PD-L1 expression in advanced NSCLC: Insights into risk stratification and treatment selection from a systematic literature review

Lung Cancer

Volumn 112, Issue , 2017, Pages 200-215

  Brody, Robert ^a   Zhang, Yiduo ^a   Ballas, Marc ^a   Siddiqui, Mohd Kashif ^b   Gupta, Palvi ^b   Barker, Craig ^a   Midha, Anita ^a   Walker, Jill ^a  

^a ASTRAZENECA   (United Kingdom)

^b PAREXEL INTERNATIONAL   (United States)

Author keywords

Advanced NSCLC; Assay; Checkpoint inhibitors; Immunohistochemistry; PD L1; Prognosis

Indexed keywords

ANAPLASTIC LYMPHOMA KINASE; ATEZOLIZUMAB; AVELUMAB; DURVALUMAB; EPIDERMAL GROWTH FACTOR RECEPTOR; IPILIMUMAB; K RAS PROTEIN; NIVOLUMAB; PEMBROLIZUMAB; PROGRAMMED DEATH 1 LIGAND 1; TICILIMUMAB; TUMOR MARKER;

ADVANCED CANCER; AGE; ANTIBODY DETECTION; CANCER GRADING; CANCER PATIENT; CANCER PROGNOSIS; CANCER RADIOTHERAPY; CANCER STAGING; CANCER SURVIVAL; CANCER TISSUE; CLINICAL FEATURE; GENDER; GENE MUTATION; HUMAN; IMMUNOHISTOCHEMISTRY; LUNG ADENOCARCINOMA; METASTASIS; NON SMALL CELL LUNG CANCER; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SMOKING; SQUAMOUS CELL LUNG CARCINOMA; SYSTEMATIC REVIEW; TREATMENT OUTCOME; ANTAGONISTS AND INHIBITORS; FEMALE; GENE EXPRESSION; GENETICS; LUNG TUMOR; MALE; META ANALYSIS; METABOLISM; MOLECULARLY TARGETED THERAPY; MORTALITY; PATHOLOGY; PROGNOSIS; SURVIVAL ANALYSIS;

B7-H1 ANTIGEN; BIOMARKERS, TUMOR; CARCINOMA, NON-SMALL-CELL LUNG; FEMALE; GENE EXPRESSION; HUMANS; LUNG NEOPLASMS; MALE; MOLECULAR TARGETED THERAPY; NEOPLASM METASTASIS; NEOPLASM STAGING; PROGNOSIS; SURVIVAL ANALYSIS; TREATMENT OUTCOME;

EID: 85029163151     PISSN: 01695002     EISSN: 18728332     Source Type: Journal    
DOI: 10.1016/j.lungcan.2017.08.005     Document Type: Review

References (123)

1. Syrigos, K.N., Saif, M.W., Karapanagiotou, E.M., Oikonomopoulos, G., De Marinis, F., The need for third-line treatment in non-small cell lung cancer: an overview of new options. Anticancer Res. 31:2 (2011), 649–659.
2. Pardoll, D.M., The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 12:4 (2012), 252–264.
3. Postow, M.A., Callahan, M.K., Wolchok, J.D., Immune checkpoint blockade in cancer therapy. J. Clin. Oncol. 33:17 (2015), 1974–1982.
4. Borghaei, H., Paz-Ares, L., Horn, L., Spigel, D.R., Steins, M., Ready, N.E., et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N. Engl. J. Med. 373:17 (2015), 1627–1639.
5. Garon, E.B., Rizvi, N.A., Hui, R., Leighl, N., Balmanoukian, A.S., Eder, J.P., et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N. Engl. J. Med. 372:21 (2015), 2018–2028.
6. Gulley, J.L., Spigel, D., Kelly, K.C., CJ, Rajan, A., Hassan, R., 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. J. Clin. Oncol., 33(Suppl. 15), 2015, 8034 (abstr).
7. Rizvi, N.A., Brahmer, J.R., Ou, S.-H.I., Segal, N.H., Khleif, S., Hwu, W.-J., et al. Safety and clinical activity of MEDI4736, an anti-programmed cell death-ligand 1 (PD-L1) antibody, in patients with non-small cell lung cancer (NSCLC). J. Clin. Oncol., 33(Suppl. 15), 2015, 8032 (abstr).
8. Spigel, D.R., Chaft, J.E., Gettinger, S.N., Chao, B.H., Dirix, L.Y., Schmid, P., et al. Clinical activity and safety from a phase II study (FIR) of atezolizumab (anti-PDL1) in PD-L1–selected patients with non-small cell lung cancer (NSCLC). J. Clin. Oncol., 33(Suppl. 15), 2015, 8028 (abstr).
9. Boyd, Z.S., Smith, D.C., Baker, B., Vennapusa, B., Koeppen, H., Kowanetz, M., et al. Development of a PD-L1 companion diagnostic IHC assay (SP142) for atezolizumab. Cancer Immunol. Res., 4(Suppl. 1), 2016, B001 (abstr).
