Skip to main content
View expanded cover

Targeted Therapies in Lung Cancer: Management Strategies for Nurses and Practitioners pp 65–84Cite as

The Impact and Toxicity of Checkpoint Inhibitors in Management of Lung Cancer

  • 350 Accesses

Abstract

Programmed death ligand-1/programmed death-1 checkpoint inhibitors have dramatically altered the treatment of advanced non-small cell lung cancer and significantly improved long-term survival for many patients. This chapter reviews their current achievements used alone, in combinations, or with radiation and discusses the management of their unique immune-related adverse effects.

Keywords

  • Immunotherapy
  • PD-1/PD-L1 inhibitor
  • Checkpoint inhibitor
  • Immune-related adverse events
  • Lung cancer

This is a preview of subscription content, access via your institution.

eBook
USD   19.99
Price excludes VAT (USA)
  • ISBN: 978-3-030-16550-5
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   29.99
Price excludes VAT (USA)
Hardcover Book
USD   29.99
Price excludes VAT (USA)
Learn about institutional subscriptions

References

  1. Puzanov I, Diab A, Abdallah K, Bingham CO, Brogdon C, Dadu R, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother Cancer. 2017;5(1):95.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  2. U.S Food and Drug Administration. Drugs@FDA: FDA approved drug products. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed 31 Jan 2019.

  3. Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018;378(22):2078–92.

    CAS  PubMed  CrossRef  Google Scholar 

  4. Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1–10.

    CrossRef  CAS  PubMed  Google Scholar 

  5. Pillai RN, Behera M, Owonikoko TK, Kamphorst AO, Pakkala S, Belani CP, et al. Comparison of the toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer: a systematic analysis of the literature. Cancer. 2018;124(2):271–7.

    CAS  PubMed  CrossRef  Google Scholar 

  6. Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823–33.

    CAS  CrossRef  PubMed  Google Scholar 

  7. Menzies A, Johnson D, Ramanujam S, Atkinson V, Wong A, Park J, et al. Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. Ann Oncol. 2016;28(2):368–76.

    Google Scholar 

  8. Haanen J, Carbonnel F, Robert C, Kerr KM, Peters S, Larkin J, et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl_4):iv119–iv42.

    CAS  PubMed  CrossRef  Google Scholar 

  9. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627–39.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  10. Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373(2):123–35.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  11. Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541(7637):321–30.

    CAS  PubMed  CrossRef  Google Scholar 

  12. Tsao M, Kerr K, Yatabe Y, Hirsch FR. PL 03.03 Blueprint 2: PD-L1 immunohistochemistry comparability study in real-life, clinical samples. J Thorac Oncol. 2017;12(11):S1606.

    CrossRef  Google Scholar 

  13. Hirsch FR, McElhinny A, Stanforth D, Ranger-Moore J, Jansson M, Kulangara K, et al. PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the Blueprint PD-L1 IHC assay comparison project. J Thorac Oncol. 2017;12(2):208–22.

    PubMed  CrossRef  Google Scholar 

  14. Takada K, Toyokawa G, Shoji F, Okamoto T, Maehara Y. The significance of the PD-L1 expression in non-small-cell lung cancer: trenchant double swords as predictive and prognostic markers. Clin Lung Cancer. 2018;19(2):120–9.

    CAS  PubMed  CrossRef  Google Scholar 

  15. National Comprehensive Cancer Network®. Management of Immunotherapy-related toxicities. Version 1. 2019. https://www.nccn.org/store/login/login.aspx?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf. Accessed 30 Jan 2018.

  16. Brahmer JR, Govindan R, Anders RA, Antonia SJ, Sagorsky S, Davies MJ, et al. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of non-small cell lung cancer (NSCLC). J Immunother Cancer. 2018;6(1):75.

    PubMed  PubMed Central  CrossRef  Google Scholar 

  17. Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018;36(17):1714–68.

    CAS  PubMed  CrossRef  Google Scholar 

  18. Besse B, Johnson M, Janne PA, Garassino M, Eberhardt WEE, Besse B, et al. 16LBA 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. 2015;51(Supplement 3):S717–S8.

