1,734
Views
4
CrossRef citations to date
0
Altmetric
Review Article

Immune checkpoint inhibitors of the PD-1/PD-L1-axis in non-small cell lung cancer: promise, controversies and ambiguities in the novel treatment paradigm

, , &
Pages 360-369 | Received 06 Dec 2019, Accepted 10 Mar 2020, Published online: 02 Apr 2020

References

  • Brody R, Zhang Y, Ballas M, et al. PD-L1 expression in advanced NSCLC: insights into risk stratification and treatment selection from a systematic literature review. Lung Cancer. 2017;112:200–215.
  • 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;35(34):3867–3876.
  • Lantuejoul S, Sound-Tsao M, Cooper WA, et al. Perspective from the IASLC pathology committee. J Thorac Oncol. 2019. doi:10.1016/j.jtho.2019.12.107 [Online ahead of print]
  • Teixido C, Vilarino N, Reyes R, et al. PD-L1 expression testing in non-small cell lung cancer. Ther Adv Med Oncol. 2018;10:1758835918763493.
  • World Health Organization. Global cancer observatory: international agency for research on cancer. 2018. [cited 2019 Nov 13]. Available from: http://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf
  • Socialstyrelsen. Cancer i siffror 2018 Stockholm: socialstyrelsen. 2018. [cited 2020 Feb 19]. Available from: https://static-files.cancerfonden.se/Cancer_i_siffror_2018online_webb.pdf
  • Arnold M, Rutherford MJ, Bardot A, et al. Progress in cancer survival, mortality, and incidence in seven high-income countries 1995–2014 (ICBP SURVMARK-2): a population-based study. Lancet Oncol. 2019;20(11):1493–1505.
  • 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;37(28):2518–2527.
  • 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;37(7):537–546.
  • 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;393(10183):1819–1830.
  • Hellmann MD, Paz-Ares L, Bernabe Caro R, et al. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. N Engl J Med. 2019;381(21):2020–2031.
  • 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;376(25):2415–2426.
  • 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;378(22):2093–2104.
  • Aguilar EJ, Ricciuti B, Gainor JF, et al. Outcomes to first-line pembrolizumab in patients with non-small cell lung cancer and very high PD-L1 expression. Ann Oncol. 2019;30(10):1653–1659.
  • Barlesi F, Vansteenkiste J, Spigel D, et al. Avelumab versus docetaxel in patients with platinum-treated advanced non-small-cell lung cancer (JAVELIN Lung 200): an open-label, randomised, phase 3 study. Lancet Oncol. 2018;19(11):1468–1479.
  • Chen R, Hou X, Yang L, et al. Comparative efficacy and safety of first-line treatments for advanced non-small cell lung cancer with immune checkpoint inhibitors: a systematic review and meta-analysis. Thorac Cancer. 2019;10(4):607–623.
  • Dafni U, Tsourti Z, Vervita K, et al. Immune checkpoint inhibitors, alone or in combination with chemotherapy, as first-line treatment for advanced non-small cell lung cancer. A systematic review and network meta-analysis. Lung Cancer. 2019;134:127–140.
  • Tun AM, Thein KZ, Thein WL, et al. Checkpoint inhibitors plus chemotherapy for first-line treatment of advanced non-small cell lung cancer: a systematic review and meta-analysis of randomized controlled trials. Future Sci OA. 2019;5(9):FSO421.
  • Shen X, Zhao B. Efficacy of PD-1 or PD-L1 inhibitors and PD-L1 expression status in cancer: meta-analysis. BMJ. 2018;362:k3529.
  • Catenacci DVT, Hochster H, Klempner SJ. Keeping checkpoint inhibitors in check. JAMA Netw Open. 2019;2(5):e192546–e192546.
  • Gill J, Prasad V. A reality check of the accelerated approval of immune-checkpoint inhibitors. Nat Rev Clin Oncol. 2019;16(11):656–658.
  • Haslam A, Prasad V. Estimation of the percentage of US patients with cancer who are eligible for and respond to checkpoint inhibitor immunotherapy drugs. JAMA Netw Open. 2019;2(5):e192535–e192535.