10. Dolled-Filhart, M., Roach, C.M., Toland, G., Musser, J., Lubiniecki, G.M., Ponto, G., et al. Development of a PD-L1 immunohistochemistry (IHC) assay for use as a companion diagnostic for pembrolizumab (MK-3475) in non-small cell lung cancer (NSCLC). J. Clin. Oncol., 33(Suppl. 15), 2015, 11065 (abstr).
11. Food and Drug Administration (FDA). Dako PD-L1 IHC 28-8 pharmDx. October 2015. Last accessed 10 August 20162015. Available from: http://www.accessdata.fda.gov/cdrh_docs/pdf15/P150025c.pdf.
12. Food and Drug Administration (FDA). Dako PD-L1 IHC 22C3 pharmDx. September 2015. Last accessed 10 August 20162015. Available from: http://www.accessdata.fda.gov/cdrh_docs/pdf15/P150013c.pdf.
13. Phillips, T., Simmons, P., Inzunza, H.D., Cogswell, J., Novotny, J. Jr., Taylor, C., et al. Development of an automated PD-L1 immunohistochemistry (IHC) assay for non-small cell lung cancer. Appl. Immunohistochem. Mol. Morphol. 23:8 (2015), 541–549.
14. Rebelatto, M., Mistry, A., Sabalos, C., Walker, J., Midha, A., Steele, K., et al. Development of a PD-L1 companion diagnostic assay for treatment with MEDI4736 in NSCLC and SCCHN patients. J. Clin. Oncol., 33(Suppl. 15), 2015, 8033 (abstr).
15. Kerr, K.M., Hirsch, F.R., Programmed death ligand 1 immunohistochemistry: friend or foe?. Arch. Pathol. Lab. Med. 140:4 (2016), 326–331.
16. Mahoney, K.M., Sun, H., Liao, X., Hua, P., Callea, M., Greenfield, E.A., et al. PD-L1 antibodies to its cytoplasmic domain most clearly delineate cell membranes in immunohistochemical staining of tumor cells. Cancer Immunol. Res. 3:12 (2015), 1308–1315.
17. McLaughlin, J., Han, G., Schalper, K.A., Carvajal-Hausdorf, D., Pelakanou, V., Rehman, J., et al. Quantitative assessment of the heterogeneity of PD-L1 expression in non–small-cell lung cancer. JAMA Oncol. 2:1 (2016), 46–54.
18. Sholl, L.M., Aisner, D.L., Allen, T.C., Beasley, M.B., Borczuk, A.C., Cagle, P.T., et al. Programmed death ligand 1 immunohistochemistry - a new challenge for pathologists: a perspective from members of the pulmonary pathology society. Arch. Pathol. Lab. Med. 140:4 (2016), 341–344.
19. Cooper, W.A., Tran, T., Vilain, R.E., Madore, J., Selinger, C.I., Kohonen-Corish, M., et al. PD-L1 expression is a favorable prognostic factor in early stage non-small cell carcinoma. Lung Cancer (Amsterdam, Netherlands) 89:2 (2015), 181–188.
20. Mu, C.Y., Huang, J.A., Chen, Y., Chen, C., Zhang, X.G., 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. (Northwood, Lond., Engl.) 28:3 (2011), 682–688.
21. Schmidt, L.H., Kummel, A., Gorlich, D., Mohr, M., Bröckling, S., Mikesch, J.H., et al. PD-1 and PD-L1 expression in NSCLC indicate a favorable prognosis in defined subgroups. PLoS One, 10(8), 2015, e0136023.
22. Ilie, M., Hofman, V., Dietel, M., Soria, J.C., Hofman, P., Assessment of the PD-L1 status by immunohistochemistry: challenges and perspectives for therapeutic strategies in lung cancer patients. Virchows Arch. 468:5 (2016), 511–525.
23. Food and Drug Administration (FDA). VENTANA PD-L1 (SP142) Assay. Last accessed 10 January 20162016. Available from: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma_template.cfm?id=p160006.
24. Ventana Medical Systems. Ventana PD-L1 (SP263) assay is a qualitative IHC assay using rabbit monoclonal anti-PD-L1 clone SP263 intended for use in the assessment of the PD-L1 protein in formalin-fixed, paraffin-embedded (FFPE) urothelial carcinoma tissue. Last accessed 19 May 2017. Available from: http://productlibrary.ventana.com/ventana_portal/OpenOverlayServlet?launchIndex=1&objectId=740-49071014737US.
25. Ventana Medical Systems. VENTANA PD-L1 (SP263) Rabbit Monoclonal Primary Antibody is intended for laboratory use in the detection of the PD-L1 protein in formalin-fixed, paraffin-embedded tissue. It is indicated as an aid in the assessment of PD-L1 expression in non-small cell lung cancer (NSCLC) and other tumor types. Last accessed 19 May 2017. Available from: http://productlibrary.ventana.com/ventana_portal/OpenOverlayServlet?launchIndex=2&objectId=790-49051014247US.
