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Comparable outcomes of nivolumab in patients with advanced NSCLC presenting with or without brain metastases: a retrospective cohort study

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Abstract

Objective

This study aimed to determine whether there is a difference in the efficacy of nivolumab in patients with advanced non-small cell lung cancer (NSCLC) presenting with or without brain metastases.

Materials and methods

Patients with advanced NSCLC treated with nivolumab monotherapy were retrospectively analyzed. They were divided into two cohorts according to the presence or absence of brain metastases. The differences between the two cohorts in objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), duration of response (DOR) and overall survival (OS) were investigated, and the intracranial efficacy, including intracerebral objective response rate (IORR), intracranial disease control rate (IDCR) and intracranial progression-free survival (iPFS), were examined in the brain metastasis (BM) cohort.

Results

Seventy-three patients (32 with brain metastases and 41 without) were included. The ORRs of the BM cohort and the non-brain metastasis (non-BM) cohort were 25.0% and 19.5% (p = 0.574), DCRs were 53.1% and 56.1% (p = 0.800), respectively. Their median PFS were 2.8 and 4.9 months (p = 0.204), median DORs were 9.8 and 28.8 months (p = 0.003), and median OS were 14.8 and 20.2 months (p = 0.114), respectively. According to the Cox multivariate regression analysis, BM was not an independent prognostic factor. The IORR and IDCR of the BM cohort were 28.1% and 46.9%, respectively, with a median iPFS of 2.2 months.

Conclusions

The efficacy of nivolumab is comparable in patients with NSCLC presenting with and without brain metastases, but the results must be verified in large-scale prospective studies.

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Abbreviations

BMs:

Brain metastases

CFDA:

China Food and Drug Administration

CI:

Confidence interval

CNS:

Central nervous system

CR:

Complete remission

CT:

Computed tomography

DCR:

Disease control rate

DOR:

Duration of response

ECOG PS:

Eastern Cooperative Oncology Group Performance Status

FDA:

Food and Drug Administration

HR:

Hazard ratio

ICIs:

Immune checkpoint inhibitors

IDCR:

Intracranial disease control rate

IORR:

Intracerebral objective response rate

iPFS:

Intracranial progression-free survival

mAbs:

Monoclonal antibodies

non-BMs:

Non-brain metastases

NSCLC:

Non-small cell lung cancer

ORR:

Objective response rate

OS:

Overall survival

PD:

Progressive disease

PFS:

Progression-free survival

PR:

Partial remission

RT:

Radiotherapy

SD:

Stable disease

UICC:

Union for International Cancer Control

References

  1. Quint LE, Tummala S, Brisson LJ, Francis IR, Krupnick AS, Kazerooni EA, Iannettoni MD, Whyte RI, Orringer MB (1996) Distribution of distant metastases from newly diagnosed non-small cell lung cancer. Ann Thorac Surg 62(1):246–250

    Article  CAS  PubMed  Google Scholar 

  2. Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, Sneed PK, Chao ST, Weil RJ, Suh J, Bhatt A, Jensen AW, Brown PD, Shih HA, Kirkpatrick J, Gaspar LE, Fiveash JB, Chiang V, Knisely JP, Sperduto CM, Lin N, Mehta M (2012) Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol 30(4):419–425. https://doi.org/10.1200/JCO.2011.38.0527

    Article  PubMed  Google Scholar 

  3. Yang JJ, Zhou C, Huang Y, Feng J, Lu S, Song Y, Huang C, Wu G, Zhang L, Cheng Y, Hu C, Chen G, Zhang L, Liu X, Yan HH, Tan FL, Zhong W, Wu YL (2017) Icotinib versus whole-brain irradiation in patients with EGFR-mutant non-small-cell lung cancer and multiple brain metastases (BRAIN): a multicentre, phase 3, open-label, parallel, randomised controlled trial. Lancet Respir Med 5(9):707–716. https://doi.org/10.1016/S2213-2600(17)30262-X

    Article  CAS  PubMed  Google Scholar 

  4. 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 (2015) Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 373(17):1627–1639. https://doi.org/10.1056/NEJMoa1507643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. 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 (2015) Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 373(2):123–135. https://doi.org/10.1056/NEJMoa1504627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Herbst RS, Baas P, Kim DW, Felip E, Perez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB (2016) Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387(10027):1540–1550. https://doi.org/10.1016/S0140-6736(15)01281-7

    Article  CAS  PubMed  Google Scholar 

  7. 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 JS, Ballinger M, Kowanetz M, He P, Chen DS, Sandler A, Gandara DR, Group OAKS (2017) Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet 389(10066):255–265. https://doi.org/10.1016/S0140-6736(16)32517-X

    Article  PubMed  Google Scholar 

  8. Komaki R, Chang E (2004) Whole-brain radiation therapy. Intracranial metastases: current management strategies. Blackwell Publishing Malden, MA, pp 126–138

    Chapter  Google Scholar 

  9. Linskey ME, Andrews DW, Asher AL, Burri SH, Kondziolka D, Robinson PD, Ammirati M, Cobbs CS, Gaspar LE, Loeffler JS (2010) The role of stereotactic radiosurgery in the management of patients with newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol 96(1):45–68

    Article  PubMed  Google Scholar 

  10. Kalkanis SN, Kondziolka D, Gaspar LE, Burri SH, Asher AL, Cobbs CS, Ammirati M, Robinson PD, Andrews DW, Loeffler JS (2010) The role of surgical resection in the management of newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol 96(1):33–43