  • Pons-Tostivint E, Latouche A, Vaflard P, et al. Comparative analysis of durable responses on immune checkpoint inhibitors versus other systemic therapies: a pooled analysis of phase III trials. JCO Precis Oncol. 2019;(3):1–10. doi:10.1200/PO.18.00114
  • Bartlett VL, Dhruva SS, Shah ND, et al. Feasibility of using real-world data to replicate clinical trial evidence. JAMA Netw Open. 2019;2(10):e1912869.
  • Moran M, Nickens D, Adcock K, et al. Augmenting the randomized controlled trial with real-world data to aid clinical decision making in metastatic renal cell carcinoma: a systematic review and meta-analysis. Future Oncol. 2019;15(34):3987–4001.
  • Pillai RN, Behera M, Owonikoko TK, 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):271–277.
  • Petri CR, Patell R, Batalini F, et al. Severe pulmonary toxicity from immune checkpoint inhibitor treated successfully with intravenous immunoglobulin: case report and review of the literature. Resp Med Case Rep. 2019;27:100834.
  • Zhang D, Zhang Y, Huang Y, et al. Hyper-progressive disease in a patient with advanced non-small cell lung cancer on immune checkpoint inhibitor therapy: a case report and literature review. Lung Cancer. 2020;139:18–21.
  • Lisberg A, Tucker DA, Goldman JW, et al. Treatment-related adverse events predict improved clinical outcome in NSCLC patients on KEYNOTE-001 at a single center. Cancer Immunol Res. 2018;6(3):288–294.
  • Lantuejoul S, Adam J, Girard N, et al. PD-L1 testing in non-small cell lung carcinoma: guidelines from the PATTERN group of thoracic pathologists. Annal Pathol. 2018;38(2):110–125.
  • Sica GL, Ramalingam SS. Assays for PD-L1 expression: do all roads lead to Rome? JAMA Oncol. 2017;3(8):1058–1059.
  • Torlakovic E, Lim HJ, Adam J, et al. Interchangeability of PD-L1 immunohistochemistry assays: a meta-analysis of diagnostic accuracy. Mod Pathol. 2020;33(1):4–17.
  • Mino-Kenudsen M, Lantuejoul S. Global survey for pathologists on PD-L1 testing: moving towards standardization. 2019. [cited 2020 Feb 20]. Available from: Lungcancernews.org
  • Batenchuk C, Albitar M, Zerba K, et al. A real-world, comparative study of FDA-approved diagnostic assays PD-L1 IHC 28-8 and 22C3 in lung cancer and other malignancies. J Clin Pathol. 2018;71(12):1078–1083.
  • Brunnstrom H, Johansson A, Westbom-Fremer S, et al. PD-L1 immunohistochemistry in clinical diagnostics of lung cancer: inter-pathologist variability is higher than assay variability. Mod Pathol. 2017;30(10):1411–1421.
  • Casadevall D, Clave S, Taus A, et al. Heterogeneity of tumor and immune cell PD-L1 expression and lymphocyte counts in surgical NSCLC samples. Clin Lung Cancer. 2017;18(6):682–691.e5.
  • Chan AWH, Tong JHM, Kwan JSH, et al. Assessment of programmed cell death ligand-1 expression by 4 diagnostic assays and its clinicopathological correlation in a large cohort of surgical resected non-small cell lung carcinoma. Mod Pathol. 2018;31(9):1381–1390.
  • 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;12(2):208–222.
  • Marchetti A, Barberis M, Franco R, et al. Multicenter comparison of 22C3 pharmDx (agilent) and SP263 (ventana) assays to Test PD-L1 expression for NSCLC patients to be treated with immune checkpoint inhibitors. J Thorac Oncol. 2017;12(11):1654–1663.
  • Rimm DL, Han G, Taube JM, et al. A Prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small cell lung cancer. JAMA Oncol. 2017;3(8):1051–1058.
  • Scheel AH, Baenfer G, Baretton G, et al. Interlaboratory concordance of PD-L1 immunohistochemistry for non-small-cell lung cancer. Histopathology. 2018;72(3):449–459.
  • Tsao MS, Kerr KM, Kockx M, et al. PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of blueprint phase 2 project. J Thorac Oncol. 2018;13(9):1302–1311.