26. Hirsch, F.R., 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. 12:2 (2017), 208–222.
27. Ratcliffe, M.J., Sharpe, A., Midha, A., Barker, C., Scott, M., Scorer, P., et al. Agreement between programmed cell death ligand-1 diagnostic assays across multiple protein expression cut-offs in non-small cell lung cancer. Clin. Cancer Res. 23:14 (2017), 3585–3591.
28. Velcheti, V., Schalper, K.A., Carvajal, D.E., Anagnostou, V.K., Syrigos, K.N., Sznol, M., et al. Programmed death ligand-1 expression in non-small cell lung cancer. Lab. Invest. 94:1 (2014), 107–116.
29. Mao, Y., Li, W., Chen, K., Xie, Y., Liu, Q., Yao, M., et al. B7-H1 and B7-H3 are independent predictors of poor prognosis in patients with non-small cell lung cancer. Oncotarget 6:5 (2015), 3452–3461.
30. Zhang, J., Gao, J., Li, Y., Nie, J., Dai, L., Hu, W., et al. Circulating PD-L1 in NSCLC patients and the correlation between the level of PD-L1 expression and the clinical characteristics. Thorac. Cancer 6:4 (2015), 534–538.
31. Sasaki, H., Suzuki, A., Shitara, M., Hikosaka, Y., Okuda, K., Moriyama, S., et al. PD-L1 gene expression in Japanese lung cancer patients. Biomed. Rep. 1:1 (2013), 93–96.
32. Spira, A.I., Park, K., Mazières, J., Vansteenkiste, J.F., Rittmeyer, A., Ballinger, M., et al. Efficacy, safety and predictive biomarker results from a randomized phase II study comparing MPDL3280A vs docetaxel in 2L/3L NSCLC (POPLAR). J. Clin. Oncol., 33(Suppl. 15), 2015, 8010 (abstr).
33. Besse, B., Johnson, M., Jänne, P.A., Garassino, M., Eberhardt, W.E., Peters, S., et al. Phase II, single-arm trial (BIRCH) of atezolizumab as first-line or subsequent therapy for locally advanced or metastatic PD-L1-selected non-small cell lung cancer (NSCLC). Eur. J. Cancer, 51(Suppl. 3), 2015.
34. Liu, S.V., Powderly, J.D., Camidge, D.R., Ready, N., Heist, R.S., Hodi, F.S., et al. Safety and efficacy of MPDL3280A (anti-PDL1) in combination with platinum based doublet chemotherapy in patients with advanced nonsmall cell lung cancer (NSCLC). J. Clin. Oncol., 15(Suppl. 15), 2015, 8030 (abstr.).
35. Herbst, R.S., Soria, J.C., Kowanetz, M., Fine, G.D., Hamid, O., Gordon, M.S., et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 515:7528 (2014), 563–567.
36. Antonia, S.J., Goldberg, S.B., Balmanoukian, A.S., Sanborn, R.E., Steele, K., Narwal, R., 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. J. Clin. Oncol., 33(Suppl. 15), 2015, 3014 (abstr).
37. Rebelatto, M.C., Mistry, A., Sabalos, C., Schechter, N., Walker, J., Midha, A., et al. An immunohistochemical PD-L1 companion diagnostic assay for treatment with durvalumab (MEDI4736) in NSCLC patients. Cancer Immunol. Res., 4(Suppl. 1), 2016, B005 (abstr).
38. Ventana Medical Systems. Ventana PD-L1 (SP263) Assay. Last accessed 10 August 20162015. Available from: http://www.ventana.com/product/1815?type=2324.
39. Adam, J., Boros, A., Lacas, B., Lacroix, L., Pignon, J.P., Carmella, C., et al. Prognostic value of PDL1 expression in stage III non-small cell lung cancer (NSCLC) treated by chemo-radiotherapy (CRT). Eur. J. Cancer, 51(Suppl. 3), 2015, S604.
40. Gainor, J.F., Sequist, L.V., Shaw, A.T., Azzoli, C.G., Piotrowska, Z., Huynh, T., et al. Clinical correlation and frequency of programmed death ligand-1 (PD-L1) expression in EGFR-mutant and ALK-rearranged non-small cell lung cancer (NSCLC). J. Clin. Oncol., 33(Suppl. 5), 2015, 8012 (abstr).
41. Tang, Y., Fang, W., Zhang, Y., Hong, S., Kang, S., Yan, Y., et al. The association between PD-L1 and EGFR status and the prognostic value of PD-L1 in advanced non-small cell lung cancer patients treated with EGFR-TKIs. Oncotarget 6:16 (2015), 14209–14219.
42. Paz-Ares, L., Horn, L., Borghaei, H., Spigel, D.R., Steins, M., Ready, N., et al. Phase III, randomized trial (CheckMate 057) of nivolumab (NIVO) versus docetaxel (DOC) in advanced nonsquamous cell (non-SQ) non-small cell lung cancer (NSCLC). J. Clin. Oncol., 33(Suppl. 15), 2015, LBA109 (abstr).
43. Brahmer, J., Reckamp, K.L., Baas, P., Crinò, L., Eberhardt, W.E., Poddubskaya, E., et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N. Engl. J. Med. 373:2 (2015), 123–135.