    CrossRef  Google Scholar 

  19. Antonia SJ, Brahmer JR, Balmanoukian AS, Kim D-W, Kim S-W, Ahn M-J, et al. Safety and clinical activity of first-line durvalumab in advanced NSCLC: updated results from a Phase 1/2 study. J Clin Oncol. 2017;35(15_suppl):e20504.

    CrossRef  Google Scholar 

  20. Gettinger S, Rizvi NA, Chow LQ, Borghaei H, Brahmer J, Ready N, et al. Nivolumab monotherapy for first-line treatment of advanced non-small-cell lung cancer. J Clin Oncol. 2016;34(25):2980–7.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  21. Hui R, Garon EB, Goldman JW, Leighl NB, Hellmann MD, Patnaik A, et al. Pembrolizumab as first-line therapy for patients with PD-L1-positive advanced non-small cell lung cancer: a phase 1 trial. Ann Oncol. 2017;28(4):874–81.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  22. Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M, et al. First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. N Engl J Med. 2017;376(25):2415–26.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  23. Peters S, Antonia S, Goldberg SB, Heymach JV, Kim ES, Nakagawa K, et al. 191TiP: MYSTIC: a global, phase 3 study of durvalumab (MEDI4736) plus tremelimumab combination therapy or durvalumab monotherapy versus platinum-based chemotherapy (CT) in the first-line treatment of patients (pts) with advanced stage IV NSCLC. J Thorac Oncol. 2016;11(4 Suppl):S139–40.

    CrossRef  Google Scholar 

  24. Hanna N, Johnson D, Temin S, Baker S Jr, Brahmer J, Ellis PM, et al. Systemic therapy for stage IV non-small-cell lung cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2017;35(30):3484–515.

    CAS  PubMed  CrossRef  Google Scholar 

  25. National Comprehensive Cancer Network. Non-small cell lung cancer (version 3.2019). 2019. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed 29 Jan 2019.

  26. Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, 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;37(7):537–46.

    PubMed  CAS  CrossRef  Google Scholar 

  27. Gadgeel SM, Stevenson JP, Langer CJ, Gandhi L, Borghaei H, Patnaik A, et al. Pembrolizumab and platinum-based chemotherapy as first-line therapy for advanced non-small-cell lung cancer: phase 1 cohorts from the KEYNOTE-021 study. Lung Cancer. 2018;125:273–81.

    PubMed  CrossRef  Google Scholar 

  28. Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gumus M, Mazieres J, et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med. 2018;379(21):2040–51.

    CAS  PubMed  CrossRef  Google Scholar 

  29. Socinski MA, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018;378(24):2288–301.

    CAS  PubMed  CrossRef  Google Scholar 

  30. Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389(10066):255–65.

    PubMed  CrossRef  Google Scholar 

  31. Reck M. Pembrolizumab as first-line therapy for metastatic non-small-cell lung cancer. Immunotherapy. 2018;10(2):93–105.

    CAS  PubMed  CrossRef  Google Scholar 

  32. Brahmer JR, Rizvi NA, Lutzky J, Khleif S, Blake-Haskins A, Li X, et al. Clinical activity and biomarkers of MEDI4736, an anti-PD-L1 antibody, in patients with NSCLC. J Clin Oncol. 2014;32(15_suppl):8021.

    CrossRef  Google Scholar 

  33. Rizvi NA, Brahmer JR, Ou S-HI, Segal NH, 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. 2015;33(15_suppl):8032.

    CrossRef  Google Scholar 

  34. Herbst RS, Baas P, Kim DW, Felip E, Perez-Gracia JL, Han JY, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540–50.

    CAS  PubMed  CrossRef  Google Scholar 

  35. Fehrenbacher L, von Pawel J, Park K, Rittmeyer A, Gandara DR, Ponce Aix S, et al. Updated efficacy analysis including secondary population results for OAK: a randomized phase III study of atezolizumab versus docetaxel in patients with previously treated advanced non-small cell lung cancer. J Thorac Oncol. 2018;13(8):1156–70.