  • Yeo MK, Choi SY, Seong IO, et al. Association of PD-L1 expression and PD-L1 gene polymorphism with poor prognosis in lung adenocarcinoma and squamous cell carcinoma. Hum Pathol. 2017;68:103–111.
  • Munari E, Zamboni G, Lunardi G, et al. PD-L1 expression in non-small cell lung cancer: evaluation of the diagnostic accuracy of a laboratory-developed test using clone E1L3N in comparison with 22C3 and SP263 assays. Hum Pathol. 2019;90:54–59.
  • Ilie M, Khambata-Ford S, Copie-Bergman C, et al. Use of the 22C3 anti-PD-L1 antibody to determine PD-L1 expression in multiple automated immunohistochemistry platforms. PLoS One. 2017;12(8):e0183023.
  • Hendry S, Byrne DJ, Wright GM, et al. Comparison of four PD-L1 immunohistochemical assays in lung cancer. J Thorac Oncol. 2018;13(3):367–376.
  • Williams GH, Nicholson AG, Snead DRJ, et al. Interobserver reliability of programmed cell death ligand-1 scoring using the VENTANA PD-L1 (SP263) assay in NSCLC. J Thorac Oncol. 2019. doi: 1016/j.jtho.2019.11.010 2019 Nov 25 [Online ahead of print]
  • Elfving H, Mattsson JSM, Lindskog C, et al. Programmed cell death ligand 1 immunohistochemistry: a concordance study between surgical specimen, biopsy, and tissue microarray. Clin Lung Cancer. 2019;20(4):258–262 e1.
  • 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;27(1):147–153.
  • Kitazono S, Fujiwara Y, Tsuta K, et al. Reliability of small biopsy samples compared with resected specimens for the determination of programmed death-ligand 1 expression in non–small-cell lung cancer. Clin Lung Cancer. 2015;16(5):385–390.
  • Regionala Cancercentrum i Samverkan. Lungcancer nationellt vårdprogram. 2019. [cited 2020 Feb 20]. Available from: https://kunskapsbanken.cancercentrum.se/diagnoser/lungcancer/vardprogram/
  • Robinson M, James J, Thomas G, et al. Quality assurance guidance for scoring and reporting for pathologists and laboratories undertaking clinical trial work. J Pathol Clin Res. 2019;5(2):91–99.
  • Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823–1833.
  • Aguiar PN, Jr., Perry LA, Penny-Dimri J, et al. The effect of PD-L1 testing on the cost-effectiveness and economic impact of immune checkpoint inhibitors for the second-line treatment of NSCLC. Ann Oncol. 2017;28(9):2256–2263.
  • Chabrol Haas L, Coutinho MB, Peixoto RB, et al. Use of PD-L1 biomarker in second line therapy for non-small cell lung cancer: budget impact analysis from a private payer perspective in Brazil. Value Health. 2018;21:S23.
  • Chouaid C, Bensimon L, Clay E, et al. Cost-effectiveness analysis of pembrolizumab versus standard-of-care chemotherapy for first-line treatment of PD-L1 positive (>50%) metastatic squamous and non-squamous non-small cell lung cancer in France. Lung Cancer. 2019;127:44–52.
  • Criss SD, Mooradian MJ, Watson TR, et al. Cost-effectiveness of atezolizumab combination therapy for first-line treatment of metastatic nonsquamous non-small cell lung cancer in the United States. JAMA Netw Open. 2019;2(9):e1911952.
  • Gao L, Li SC. Modelled economic evaluation of nivolumab for the treatment of second-line advanced or metastatic squamous non-small-cell lung cancer in Australia using both partition survival and markov models. Appl Health Econ Health Policy. 2019;17(3):371–380.
  • Georgieva M, da Silveira Nogueira Lima JP, Aguiar P Jr, et al. Cost-effectiveness of pembrolizumab as first-line therapy for advanced non-small cell lung cancer. Lung Cancer. 2018;124:248–254.
  • Loong HH, Wong CKH, Leung LKS, et al. Cost effectiveness of PD-L1-based test-and-treat strategy with pembrolizumab as the first-line treatment for metastatic NSCLC in Hong Kong. Pharmacoecon Open. 2019. doi:10.1007/s41669-019-00178-7 [Online ahead of print].
