyperprogressive disease in non-small cell lung cancer subsequent to PD-1/PD-L1 blockade. Clin Cancer Res. 2019 Feb 1;25(3):989–999.
   PubMed Web of Science ®Google Scholar
• Grecea M, Marabelle A, Ammari S, et al. Managing hyperprogressive disease in the era of programmed cell death Protein 1/programmed death-ligand 1 blockade: a case discussion and review of the literature. Oncologist. 2020 May;25(5):369–374.
   PubMed Web of Science ®Google Scholar
• Weiss GJ, Beck J, Braun DP, et al. Tumor cell-free DNA copy number instability predicts therapeutic response to immunotherapy. Clin Cancer Res. 2017 Sep 1;23(17):5074–5081.
   PubMed Web of Science ®Google Scholar
• Zuazo-Ibarra M, Arasanz H, and Fernández-Hinojal G, et al. Highly differentiated CD4 T cells Unequivocally Identify Primary Resistance and Risk of Hyperprogression to PDL1/PD-1 Immune Checkpoint Blockade in Lung Cancer (New York, United States: Cold Spring Harbor Laboratory). 2018.
   Google Scholar
• Kato S, Goodman A, Walavalkar V, et al. Hyperprogressors after immunotherapy: analysis of genomic alterations associated with accelerated growth rate. Clin Cancer Res. 2017 Aug 1;23(15):4242–4250.
   PubMed Web of Science ®Google Scholar
• Saada-Bouzid E, Defaucheux C, Karabajakian A, et al. Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Ann Oncol. 2017 Jul 1;28(7):1605–1611.
   PubMed Web of Science ®Google Scholar
• PD-L1 IHC 28–8 pharmDx - P150025/S013 FDA approval. [ cited 2020 Dec 15]. Available from: https://www.fda.gov/medical-devices/recently-approved-devices/pd-l1-ihc-28-8-pharmdx-p150025s013
   Google Scholar
• PD-L1 IHC 22C3 pharmDx - P150013/S011 FDA approval. [ cited 2020 Dec 15]. Available from: https://www.fda.gov/medical-devices/recently-approved-devices/pd-l1-ihc-22c3-pharmdx-p150013s011
   Google Scholar
• VENTANA PD-L1 (SP142) assay - P160002/S009 FDA approval. [ cited 2020 Dec 15]. Available from: https://www.fda.gov/medical-devices/recently-approved-devices/ventana-pd-l1-sp142-assay-p160002s009
   Google Scholar
• VENTANA PD-L1 (SP263) ASSAY FDA approval. [ cited 2020 Dec 15]. Available from: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?ID=394004
   Google Scholar