    PubMed  CrossRef  Google Scholar 

  36. Horn L, Spigel DR, Vokes EE, Holgado E, Ready N, Steins M, et al. Nivolumab versus docetaxel in previously treated patients with advanced non-small-cell lung cancer: two-year outcomes from two randomized, open-label, phase III trials (CheckMate 017 and CheckMate 057). J Clin Oncol. 2017;35(35):3924–33.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  37. Vokes EE, Ready N, Felip E, Horn L, Burgio MA, Antonia SJ, et al. Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases. Ann Oncol. 2018;29(4):959–65.

    CAS  PubMed  CrossRef  Google Scholar 

  38. Reck M, Coon C, Taylor F, DeRosa M, Penrod J, Dastani H, et al. 3011 Evaluation of overall health status in patients with advanced squamous non-small cell lung cancer treated with nivolumab or docetaxel in CheckMate 017. Eur J Cancer. 2015;51:S599–600.

    CrossRef  Google Scholar 

  39. Gralla R, Coon C, Taylor F, Penrod J, DeRosa M, Dastani H, et al., editors. Evaluation of disease-related symptoms in patients (pts) with advanced squamous (SQ) non-small cell lung cancer (NSCLC) treated with nivolumab (NIVO) or docetaxel (DOC). Basel, Switzerland: Oncology Research and Treatment; 2015.

    Google Scholar 

  40. Passiglia F, Galvano A, Rizzo S, Incorvaia L, Listi A, Bazan V, et al. Looking for the best immune-checkpoint inhibitor in pre-treated NSCLC patients: an indirect comparison between nivolumab, pembrolizumab and atezolizumab. Int J Cancer. 2018;142(6):1277–84.

    CAS  PubMed  CrossRef  Google Scholar 

  41. Spigel D, McLeod M, Hussein M, Waterhouse D, Einhorn L, Horn L, et al. 1297ORandomized results of fixed-duration (1-yr) vs continuous nivolumab in patients (pts) with advanced non-small cell lung cancer (NSCLC). Ann Oncol. 2017;28(suppl_5):v460–v496.

    Google Scholar 

  42. Davies M. New modalities of cancer treatment for NSCLC: focus on immunotherapy. Cancer Manag Res. 2014;6:63–75.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  43. Gubens MA, Sequist LV, Stevenson J, Powell SF, Villaruz LC, Gadgeel SM, et al. Phase I/II study of pembrolizumab (pembro) plus ipilimumab (ipi) as second-line therapy for NSCLC: KEYNOTE-021 cohorts D and H. J Clin Oncol. 2016;34(15_suppl):9027.

    CrossRef  Google Scholar 

  44. Hellmann MD, Rizvi NA, Goldman JW, Gettinger SN, Borghaei H, Brahmer JR, 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;18(1):31–41.

    CAS  PubMed  CrossRef  Google Scholar 

  45. Tanvetyanon T, Gray JE, Antonia SJ. PD-1 checkpoint blockade alone or combined PD-1 and CTLA-4 blockade as immunotherapy for lung cancer? Expert Opin Biol Ther. 2017;17(3):305–12.

    CAS  PubMed  CrossRef  Google Scholar 

  46. Schadendorf D, Wolchok JD, Hodi FS, Chiarion-Sileni V, Gonzalez R, Rutkowski P, et al. Efficacy and safety outcomes in patients with advanced melanoma who discontinued treatment with nivolumab and ipilimumab because of adverse events: a pooled analysis of randomized phase II and III trials. J Clin Oncol. 2017;35(34):3807–14.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  47. Meng X, Liu Y, Zhang J, Teng F, Xing L, Yu J. PD-1/PD-L1 checkpoint blockades in non-small cell lung cancer: new development and challenges. Cancer Lett. 2017;405:29–37.

    CAS  PubMed  CrossRef  Google Scholar 

  48. Herter-Sprie GS, Koyama S, Korideck H, Hai J, Deng J, Li YY, et al. Synergy of radiotherapy and PD-1 blockade in Kras-mutant lung cancer. JCI Insight. 2016;1(9):e87415.

    PubMed  PubMed Central  CrossRef  Google Scholar 

  49. Gong X, Li X, Jiang T, Xie H, Zhu Z, Zhou F, et al. Combined radiotherapy and anti-PD-L1 antibody synergistically enhances antitumor effect in non-small cell lung cancer. J Thorac Oncol. 2017;12(7):1085–97.