  • Matter-Walstra K, Schwenkglenks M, Aebi S, et al. A cost-effectiveness analysis of nivolumab versus docetaxel for advanced nonsquamous NSCLC including PD-L1 testing. J Thorac Oncol. 2016;11(11):1846–1855.
  • She L, Hu H, Liao M, et al. Cost-effectiveness analysis of pembrolizumab versus chemotherapy as first-line treatment in locally advanced or metastatic non-small cell lung cancer with PD-L1 tumor proportion score 1% or greater. Lung Cancer. 2019;138:88–94.
  • Zhou K, Jiang C, Li Q. Cost-effectiveness analysis of pembrolizumab monotherapy and chemotherapy in the non-small-cell lung cancer with different PD-L1 tumor proportion scores. Lung Cancer. 2019;136:98–101.
  • Agilent Technologies Inc. PD-L1 IHC 22C3 pharmDx interpretation manual - NSCLC. Santa Clara (CA): Agilent Technologies Inc; 2018.
  • National Institute for Health and Care Excellence (NICE). Single technology appraisal: pembrolizumab for treating PD-L1-positive non-small-cell lung cancer after platinumbased chemotherapy [ID840] – committee papers. London: National Institute for Health and Care Excellence (NICE); 2016.
  • National Institute for Health and Care Excellence (NICE). Single technology appraisal: atezolizumab for treating non-small-cell lung cancer after platinum-based chemotherapy [ID970] – committee papers. London: National Institute for Health and Care Excellence (NICE); 2018.
  • Imfinzi (durvalumab) Stockholm: tandvårds- och läkemedelsförmånsverket (TLV). 2018. [cited 2020 Feb 20]. Available from: https://www.tlv.se/download/18.13634819166e2df86244c71e/1541598097880/bes_underlag181106_imfinzi.pdf
  • National Institute for Health and Care Excellence (NICE). Nivolumab for previously treated squamous non-small cell lung cancer technology appraisal guidance [TA483]. London: National Institute for Health and Care Excellence (NICE); 2017.
  • National Institute for Health and Care Excellence (NICE). Final appraisal determination Nivolumab for previously treated nonsquamous non-small-cell lung cancer. London: National Institute for Health and Care Excellence (NICE); 2017.
  • National Institute for Health and Care Excellence (NICE). Pembrolizumab for untreated PD-L1 positive metastatic non-small-cell lung cancer (CDF review of TA447) [ID1349]. London: National Institute for Health and Care Excellence (NICE); 2018.
  • National Institute for Health and Care Excellence (NICE). Atezolizumab for treating locally advanced or metastatic non-small-cell lung cancer after chemotherapy. London: National Institute for Health and Care Excellence (NICE); 2018.
  • Tandvårds- och läkemedelsförmånsverket (TLV). Keytruda (pembrolizumab) Stockholm: tandvårds- och läkemedelsförmånsverket (TLV). 2017. [cited 2020 Feb 20]. Available from: https://www.tlv.se/download/18.467926b615d084471ac338ea/1510316399554/Kunskapsunderlag_keytruda_forsta_linjen_icke_smacellig_lungcancer.pdf
  • Tandvårds- och Läkemedelsförmånsverket (TLV). Tecentriq (atezolizumab) Stockholm: tandvårds- och läkemedelsförmånsverket (TLV). 2018. [cited 2020 Feb 20]. Available from: https://www.tlv.se/download/18.564d7770164e1dcb5d6a230c/1533290942740/bes180123_underlag_tecentriq.pdf
  • Tandvårds- och läkemedelsförmånsverket (TLV). Opdivo (nivolumab) Stockholm: tandvårds- och läkemedelsförmånsverket (TLV). 2015. [cited 2020 Feb 20]. Available from: https://www.tlv.se/download/18.467926b615d084471ac33ab9/1510316360481/Kunskapsunderlag_opdivo_lungcancer.pdf
  • Linden S, Redig J, Banos Hernaez A, et al. Comorbidities and relevant outcomes, commonly associated with cancer, of patients newly diagnosed with advanced non-small-cell lung cancer in Sweden. Eur J Cancer Care (Engl). 2019;29:e13171.