44. Spigel, D.R., Reckamp, K.L., Rizvi, N.A., Poddubskaya, E., West, H.J., Eberhardt, W.E., et al. A phase III study (CheckMate 017) of nivolumab (NIVO; antiprogrammed death-1 [PD-1]) vs docetaxel (DOC) in previously treated advanced or metastatic squamous (SQ) cell non-small cell lung cancer (NSCLC). J. Clin. Oncol., 33(Suppl. 15), 2015, 8009 (abstr).
45. Rizvi, N.A., Shepherd, F.A., Antonia, S.J., Brahmer, J.R., Chow, L.Q., Goldman, J., et al. First-line monotherapy with nivolumab (Anti-PD-1; BMS-936558, ONO-4538) in advanced non-small cell lung cancer (NSCLC): safety, efficacy, and correlation of outcomes with PD-L1 status. Int. J. Rad. Oncol., 90(Suppl. 5), 2014.
46. Gettinger, S.N., Hellmann, M.D., Shepherd, F.A., Antonia, S.J., Brahmer, J., Chow, L.Q., et al. First-line nivolumab monotherapy with nivolumab (NIVO) in advanced non-small cell lung cancer (NSCLC): safety, efficacy, and biomarker analyses. Eur. J. Cancer, 51(Suppl. 3), 2015, S632.
47. Gettinger, S.N., Hellmann, M.D., Shepherd, F.A., Antonia, S.J., Brahmer, J.R., Chow, L.Q., 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. J. Clin. Oncol., 33(Suppl. 15), 2015, 8025 (abstr).
48. Gettinger, S.N., Shepherd, F.A., Antonia, S.J., Brahmer, J.R., Chow, L.Q., Juergens, R.A., et al. First-line nivolumab (anti-PD-1; BMS-936558, ONO-4538) monotherapy in advanced NSCLC: safety, efficacy, and correlation of outcomes with PD-L1 status. J. Clin. Oncol., 32(Suppl. 15), 2014, 8024 (abstr).
49. Rizvi, N.A., Mazières, J., Planchard, D., Stinchcombe, T.E., Dy, G.K., Antonia, S.J., et al. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 16:3 (2015), 257–265.
50. Feng, Y., Wang, X., Agrawal, S., Lestini, B., Park, J., Roy, A., Nivolumab exposure-response (E-R) analysis for clinical development of nivolumab in advanced refractory squamous non-small cell lung cancer. Clin. Pharmacol. Ther. 97:Suppl. 1 (2015), S57–S58.
51. Zalcman, G., Rizvi, N.A., Lena, H., Wolf, J., Mazieres, J., Antonia, S.J., et al. Phase 2 study of nivolumab (anti-programmed death-1 [PD-1]) in patients (pts) with advanced, refractory squamous (SQ) non-small cell lung cancer (NSCLC). Ann. Oncol., 26(Suppl. 1), 2015.
52. Gettinger, S.N., Horn, L., Gandhi, L., Spigel, D.R., Antonia, S.J., Rizvi, N.A., 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 (2015), 2004–2012.
53. Antonia, S.J., Grosso, J.F., Horak, C.E., Harbison, C., Kurland, J.F., Inzunza, H.D., et al. Association of tumor PD-L1 expression and immune biomarkers with clinical activity in patients with non-small cell lung cancer (NSCLC) treated with nivolumab (anti-PD-1; BMS- 936558; ONO-4538). J. Thorac. Oncol., 8(Suppl. 2), 2013.
54. Brahmer, J.R., Horn, L., Antonia, S.J., Spigel, D., Gandhi, L., Sequist, L.V., et al. Nivolumab (anti-PD-1; BMS-936558; ONO- 4538) in patients with non-small cell lung cancer (NSCLC): overall survival and long-term safety in a phase 1 trial. J. Thorac. Oncol., 8(Suppl.2), 2013.
55. Brahmer, J.R., Horn, L., Gandhi, L., Spigel, D.R., Antonia, S.J., Rizvi, N.A., et al. Nivolumab (anti-PD-1, BMS-936558, ONO-4538) in patients (pts) with advanced non-small-cell lung cancer (NSCLC): survival and clinical activity by subgroup analysis. J. Clin. Oncol., 32(Suppl. 15), 2014, 8112 (abstr).
56. Brahmer, J.R., Horn, L., Antonia, S.J., Spigel, D.R., Sequist, L.V., Ahlers, C.M., et al. Clinical activity, safety and subpopulation response analysis of nivolumab (anti-PD-1; BMS-936558; ONO-4538) in patients (PT) with non-small cell lung cancer (NSCLC). J. Thorac. Oncol., 9(Suppl. 1 (4)), 2014.
57. Gettinger, S., Horn, L., Antonia, S.J., Spigel, D.R., Gandhi, L., Sequist, L.V., et al. Efficacy of nivolumab (anti-PD-1; BMS- 936558; ONO-4538) in patients with previously treated advanced non-small cell lung cancer (NSCLC): subpopulation response analysis in a phase 1 trial. J. Thorac. Oncol., 8(Suppl. 2), 2013, S909.