    PubMed  CrossRef  Google Scholar 

  50. Qiao M, Jiang T, Ren S, Zhou C. Combination strategies on the basis of immune checkpoint inhibitors in non-small-cell lung cancer: where do we stand? Clin Lung Cancer. 2018;19(1):1–11.

    CAS  PubMed  CrossRef  Google Scholar 

  51. Takamori S, Toyokawa G, Takada K, Shoji F, Okamoto T, Maehara Y. Combination therapy of radiotherapy and anti-PD-1/PD-L1 treatment in non-small-cell lung cancer: a mini-review. Clin Lung Cancer. 2018;19(1):12–6.

    CAS  PubMed  CrossRef  Google Scholar 

  52. Gerber DE, Urbanic JJ, Langer C, Hu C, Chang IF, Lu B, et al. Treatment design and rationale for a randomized trial of cisplatin and etoposide plus thoracic radiotherapy followed by nivolumab or placebo for locally advanced non-small-cell lung cancer (RTOG 3505). Clin Lung Cancer. 2017;18(3):333–9.

    CAS  PubMed  CrossRef  Google Scholar 

  53. Shaverdian N, Lisberg AE, Bornazyan K, Veruttipong D, Goldman JW, Formenti SC, et al. Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial. Lancet Oncol. 2017;18(7):895–903.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  54. Bledsoe TJ, Rutter CE, Lester-Coll NH, Bi X, Decker RH. Radiation to oligoprogessive sites of disease can prolong the duration of response to immune checkpoint inhibitors in patients with metastatic non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 2016;96(2):E479.

    CrossRef  Google Scholar 

  55. Ahmed KA, Kim S, Arrington J, Naghavi AO, Dilling TJ, Creelan BC, et al. Outcomes targeting the PD-1/PD-L1 axis in conjunction with stereotactic radiation for patients with non-small cell lung cancer brain metastases. J Neuro-Oncol. 2017;133(2):331–8.

    CAS  CrossRef  Google Scholar 

  56. Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018;379(24):2342–50.

    CAS  PubMed  CrossRef  Google Scholar 

  57. Hui R, Özgüroğlu M, Daniel D, Baz D, Murakami S, Yokoi T, et al. PL 02.02 patient-reported outcomes with durvalumab after chemoradiation in locally advanced, unresectable NSCLC: data from PACIFIC. J Thorac Oncol. 2017;12(11):S1604.

    CrossRef  Google Scholar 

  58. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Non-Small Cell Lung Cancer Version 4.2019. 2017. https://www.nccn.org/store/login/login.aspx?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed 12 May 2019.

  59. Ott PA, Elez E, Hiret S, Kim DW, Morosky A, Saraf S, et al. Pembrolizumab in patients with extensive-stage small-cell lung cancer: results from the phase Ib KEYNOTE-028 study. J Clin Oncol. 2017;35(34):3823–9.

    CAS  PubMed  CrossRef  Google Scholar 

  60. Antonia SJ, Lopez-Martin JA, Bendell J, Ott PA, Taylor M, Eder JP, 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;17(7):883–95.

    CAS  PubMed  CrossRef  Google Scholar 

  61. Rizvi N, Antonia S, Callahan MK, Awad MM, Calvo E, Ascierto PA, et al. Abstract OA 07.03a: impact of tumor mutation burden on the efficacy of nivolumab or Nivolumab + Ipilimumab in small cell lung cancer: an exploratory analysis of CheckMate 032. Presented at the IASLC 18th world conference on lung cancer, 15–18 October, Yokohama, Japan. International Association For the Study of Lung Cancer; 2017.

    Google Scholar 

  62. Reck M, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, et al. Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol. 2013;24(1):75–83.

    CAS  PubMed  CrossRef  Google Scholar 

  63. Horn L, Mansfield AS, Szczęsna A, Havel L, Krzakowski M, Hochmair MJ, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018;379(23):2220–9.

    CAS  PubMed  CrossRef  Google Scholar 

  64. Alley EW, Lopez J, Santoro A, Morosky A, Saraf S, Piperdi B, et al. Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. Lancet Oncol. 2017;18(5):623–30.