  • Pearce A, Haas M, Viney R. Are the true impacts of adverse events considered in economic models of antineoplastic drugs? A systematic review. Appl Health Econ Health Policy. 2013;11(6):619–637.
  • Wood R, Taylor-Stokes G, Smith F, et al. The humanistic burden of advanced non-small cell lung cancer (NSCLC) in Europe: a real-world survey linking patient clinical factors to patient and caregiver burden. Qual Life Res. 2019;28(7):1849–1861.
  • Restelli U, Artale S, Pacelli V, et al. Financial consequences of the performance of A Pd-L1 test to select patients receiving second and third line treatments for non-small cell lung cancer in Italy. Value Health. 2017;20(9):A424.
  • Sheppard B, Ahlsten M, Paolini D, et al. The budget impact of introducing A PD-L1 assay to select patients with metastatic nsclc who are potential candidates for treatment with immune checkpoint inhibitors. Value Health. 2017;20(9):A576.
  • Friedlaender A, Addeo A, Banna G. New emerging targets in cancer immunotherapy: the role of TIM3. ESMO Open. 2019;4(3):e000497.
  • Puhr HC, Ilhan-Mutlu A. New emerging targets in cancer immunotherapy: the role of LAG3. ESMO Open. 2019;4(2):e000482.
  • Bruno TC. New predictors for immunotherapy responses sharpen our view of the tumour microenvironment. Nature. 2020;577(7791):474–476.
  • Cabrita R, Lauss M, Sanna A, et al. Tertiary lymphoid structures improve immunotherapy and survival in melanoma. Nature. 2020;577(7791):561–565.
  • Helmink BA, Reddy SM, Gao J, et al. B cells and tertiary lymphoid structures promote immunotherapy response. Nature. 2020;577(7791):549–555.
  • Petitprez F, de Reynies A, Keung EZ, et al. B cells are associated with survival and immunotherapy response in sarcoma. Nature. 2020;577(7791):556–560.
  • Kim H, Chung JH. PD-L1 testing in non-small cell lung cancer: past, present, and future. J Pathol Transl Med. 2019;53(4):199–206.
  • Koomen BM, Badrising SK, van den Heuvel MM, et al. Comparability of PD-L1 immunohistochemistry assays for non-small cell lung cancer: a systematic review. Histopathology. 2019. doi: 10.1111/HIS.14040 2019 Dec 2 [Online ahead of print].
  • Erber R, Stohr R, Herlein S, et al. Comparison of PD-L1 mRNA expression measured with the checkpoint typer® assay with PD-L1 protein expression assessed with immunohistochemistry in non-small cell lung cancer. Anticancer Res. 2017;37(12):6771–6778.
  • Gafeer MM, Hosny Mohammed K, Ormenisan-Gherasim C, et al. Diagnostic utility of PD-L1 expression in lung adenocarcinoma: immunohistochemistry and RNA in situ hybridization. Appl Immunohistochem Mol Morphol. 2018;26(8):e86–e90.
  • Goodman AM, Piccioni D, Kato S, et al. Prevalence of PDL1 amplification and preliminary response to immune checkpoint blockade in solid tumors. JAMA Oncol. 2018;4(9):1237–1244.
  • Li C, Huang C, Mok TS, et al. Comparison of 22C3 PD-L1 expression between surgically resected specimens and paired tissue microarrays in non-small cell lung cancer. J Thorac Oncol. 2017;12(10):1536–1543.
  • Faulkner E, Annemans L, Garrison L, et al. Challenges in the development and reimbursement of personalized medicine-payer and manufacturer perspectives and implications for health economics and outcomes research: a report of the ISPOR personalized medicine special interest group. Value Health. 2012;15(8):1162–1171.
  • Garfield S, Polisena J, D SS, et al. Health technology assessment for molecular diagnostics: practices, challenges, and recommendations from the medical devices and diagnostics special interest group. Value Health. 2016;19(5):577–587.
  • Garinet S, Laurent-Puig P, Blons H, et al. Current and future molecular testing in NSCLC, what can we expect from new sequencing technologies? J Clin Med. 2018;7(6):144.