Skip to main content

Advertisement

SpringerLink
Log in

Tumor expression and usefulness as a biomarker of programmed death ligand 1 in advanced non-small cell lung cancer patients with preexisting interstitial lung disease

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

In non-small cell lung cancer (NSCLC) patients, the expression of tumor programmed death ligand 1 (PD-L1) is an important parameter for deciding the timing of the use of anti-programmed cell death 1 (PD-1) antibody. There has been increasing concern over the benefit of anti-PD-1 antibody in high-risk patients, such as those with preexisting interstitial lung disease (ILD). However, the status and value of PD-L1 as a predictive biomarker and the efficacy of anti-PD-1 antibody in NSCLC patients with preexisting ILD remains uncertain. We retrospectively reviewed the medical records of advanced/recurrent NSCLC patients who had undergone analysis of the tumor PD-L1 expression. We identified 358 patients with advanced/recurrent NSCLC who had undergone analysis of tumor PD-LI expression. Of these, 210 received anti-PD-1 antibody. Tumor-cell PD-L1 expression was similar between the groups with and without preexisting ILD (median, 35%; interquartile range, 0–70%; vs. median, 10%; interquartile range, 1–68%; p = 0.66). Of the 210 patients who received anti-PD-1 antibody, 14 patients had preexisting ILD. The progression-free survival (PFS) showed no significant difference between the patients receiving anti-PD-1 antibody with and without preexisting ILD (median PFS, 4.3 vs. 5.3 months; HR, 0.97; p = 0.84). Within the patients with preexisting ILD, the PFS was tended to be longer in the patients with tumor PD-L1 expression ≥ 50% than in those with tumor PD-L1 expression < 50% (median PFS, 12.5 vs. 2.5 months; HR, 0.47; p = 0.14). The value of PD-L1 expression as a biomarker may be comparable between patients with and without preexisting ILD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

PD-1:

Programmed cell death 1

PD-L1:

Programmed death ligand 1

NSCLC:

Non-small cell lung cancer

PFS:

Progression-free survival

OS:

Overall survival

ILD:

Interstitial lung disease

RECIST:

Response evaluation criteria in solid tumors

CT:

Computed tomography

HR:

Hazard ratio

CI:

Confidence interval

EGFR:

Epidermal growth factor receptor

ORR:

Overall response rate

DCR:

Disease control rate

References

  1. Horn L, Spigel DR, Vokes EE, Holgado E, Ready N, Steins M, Poddubskaya E, Borghaei H, Felip E, Paz-Ares L, Pluzanski A, Reckamp KL, Burgio MA, Kohlhaeufl M, Waterhouse D, Barlesi F, Antonia S, Arrieta O, Fayette J, Crino L, Rizvi N, Reck M, Hellmann MD, Geese WJ, Li A, Blackwood-Chirchir A, Healey D, Brahmer J, Eberhardt WEE. 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.

    Article  CAS  Google Scholar 

  2. Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Aren Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373(2):123–35.

    Article  CAS  Google Scholar 

  3. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhaufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crino L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627–39.

    Article  CAS  Google Scholar 

  4. Herbst RS, Baas P, Kim D-W, Felip E, Pérez-Gracia JL, Han J-Y, Molina J, Kim J-H, Arvis CD, Ahn M-J, Majem M, Fidler MJ, de Castro G, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. The Lancet. 2016;387(10027):1540–50.

    Article  CAS  Google Scholar 

  5. Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, Gadgeel SM, Hida T, Kowalski DM, Dols MC, Cortinovis DL, Leach J, Polikoff J, Barrios C, Kabbinavar F, Frontera OA, De Marinis F, Turna H, Lee J-S, Ballinger M, Kowanetz M, He P, Chen DS, Sandler A, Gandara DR. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. The Lancet. 2017;389(10066):255–65.

    Article  Google Scholar 

  6. Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O’Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR, Investigators K-. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823–33.

    Article  CAS  Google Scholar 

  7. King TE Jr. Clinical advances in the diagnosis and therapy of the interstitial lung diseases. Am J Respir Crit Care Med. 2005;172(3):268–79.

    Article  Google Scholar 

  8. Le Jeune I, Gribbin J, West J, Smith C, Cullinan P, Hubbard R. The incidence of cancer in patients with idiopathic pulmonary fibrosis and sarcoidosis in the UK. Respir Med. 2007;101(12):2534–40.