    CAS  PubMed  CrossRef  Google Scholar 

  65. Zalcman G, Mazieres J, Greillier L, Lantuejoul S, Dô P, Bylicki O, et al. LBA58_PRSecond or 3rd line nivolumab (Nivo) versus nivo plus ipilimumab (Ipi) in malignant pleural mesothelioma (MPM) patients: updated results of the IFCT-1501 MAPS2 randomized phase 2 trial. Ann Oncol. 2017;28(suppl_5):v605–v649.

    Google Scholar 

  66. Sato K, Akamatsu H, Murakami E, Sasaki S, Kanai K, Hayata A, et al. Correlation between immune-related adverse events and efficacy in non-small cell lung cancer treated with nivolumab. Lung Cancer. 2018;115:71–4.

    PubMed  CrossRef  Google Scholar 

  67. Teraoka S, Fujimoto D, Morimoto T, Kawachi H, Ito M, Sato Y, et al. Early immune-related adverse events and association with outcome in advanced non–small cell lung cancer patients treated with nivolumab: a prospective cohort study. J Thorac Oncol. 2017;12(12):1798–805.

    PubMed  CrossRef  Google Scholar 

  68. Haratani K, Hayashi H, Chiba Y, Kudo K, Yonesaka K, Kato R, et al. Association of immune-related adverse events with nivolumab efficacy in non-small-cell lung cancer. JAMA Oncol. 2018;4(3):374–8.

    PubMed  CrossRef  Google Scholar 

  69. O’Kane GM, Labbe C, Doherty MK, Young K, Albaba H, Leighl NB. Monitoring and management of immune-related adverse events associated with programmed cell death protein-1 axis inhibitors in lung cancer. Oncologist. 2017;22(1):70–80.

    PubMed  CrossRef  CAS  Google Scholar 

  70. Nishijima TF, Shachar SS, Nyrop KA, Muss HB. Safety and tolerability of PD-1/PD-L1 inhibitors compared with chemotherapy in patients with advanced cancer: a meta-analysis. Oncologist. 2017;22(4):470–9.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  71. Inoue T, Tamiya M, Tamiya A, Nakahama K, Taniguchi Y, Shiroyama T, et al. Analysis of early death in Japanese patients with advanced non-small-cell lung cancer treated with nivolumab. Clin Lung Cancer. 2018;19(2):e171–e6.

    CAS  PubMed  CrossRef  Google Scholar 

  72. Villadolid J, Amin A. Immune checkpoint inhibitors in clinical practice: update on management of immune-related toxicities. Transl Lung Cancer Res. 2015;4(5):560–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. U.S. Department of Health and Human Services. Common terminology criteria for adverse events (CTCAE). Version 4.0. Published: 28 May 2009 (v4.03: 14 June 2010). https://www.eortc.be/services/doc/ctc/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf. Accessed 5 Feb 2019.

  74. U.S. Department of Health and Human Services. Common terminology criteria for adverse events (CTCAE). Version 5.0. Published: November 27, 2017. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_8.5x11.pdf.

  75. Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2017;377(20):1919–29.

    CAS  PubMed  CrossRef  Google Scholar 

  76. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–28.

    CrossRef  Google Scholar 

  77. Chmiel KD, Suan D, Liddle C, Nankivell B, Ibrahim R, Bautista C, et al. Resolution of severe ipilimumab-induced hepatitis after antithymocyte globulin therapy. J Clin Oncol. 2011;29(9):e237–40.

    CAS  PubMed  CrossRef  Google Scholar 

  78. Gandara DR, Kowanetz M, Mok TSK, Rittmeyer A, Fehrenbacher L, Fabrizio D, et al. 1295OBlood-based biomarkers for cancer immunotherapy: tumor mutational burden in blood (bTMB) is associated with improved atezolizumab (atezo) efficacy in 2L+ NSCLC (POPLAR and OAK). Ann Oncol. 2017;28(suppl_5):mdx380-mdx.