58. Gettinger, S.N., Horn, L., Gandhi, L., Spigel, D.R., Antonia, S.J., Rizvi, N.A., et al. Long-term survival, clinical activity, and safety of nivolumab (anti-PD-1; BMS-936558, ONO-4538) in patients (PTS) with advanced non-small cell lung cancer (NSCLC). Int. J. Rad. Oncol. Biol. Phys., 90(Suppl. 5), 2014.
59. Hodi, F.S., Topalian, S.L., Brahmer, J.R., McDermott, D.F., Smith, D.C., Gettinger, S., et al. Survival and long-term safety in patients (pts) with advanced solid tumors receiving nivolumab (anti-PD-1; BMS-936558; ONO-4538). Eur. J. Cancer, 49(Suppl. 2), 2013, S185.
60. Rizvi, N.A., Gettinger, S.N., Horn, L., Gandhi, L., Spigel, D.R., Powderly, J.D., et al. Nivolumab (anti-PD-1; BMS-936558, ONO-4538) in patients with advanced non-small cell lung cancer (NSCLC): survival and clinical activity by subgroup analysis. J. Thorac. Oncol., 9(Suppl. 3), 2014, S152.
61. Topalian, S.L., Hodi, F.S., Brahmer, J.R., Gettinger, S.N., Smith, D.C., McDermott, D.F., et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366:26 (2012), 2443–2454.
62. Hellmann, M.D., Rizvi, N., Gettinger, S.N., Goldman, J., Chow, L.Q., Juergens, R., et al. Safety and efficacy of first-line nivolumab (NIVO) and ipilimumab (IPI) in non-small cell lung cancer (NSCLC). Eur. J. Cancer, 51(Suppl. 3), 2015.
63. Antonia, S.J., Gettinger, S., Chow, L.Q., Juergens, R., Borghaei, H., Shen, Y., et al. Nivolumab and ipilimumab in first-line non-small-cell lung carcinoma (NSCLC): interim phase I results. Asia-Pac. J. Clin. Oncol., 10(Suppl. 8), 2014, 155.
64. Antonia, S.J., Gettinger, S., Goldman, L.Q., Chow, R., Juergens, H., Borghaei, H., 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): metastatic non-small cell lung cancer. Int. J. Rad. Oncol., 90(Suppl. 5), 2014.
65. Antonia, S.J., Gettinger, S.N., Chow, L.Q., Juergens, R.A., Borghaei, H., Shen, Y., et al. Nivolumab (anti-PD-1; BMS-936558, ONO-4538) and ipilimumab in first-line NSCLC: interim phase I results. J. Clin. Oncol., 32(Suppl. 15), 2014, 8023 (abstr).
66. Garon, E.B., Leighl, N.B., Rizvi, N.A., Blumenschein, G.R., Balmanoukian, A.S., Eder, J.P., et al. Safety and clinical activity of MK-3475 in previously treated patients (pts) with non-small cell lung cancer (NSCLC). J. Clin. Oncol., 32(Suppl. 15), 2014, 8020 (abstr).
67. Garon, E.B., Rizvi, N., Hui, R., Leighl, N.B., Balmanoukian, A.S., Eder, J.P., et al. Efficacy of pembrolizumab (MK-3475) and relationship with PD-L1 expression in patients with non-small cell lung cancer: findings from KEYNOTE-001. Cancer Res., 75(Suppl. 15), 2015, CT104 (abstr).
68. Soria, J.C., Flatten, O., Horn, L., Felip, E., Gandhi, L., Hui, R., et al. Efficacy and safety of pembrolizumab (pembro; MK-3475) for patients (pts) with previously treated advanced non-small cell lung cancer (NSCLC) enrolled in Keynote-001. Eur. J. Cancer, 51(Suppl. 3), 2015.
69. Rizvi, N.A., Hellmann, M.D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J.J., et al. Cancer immunology: mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348:6230 (2015), 124–128.
70. Balmanoukian, A.S., Rizvi, N.A., Garon, E.B., Patnaik, A., Gandhi, L., Leighl, N.B., et al. Safety and clinical activity of MK-3475 as initial therapy in patients with advanced non-small cell lung cancer (NSCLC). Int. J. Rad. Oncol. Biol. Phys., 90(5 Suppl), 2014.
71. Rizvi, N.A., Garon, E.B., Patnaik, A., Gandhi, L., Leighl, N.B., Balmanoukian, A.S., et al. Safety and clinical activity of MK-3475 as initial therapy in patients with advanced non-small cell lung cancer (NSCLC). J. Clin. Oncol., 32(Suppl. 15), 2014, 8007 (abstr).
72. Goldberg, S.B., Gettinger, S.N., Mahajan, A., Herbst, R.S., Chiang, A.C., Tsiouris, J., et al. Activity and safety of pembrolizumab in patients with metastatic non-small cell lung cancer with untreated brain metastases. J. Clin. Oncol., 33(Suppl. 15), 2015, 8035 (abstr).