    Article  Google Scholar 

  9. Hubbard R, Venn A, Lewis S, Britton J. Lung cancer and cryptogenic fibrosing alveolitis. A population-based cohort study. Am J Respir Crit Care Med. 2000;61(1):5–8.

    Article  Google Scholar 

  10. Omori T, Tajiri M, Baba T, Ogura T, Iwasawa T, Okudela K, Takemura T, Oba MS, Maehara T, Nakayama H, Tsuboi M, Masuda M. Pulmonary resection for lung cancer in patients with idiopathic interstitial Pneumonia. Ann Thorac Surg. 2015;100(3):954–60.

    Article  Google Scholar 

  11. Fujimoto D, Kato R, Morimoto T, Shimizu R, Sato Y, Kogo M, Ito J, Teraoka S, Nagata K, Nakagawa A, Otsuka K, Tomii K. Characteristics and prognostic impact of pneumonitis during systemic anti-cancer therapy in patients with advanced non-small-cell lung cancer. PLoS ONE. 2016;11(12):e0168465.

    Article  Google Scholar 

  12. Fujimoto D, Sato Y, Morimoto T, Uehara K, Ito M, Otsuka K, Nagata K, Sakanoue I, Hamakawa H, Nakagawa A, Takahashi Y, Imai Y, Tomii K. Programmed cell death ligand 1 expression in non-small-cell lung cancer patients with interstitial lung disease: a matched case-control study. Clin Lung Cancer. 2018;19(5):e667–73.

    Article  CAS  Google Scholar 

  13. Igawa S, Sato Y, Ryuge S, Ichinoe M, Katono K, Hiyoshi Y, Otani S, Nagashio R, Nakashima H, Katagiri M, Sasaki J, Murakumo Y, Satoh Y, Masuda N. Impact of PD-L1 expression in patients with surgically resected non-small-cell lung cancer. Oncology. 2017;92(5):283–90.

    Article  CAS  Google Scholar 

  14. Shimoji M, Shimizu S, Sato K, Suda K, Kobayashi Y, Tomizawa K, Takemoto T, Mitsudomi T. Clinical and pathologic features of lung cancer expressing programmed cell death ligand 1 (PD-L1). Lung Cancer. 2016;98:69–75.

    Article  Google Scholar 

  15. Fujimoto D, Tomii K, Otoshi T, Kawamura T, Tamai K, Takeshita J, Tanaka K, Matsumoto T, Monden K, Nagata K, Otsuka K, Nakagawa A, Hata A, Tachikawa R, Otsuka K, Hamakawa H, Katakami N, Takahashi Y, Imai Y. Preexisting interstitial lung disease is inversely correlated to tumor epidermal growth factor receptor mutation in patients with lung adenocarcinoma. Lung Cancer. 2013;80(2):159–64.

    Article  Google Scholar 

  16. Mizushima Y, Kobayashi M. Clinical characteristics of synchronous multiple lung cancer associated with idiopathic pulmonary fibrosis. A review of Japanese cases. Chest. 1995;108(5):1272–7.

    Article  CAS  Google Scholar 

  17. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn MJ, Felip E, Lee JS, Hellmann MD, Hamid O, Goldman JW, Soria JC, Dolled-Filhart M, Rutledge RZ, Zhang J, Lunceford JK, Rangwala R, Lubiniecki GM, Roach C, Emancipator K, Gandhi L, Investigators K-. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–28.

    Article  Google Scholar 

  18. Kenmotsu H, Naito T, Kimura M, Ono A, Shukuya T, Nakamura Y, Tsuya A, Kaira K, Murakami H, Takahashi T, Endo M, Yamamoto N. The risk of cytotoxic chemotherapy-related exacerbation of interstitial lung disease with lung cancer. J Thorac Oncol. 2011;6(7):1242–6.

    Article  Google Scholar 

  19. Ando M, Okamoto I, Yamamoto N, Takeda K, Tamura K, Seto T, Ariyoshi Y, Fukuoka M. Predictive factors for interstitial lung disease, antitumor response, and survival in non-small-cell lung cancer patients treated with gefitinib. J Clin Oncol. 2006;24(16):2549–56.