    CrossRef  Google Scholar 

  79. Leger PD, Rothschild S, Castellanos E, Pillai RN, York SJ, Horn L. Response to salvage chemotherapy following exposure to immune checkpoint inhibitors in patients with non-small cell lung cancer. J Clin Oncol. 2017;35:9084.

    CrossRef  Google Scholar 

  80. Brahmer JR, Rodriguez-Abreu D, Robinson AG, Hui R, Csõszi T, Fülöp A, et al. Progression after the next line of therapy (PFS2) and updated OS among patients (pts) with advanced NSCLC and PD-L1 tumor proportion score (TPS)≥ 50% enrolled in KEYNOTE-024. J Clin Oncol. 2017;35(15_suppl):abstr 9000.

    CrossRef  Google Scholar 

  81. Park SE, Lee SH, Ahn JS, Ahn M-J, Park K, Sun J-M. Increased response rates to salvage chemotherapy administered after PD-1/PD-L1 inhibitors in patients with non-small cell lung cancer. J Thorac Oncol. 2018;13(1):106–11.

    PubMed  CAS  CrossRef  Google Scholar 

  82. Grigg C, Reuland BD, Sacher AG, Yeh R, Rizvi NA, Shu CA. Clinical outcomes of patients with non-small cell lung cancer (NSCLC) receiving chemotherapy after immune checkpoint blockade. J Clin Oncol. 2017;35(15_suppl):9082.

    CrossRef  Google Scholar 

  83. Vasson M, Filaire E, Bernalier-Donadille A, Bingula R, Filaire M. Microbiota and the lung cancer (MICA). NCT03068663 (2016-A01640-51). 2017. https://clinicaltrials.gov/ct2/show/NCT03068663.

  84. Janne PA, Syndax Pharmaceuticals, Merck Sharp & Dohme Corp. Ph1b/2 Dose-escalation study of entinostat with pembrolizumab in NSCLC with expansion cohorts in NSCLC, melanoma, and colorectal cancer. NCT02437136 (SNDX-275-0601). 2017. https://clinicaltrials.gov/ct2/show/NCT02437136.

  85. Jones M, Incyte Corporation, Merck Sharp & Dohme Corp. A Phase 1/2 study exploring the safety, tolerability, and efficacy of pembrolizumab (MK-3475) in combination with epacadostat (INCB024360) in subjects with selected cancers (INCB 24360-202/MK-3475-037/KEYNOTE-037/ ECHO-202). NCT02178722. 2017. https://clinicaltrials.gov/ct2/show/NCT02178722.

  86. Meric-Bernstam F, Gordon M, Tykodi S, Lam E, Vaishampayan U, Chaves J, et al. Abstract O16: a phase 1/2 study of CB-839, a first in class glutaminase inhibitor, combined with nivolumab inpatients with advanced melanoma (MEL), renal cell carcinoma (RCC), or non-small cell lung cancer (NSCLC). Presented at the 32nd annual meeting and pre-conference programs of the Society for Immunotherapy of Cancer (SITC 2017): Part One National Harbor, MD, USA. 8–12 November 2017. Abstracts. Journal for immunotherapy of cancer. 2017;5.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Stephanie Crawford Andrews

  2. Yale Comprehensive Cancer Center, Yale University School of Nursing, New Haven, CT, USA

    Marianne Davies

Authors
  1. Stephanie Crawford Andrews
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marianne Davies
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stephanie Crawford Andrews .

Editor information

Editors and Affiliations

  1. Yale Comprehensive Cancer Center, Yale University School of Nursing, New Haven, CT, USA

    Dr. Marianne Davies

  2. Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA

    Beth Eaby-Sandy

Rights and permissions

Reprints and Permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Verify currency and authenticity via CrossMark

Cite this chapter

Andrews, S.C., Davies, M. (2019). The Impact and Toxicity of Checkpoint Inhibitors in Management of Lung Cancer. In: Davies, M., Eaby-Sandy, B. (eds) Targeted Therapies in Lung Cancer: Management Strategies for Nurses and Practitioners. Springer, Cham. https://doi.org/10.1007/978-3-030-16550-5_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-16550-5_7

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-16549-9

  • Online ISBN: 978-3-030-16550-5

  • eBook Packages: MedicineMedicine (R0)