73. Sorensen, S.F., Zhou, W., Dolled-Filhart, M., Georgsen, J.B., Wang, Z., Emancipator, K., et al. PD-L1 expression and survival among advanced non-small cell lung cancer (NSCLC) patients treated with chemotherapy. Ann. Oncol., 25(Suppl. 4), 2014, iv 457.
74. Gettinger, S.N., Kowanetz, M., Soria, J.-C., Gandhi, L., Horn, L., Gordon, M.S., et al. Molecular correlates of PD- status and predictive biomarkers in patients with non-small cell lung cancer (NSCLC) treated with the anti-PDL1 antibody MPDL3280A. J. Thorac. Oncol., 8(Suppl. 2), 2013.
75. Horn, L., Herbst, R.S., Spigel, D., Gettinger, S.N., Gordan, M.S., Hollebecque, A., et al. An analysis of the relationship of clinical activity to baseline EGFR status, PD-L1 expression and prior treatment history in patients with non-small cell lung cancer (NSCLC) following PD-L1 blockade with MPDL3280A (anti-PD-L1). J. Thorac. Oncol., 8(Suppl. 2), 2013, S364.
76. Horn, L., Spigel, D.R., Gettinger, S.N., Antonia, S.J., Gordon, M.S., Herbst, R.S., et al. Clinical activity, safety and predictive biomarkers of the engineered antibody atezolizumab (MPDL3280A, anti-PD-L1) in non-small cell lung cancer (NSCLC): update from a phase Ia study. J. Clin. Oncol., 33(Suppl. 15), 2015, 8029 (abstr).
77. Soria, J.C., Cruz, C., Bahleda, R., Delord, J.P., Horn, L., Herbst, R.S., et al. Clinical activity, safety and biomarkers of PD-L1 blockade in non-small cell lung cancer (NSCLC): additional analyses from a clinical study of the engineered antibody MPDL3280A (anti-PD-L1). Eur. J. Cancer, 49(Suppl. 2), 2013, S798.
78. Spigel, D.R., Gettinger, S.N., Horn, L., Herbst, R.S., Gandhi, L., Gordon, M.S., et al. Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). J. Clin. Oncol., 31(Suppl. 15), 2013, 8008 (abstr).
79. Schmid, P., Kowanetz, M., Koeppen, H., Zou, W., Wistuba, I., Kockx, M., et al. NSCLC with high PD-L1 expression on tumor cells or tumor-infiltrating immune cells represents distinct cancer subtypes. Eur. J. Cancer, 51(Suppl. 3), 2015, S602.
80. Vansteenkiste, J., Vansteenkiste, J., Fehrenbacher, L., Spira, A.I., Mazieres, J., Park, K., et al. Atezolizumab monotherapy vs docetaxel in 2L/3L non-small cell lung cancer: primary analyses for efficacy, safety and predictive biomarkers from a randomized phase II study (POPLAR). Eur. J. Cancer, 51(Suppl. 3), 2015.
81. Higgs, B.W., Robbins, P.B., Blake-Haskins, J.A., Zhu, W., Morehouse, C., Brohawn, P.Z., et al. High tumoral IFNγ mRNA, PD-L1 protein, and combined IFNγ mRNA/PD-L1 protein expression associates with response to durvalumab (anti-PD-L1) monotherapy in NSCLC patients. Eur. J. Cancer, 51(Suppl. 3), 2015.
82. Midha, A., Walker, J., Rebelatto, M.C., Sabalos, C., Mistry, A., Schechter, N., The importance of quality standards to support test performance for the purpose of treatment decision making. Cancer Immunol. Res., 4(Suppl. 1), 2016, B004 (abstr).
83. Goldberg, S.B., Balmanoukian, A.S., Chaft, J., Rizvi, N.A., Sanborn, R.E., Rebelatto, M.C., et al. A phase 1b study to evaluate the safety and antitumor activity of MEDI4736 in combination with tremelimumab in patients with advanced NSCLC. Eur. J. Cancer, 51(Suppl. 3), 2015, S627.
84. Pinder, M.C., Rizvi, N.A., Goldberg, S.B., Balmanoukian, A.S., Narwal, R., Robbins, P.B., et al. A phase 1b open-label study to evaluate the safety and tolerability of MEDI4736, an anti–PD-L1 antibody, in combination with tremelimumab in subjects with advanced non–small cell lung cancer. J. Clin. Oncol., 32(Suppl. (15)), 2014, e19137 (abstr).
85. Gulley, J.L., Rajan, A., Spigel, D.R., Iannotti, N., Chandler, J., Wong, D.J., et al. Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with metastatic or recurrent non-small-cell lung cancer progressing after platinum-based chemotherapy: a phase Ib trial. Eur. J. Cancer, 51(Suppl. 3), 2015, S629.
86. Tokito, T., Azuma, M., Ishii, H., Yamada, K., Hoshino, T., Retrospective analysis between PD-L1 expression and prognosis for stage III non-small cell lung cancer patients who received concurrent chemoradiotherapy. J. Clin. Oncol., 33(Suppl. 15), 2015, 7542 (abstr).