    Article  CAS  Google Scholar 

  20. Naidoo J, Wang X, Woo KM, Iyriboz T, Halpenny D, Cunningham J, Chaft JE, Segal NH, Callahan MK, Lesokhin AM, Rosenberg J, Voss M, Rudin CM, Rizvi H, Hou X, Rodriguez K, Albano M, Gordon RA, Leduc C, Rekhtman N, Harris B, Menzies AM, Guminski AD, Carlino MS, Kong BY, Wolchok JD, Postow MA, Long GV, Hellmann MD. Pneumonitis in patients treated with anti-programmed death 1/programmed death ligand 1 therapy. J Clin Oncol. 2016;35(7):709.

    Article  Google Scholar 

  21. Nishino M, Ramaiya NH, Awad MM, Sholl LM, Maattala JA, Taibi M, Hatabu H, Ott PA, Armand PF, Hodi FS. PD-1 inhibitor-related pneumonitis in advanced cancer patients: radiographic patterns and clinical course. Clin Cancer Res. 2016;22(24):6051–60.

    Article  CAS  Google Scholar 

  22. Weber JS, Hodi FS, Wolchok JD, Topalian SL, Schadendorf D, Larkin J, Sznol M, Long GV, Li H, Waxman IM, Jiang J, Robert C. Safety profile of nivolumab monotherapy: a pooled analysis of patients with advanced melanoma. J Clin Oncol. 2017;35(7):785–92.

    Article  CAS  Google Scholar 

  23. Michot JM, Bigenwald C, Champiat S, Collins M, Carbonnel F, Postel-Vinay S, Berdelou A, Varga A, Bahleda R, Hollebecque A, Massard C, Fuerea A, Ribrag V, Gazzah A, Armand JP, Amellal N, Angevin E, Noel N, Boutros C, Mateus C, Robert C, Soria JC, Marabelle A, Lambotte O. Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer. 2016;54:139–48.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan

    Ryota Shibaki, Shuji Murakami, Yuji Matsumoto, Yasushi Goto, Shintaro Kanda, Hidehito Horinouchi, Yutaka Fujiwara, Noboru Yamamoto & Yuichiro Ohe

  2. Department of Pulmonary Medicine and Oncology, Wakayama Medical University, Wakayama, Japan

    Ryota Shibaki & Nobuyuki Yamamoto

  3. Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan

    Noriko Motoi

  4. Department of Diagnostic Radiology, National Cancer Center Hospital, Tokyo, Japan

    Masahiko Kusumoto

Authors
  1. Ryota Shibaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shuji Murakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuji Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yasushi Goto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shintaro Kanda
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hidehito Horinouchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yutaka Fujiwara
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nobuyuki Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Noriko Motoi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Masahiko Kusumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Noboru Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yuichiro Ohe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shuji Murakami.

Ethics declarations

Conflict of interest

SM has served on speakers’ bureaus for Taiho Pharmaceutical and Ono Pharmaceutical. YG has had consulting/advisory roles for Taiho Pharmaceutical; has served on speakers’ bureaus for Taiho Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, MSD; and has received research funding from Taiho Pharmaceutical, Bristol-Myers Squibb, and Ono Pharmaceutical. SK has received research funding from Ono Pharmaceutical and has received honoraria from Ono Pharmaceutical, and Bristol-Myers Squibb. HH has received research funding from MSD, Bristol-Myers Squibb, Ono Pharmaceutical, and Taiho Pharmaceutical. YF has received research funding from MSD and has served on speakers’ bureaus from MSD, Taiho Pharmaceutical, Bristol-Myers Squibb, and Ono Pharmaceutical. NY has had consulting/advisory roles for Taiho Pharmaceutical; has served on speakers’ bureaus for Ono Pharmaceutical, Bristol-Myers Squibb, MSD; and has received honoraria from Ono Pharmaceutical, and MSD. NY has received research funding from Taiho Pharmaceutical, Bristol-Myers Squibb, and Ono Pharmaceutical and has served on speakers’ bureaus from Bristol-Myers Squibb, and Ono Pharmaceutical. YO has received research funding and honoraria from Taiho Pharmaceutical, MSD. All remaining authors have declared no conflict of interest.

Ethical approval

This study was approved by National Cancer Center Hospital Japan and has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. This study involved retrospective analysis of existing data with no patient intervention or interaction.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shibaki, R., Murakami, S., Matsumoto, Y. et al. Tumor expression and usefulness as a biomarker of programmed death ligand 1 in advanced non-small cell lung cancer patients with preexisting interstitial lung disease. Med Oncol 36, 49 (2019). https://doi.org/10.1007/s12032-019-1274-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-019-1274-0

Keywords

Search

Navigation