    Article  PubMed  Google Scholar 

  11. Fidler IJ, Yano S, Zhang R-d, Fujimaki T, Bucana CD (2002) The seed and soil hypothesis: vascularisation and brain metastases. Lancet Oncol 3(1):53–57

    Article  CAS  PubMed  Google Scholar 

  12. Lockman PR, Mittapalli RK, Taskar KS, Rudraraju V, Gril B, Bohn KA, Adkins CE, Roberts A, Thorsheim HR, Gaasch JA (2010) Heterogeneous blood-tumor barrier permeability determines drug efficacy in mouse brain metastases of breast cancer. Clin Cancer Res 1564:2010

    Google Scholar 

  13. Percy DB, Ribot EJ, Chen Y, McFadden C, Simedrea C, Steeg PS, Chambers AF, Foster PJ (2011) In vivo characterization of changing blood-tumor barrier permeability in a mouse model of breast cancer metastasis: a complementary magnetic resonance imaging approach. Invest Radiol 46(11):718–725

    Article  PubMed  PubMed Central  Google Scholar 

  14. Barlesi F, Gervais R, Lena H, Hureaux J, Berard H, Paillotin D, Bota S, Monnet I, Chajara A, Robinet G (2011) Pemetrexed and cisplatin as first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) with asymptomatic inoperable brain metastases: a multicenter phase II trial (GFPC 07-01). Ann Oncol 22(11):2466–2470

    Article  CAS  PubMed  Google Scholar 

  15. Bennouna J, Falchero L, Schott R, Bonnetain F, Coudert M, Yahia BBH, Chouaid C (2018) Bevacizumab in combination with platinum-based chemotherapy in patients with advanced non-squamous non-small cell lung cancer with or without brain metastases: a French cohort study (EOLE). Oncology 94(1):55–64

    Article  CAS  PubMed  Google Scholar 

  16. Goldberg SB, Gettinger SN, Mahajan A, Herbst RS, Chiang AC, Lilenbaum R, Jilaveanu L, Rowen E, Gerrish H, Komlo A (2018) Durability of brain metastasis response and overall survival in patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab. American Society of Clinical Oncology

  17. Gauvain C, Vauleon E, Chouaid C, Le Rhun E, Jabot L, Scherpereel A, Vinas F, Cortot AB, Monnet I (2018) Intracerebral efficacy and tolerance of nivolumab in non-small-cell lung cancer patients with brain metastases. Lung Cancer 116:62–66. https://doi.org/10.1016/j.lungcan.2017.12.008

    Article  PubMed  Google Scholar 

  18. Crinò L, Bronte G, Bidoli P, Cravero P, Minenza E, Cortesi E, Garassino MC, Proto C, Cappuzzo F, Grossi F (2019) Nivolumab and brain metastases in patients with advanced non-squamous non-small cell lung cancer. Lung Cancer

  19. Ferrara R, Lai WV, Hendriks L, Sabari JK, Caramella C, Plodkowski AJ, Halpenny D, Chaft JE, Planchard D, Riely GJ (2018) Impact of baseline steroids on efficacy of programmed cell death-1 and programmed death-ligand 1 blockade in patients with non–small-cell lung cancer. J Clin Oncol 36:2872–2878

    Article  PubMed  Google Scholar 

  20. Lu BY, Gupta R, Ribeiro M, Stewart T, Chiang V, Contessa JN, Adeniran A, Kluger HM, Jilaveanu L, Schalper KA (2018) PD-L1 expression and tumor-infiltrating lymphocytes in lung cancer brain metastases. American Society of Clinical Oncology

  21. Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M, Felip E, van den Heuvel MM, Ciuleanu T-E, Badin F (2017) First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. N Engl J Med 376(25):2415–2426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

American Journal Experts (AJE) provided English editing services. The authors thank all the patients and their families.

Funding

No relevant funding was received.

Author information

Author notes

  1. Guowei Zhang and Ruirui Cheng contributed equally to this study.

Authors and Affiliations

  1. Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, 450003, China

    Guowei Zhang, Huijuan Wang, Xiangtao Yan, Peng Li, Mina Zhang, Xiaojuan Zhang, Jinpo Yang, Yuanyuan Niu & Zhiyong Ma

  2. Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China

    Ruirui Cheng

  3. Department of Biotherapy, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, 450003, China

    Yong Zhang

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  1. Guowei Zhang
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Contributions

GZ and RC contributed to the study design, data analysis, interpretation of the findings, and preparation of the manuscript. ZM and HW contributed to the study design and critical review of the manuscript. YZ, XY and PL contributed to the data analysis, interpretation of the findings, and critical review of the manuscript. MZ, XZ, JY and YN contributed to the collection and organization of the data. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Zhiyong Ma.

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Conflict of interest

None of the authors have actual or potential conflicts of interest, including any financial, personal or other relationships with other people or organizations that could inappropriately influence (bias) this article, to declare.

Ethical approval

This study was approved by the ethics committees of the Affiliated Cancer Hospital and the First Affiliated Hospital of Zhengzhou University. The approval dates were October 12, 2018 and October 24, 2018, respectively. We confirm that all methods were performed in accordance with the relevant guidelines and regulations.

Informed consent

Due to the retrospective nature of the study and because no patient specimens were used, the requirement for informed consent was waived by the ethics committees.

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Zhang, G., Cheng, R., Wang, H. et al. Comparable outcomes of nivolumab in patients with advanced NSCLC presenting with or without brain metastases: a retrospective cohort study. Cancer Immunol Immunother 69, 399–405 (2020). https://doi.org/10.1007/s00262-019-02462-1

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  • DOI: https://doi.org/10.1007/s00262-019-02462-1

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