87. Fitzmaurice, C., Dicker, D., Pain, A., Hamavid, H., Moradi-Lakeh, M., MacIntyre, M.F., et al. The global burden of cancer 2013. JAMA Oncol. 1:4 (2015), 505–527.
88. D'Incecco, A., Andreozzi, M., Ludovini, V., Rossi, E., Capodanno, A., Landi, L., et al. PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients. Br. J. Cancer 112:1 (2015), 95–102.
89. D'Incecco, A., Andreozzi, M., Ludovini, V., Rossi, E., Landi, L., Minuti, G., et al. PD- and PD-1 expression in molecularly selected non-small cell lung cancer (NSCLC) patients. J. Thorac. Oncol., 9(Suppl. 4), 2014.
90. Lin, C., Chen, X., Li, M., Liu, J., Qi, X., Yang, W., et al. Programmed death-ligand 1 expression predicts tyrosine kinase inhibitor response and better prognosis in a cohort of patients with epidermal growth factor receptor mutation-positive lung adenocarcinoma. Clin. Lung Cancer 16:5 (2015), e25–e35.
91. Chen, Y.B., Mu, C.Y., Huang, J.A., Clinical significance of programmed death-1 ligand-1 expression in patients with non-small cell lung cancer: a 5-year-follow-up study. Tumori 98:6 (2012), 751–755.
92. Chen, Y.-B., Mu, C.-Y., Huang, J.-A., Clinical significance of programmed death-1 ligand-1 expression in patients with non-small cell lung cancer: a 5-year-follow-up study. Respirology, 16(Suppl. 2), 2011, 163.
93. Rojas, L., Cardona, A.F., Arrieta, O., Carranza, H., Martín, C., Otero, J., et al. PD expression in metastatic non-small cell lung cancer patients from Colombia (CLICAP). J. Thorac. Oncol., 9(Suppl. 3 (9)), 2014, L1.
94. Sun, Y., Ye, H., Wu, H., O'Hara, C., PD-L1 expression in stage IV lung cancer. Lab. Invest., 94(S1), 2014.
95. Schalper, K.A., Velcheti, V., Carvajal-Hausdorf, D.E., Anagnostou, V., Syrigos, K., Gettinger, S., et al. Tumor infiltrating lymphocytes are associated with epithelial expression of PD-L1 protein, PD-L1 mRNA and better outcome in non-small cell lung cancer. Lab. Invest., 94(S1), 2014.
96. Velcheti, V., Schalper, K., Carvajal, D., Chen, L., Sznol, M., Gettinger, S.N., et al. Clinical significance of programmed death ligand-1 expression in non-small cell lung cancer NSCLC). J. Clin. Oncol., 31(Suppl. 15), 2013, 11075 (abstr).
97. Konishi, J., Yamazaki, K., Azuma, M., Kinoshita, I., Dosaka-Akita, H., Nishimura, M., B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression. Clin. Cancer Res. 10:15 (2004), 5094–5100.
98. Hellmann, M.D., Gettinger, S.N., Goldman, J.W., Brahmer, J.R., Borghaei, H., Chow, L.Q., et al. CheckMate 012: safety and efficacy of first-line (1L) nivolumab (nivo; N) and ipilimumab (ipi; I) in advanced (adv) NSCLC. J. Clin. Oncol., 34(Suppl), 2016, 3001 (abstr).
99. Sorensen, S.F., Zhou, W., Dolled-Filhart, M., Georgsen, J.B., Wang, Z., Emancipator, K., et al. PD-L1 expression and survival among patients with advanced non-small cell lung cancer treated with chemotherapy. Transl. Oncol. 9:1 (2016), 64–69.
100. 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 387:10030 (2016), 1837–1846.
101. Segal, N.H., Ou, S.-H., Balmanoukian, A., Fury, M., Massarelli, E., Brahmer, J., et al. Safety and efficacy of MEDI4736, an anti-PD-L1 antibody, in patients from a squamous cell carcinoma of the head and neck (SCCHN) expansion cohort. 2nd AstraZeneca-MedImmune Cambridge Cancer Science Symposium, Cambridge, UK, 20 September, 2015 (Abstract) 2015.
102. Borghaei, H., Brahmer, J.R., Horn, L., Ready, N., Steins, M., Felip, E., et al. Nivolumab (nivo) vs docetaxel (doc) in patients (pts) with advanced NSCLC: CheckMate 017/057 2-y update and exploratory cytokine profile analyses. J. Clin. Oncol., 34(Suppl), 2016, 9025 (abstr).
103. Pan, Z.K., Ye, F., Wu, X., An, H.X., Wu, J.X., Clinicopathological and prognostic significance of programmed cell death ligand1 (PD-L1) expression in patients with non-small cell lung cancer: a meta-analysis. J. Thoracic Dis. 7:3 (2015), 462–470.
104. Wang, A., Wang, H.Y., Liu, Y., Zhao, M.C., Zhang, H.J., Lu, Z.Y., et al. The prognostic value of PD-L1 expression for non-small cell lung cancer patients: a meta-analysis. Eur. J. Surg. Oncol. 41:4 (2015), 450–456.
105. Akbay, E.A., Koyama, S., Carretero, J., Altabef, A., Tchaicha, J.H., Christensen, C.L., et al. Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov. 3:12 (2013), 1355–1363.
106. Gainor, J.F., Shaw, A.T., Sequist, L.V., Fu, X., Azzoli, C.G., Piotrowska, Z., et al. EGFR mutations and ALK rearrangements are associated with low response rates to PD-1 pathway blockade in non-small cell lung cancer: a retrospective analysis. Clin. Cancer Res. 22:18 (2016), 4585–4593.
107. Hong, S., Chen, N., Fang, W., Zhan, J., Liu, Q., Kang, S., et al. Upregulation of PD-L1 by EML4-ALK fusion protein mediates the immune escape in ALK positive NSCLC: Implication for optional anti-PD-1/PD-L1 immune therapy for ALK-TKIs sensitive and resistant NSCLC patients. Oncoimmunology, 5(3), 2016, e1094598.
108. Ota, K., Azuma, K., Kawahara, A., Hattori, S., Iwama, E., Tanizaki, J., et al. Induction of PD-L1 expression by the EML4-ALK oncoprotein and downstream signaling pathways in non-small cell lung cancer. Clin. Cancer Res. 21:17 (2015), 4014–4021.
109. Zhou, Z.J., Zhan, P., Song, Y., PD-L1 over-expression and survival in patients with non-small cell lung cancer: a meta-analysis. Transl. Lung Cancer Res. 4:2 (2015), 203–208.
110. Huang, B., Chen, L., Bao, C., Sun, C., Li, J., Wang, L., et al. The expression status and prognostic significance of programmed cell death 1 ligand 1 in gastrointestinal tract cancer: a systematic review and meta-analysis. Onco Targets Ther. 8 (2015), 2617–2625.
111. Xu, F., Xu, L., Wang, Q., An, G., Feng, G., Liu, F., Clinicopathological and prognostic value of programmed death ligand-1 (PD-L1) in renal cell carcinoma: a meta-analysis. Int. J. Clin. Exp. Med. 8:9 (2015), 14595–14603.
112. Wu, P., Wu, D., Li, L., Chai, Y., Huang, J., PD-L1 and survival in solid tumors: a meta-analysis. PLoS One, 10(6), 2015, e0131403.
113. Herbst, R.S., Baas, P., Kim, D.W., Felip, E., Perez-Gracia, J.L., Han, J.Y., et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387:10027 (2016), 1540–1550.
114. Engel, K.B., Moore, H.M., Effects of preanalytical variables on the detection of proteins by immunohistochemistry in formalin-fixed, paraffin-embedded tissue. Arch. Pathol. Lab. Med. 135:5 (2011), 537–543.
115. Lin, F., Chen, Z., Standardization of diagnostic immunohistochemistry: literature review and geisinger experience. Arch. Pathol. Lab. Med. 138:12 (2014), 1564–1577.
116. D.B. Doroshow, R.B. Herbst. Pembrolizumab as first-line therapy in metastatic NSCLC: practice-changing implications of KEYNOTE-024 trial ASCO Post. 25 2016. Last accessed 10 January 20172016. Available from: http://www.ascopost.com/issues/november-25-2016/pembrolizumab-as-first-line-therapy-in-metastatic-nsclc-practice-changing-implications-of-keynote-024-trial/.
117. Deng, L., Liang, H., Burnette, B., Beckett, M., Darga, T., Weichselbaum, R.R., et al. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J. Clin. Invest. 124:2 (2014), 687–695.
118. Zhang, P., Su, D.M., Liang, M., Fu, J., Chemopreventive agents induce programmed death-1-ligand 1 (PD-L1) surface expression in breast cancer cells and promote PD-L1-mediated T cell apoptosis. Mol. Immunol. 45:5 (2008), 1470–1476.
119. Manson, G., Norwood, J., Marabelle, A., Kohrt, H., Houot, R., Biomarkers associated with checkpoint inhibitors. Ann. Oncol. 27:7 (2016), 1199–1206.
120. Ilie, M., Long-Mira, E., Bence, C., Butori, C., Lassalle, S., Bouhlel, L., 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. 27:1 (2016), 147–153.
121. Lizotte, P.H., Ivanova, E.V., Awad, M.M., Jones, R.E., Keogh, L., Liu, H., et al. Multiparametric profiling of non-small-cell lung cancers reveals distinct immunophenotypes. JCI Insight, 1(14), 2016, e89014.
122. Melosky, B., Chu, Q., Juergens, R., Leighl, N., McLeod, D., Hirsh, V., Pointed progress in second-line advanced non-small-cell lung cancer: the rapidly evolving field of checkpoint inhibition. J. Clin. Oncol. 34:14 (2016), 1676–1688.
123. Joshi, N.S., Akama-Garren, E.H., Lu, Y., Lee, D.Y., Chang, G.P., Li, A., et al. Regulatory T cells in tumor-associated tertiary lymphoid structures suppress anti-tumor T cell responses. Immunity 43:3 (2015), 579–590.