Top

Clinical and Translational Oncology

Published in:

11-08-2023 | Bone Metastasis | RESEARCH ARTICLE

Impact of bone metastasis on the prognosis of non-small cell lung cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis

Authors: Lina Liu, Zhongyi Shi, Xingdong Qiu

Published in: Clinical and Translational Oncology | Issue 3/2024

Abstract

Background

This review was implemented to examine the impact of bone metastasis on the prognosis of non-small cell lung cancer patients (NSCLC) treated with immune checkpoint inhibitors (ICIs).

Methods

A literature search was conducted in the PubMed, CENTRAL, Web of Science, and Embase databases up to 4th September 2022. Multivariable adjusted data were pooled in a random-effects model.

Results

13 studies were included. On a combined analysis of 10 studies, it was noted that bony metastasis was associated with poor overall survival (OS) in NSCLC patients treated with ICIs (HR: 1.55 95% CI 1.24, 1.94 I² = 69% p = 0.001). Meta-analysis of seven studies showed that bony metastasis was not associated with poor progression-free survival (PFS) in NSCLC patients treated with ICIs (HR: 1.31 95% CI 0.85, 2.01 I² = 85% p = 0.22). Meta-regression analysis using the moderator's age, male gender, smoking history, squamous histology, and ICI as 1st line therapy for the outcome OS was not statistically significant.

Conclusion

The presence of bone metastasis is a predictor of poor OS in NSCLC treated with ICIs. However, PFS does not seem to be influenced by the presence of bone metastasis. Clinicians should prioritize the management of NSCLC patients with bone metastasis and explore the use of combination therapies to achieve optimal results. Further studies taking into account different combination therapies for such patients would strengthen the evidence.

Available only for authorised users

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.CrossRefPubMed

Schabath MB, Cote ML. Cancer Progress and Priorities: Lung Cancer. Cancer Epidemiol Biomarkers Prev. 2019;28:1563.CrossRefPubMedPubMedCentral

Duma N, Santana-Davila R, Molina JR. Non-Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment. Mayo Clin Proc. 2019;94:1623–40.CrossRefPubMed

Van Meerbeeck JP, Fennell DA, De Ruysscher DKM. Small-cell lung cancer. Lancet (London, England). 2011;378:1741–55.CrossRefPubMed

Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin. 2019;69:363–85. https://doi.org/10.3322/caac.21565.CrossRefPubMed

Howlader N, Forjaz G, Mooradian MJ, Meza R, Kong CY, Cronin KA, et al. The Effect of Advances in Lung-Cancer Treatment on Population Mortality. N Engl J Med. 2020;383:640–9.CrossRefPubMedPubMedCentral

Huang Y, Zhu L, Guo T, Chen W, Zhang Z, Li W, et al. Metastatic sites as predictors in advanced NSCLC treated with PD-1 inhibitors: a systematic review and meta-analysis. Hum Vaccin Immunother. 2021;17:1278–87.CrossRefPubMed

Kitadai R, Okuma Y, Hakozaki T, Hosomi Y. The efficacy of immune checkpoint inhibitors in advanced non-small-cell lung cancer with liver metastases. J Cancer Res Clin Oncol. 2020;146:777–85.CrossRefPubMed

Zhang G, Cheng R, Wang H, Zhang Y, Yan X, Li P, et al. Comparable outcomes of nivolumab in patients with advanced NSCLC presenting with or without brain metastases: a retrospective cohort study. Cancer Immunol Immunother. 2020;69:399–405.CrossRefPubMed

10.

Kuchuk M, Addison CL, Clemons M, Kuchuk I, Wheatley-Price P. Incidence and consequences of bone metastases in lung cancer patients. J bone Oncol. 2013;2:22–9.CrossRefPubMedPubMedCentral

11.

Sugiura H, Yamada K, Sugiura T, Hida T, Mitsudomi T. Predictors of survival in patients with bone metastasis of lung cancer. Clin Orthop Relat Res. 2008;466:729–36.CrossRefPubMedPubMedCentral

12.

Scagliotti GV, Hirsh V, Siena S, Henry DH, Woll PJ, Manegold C, et al. Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomized phase 3 study. J Thorac Oncol. 2012;7:1823–9.CrossRefPubMed

13.

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. Int J Surg. 2021;88: 105906.CrossRefPubMed

14.

Wells G, Shea B, O’Connell D, Peterson J, Welch V, Losos M et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp (accessed 30 Oct2020).

15.

Juan ZY, Song CX, Zhou R, Dong CY, Chuan MH, Zhen XZ, et al. Bone metastasis attenuates efficacy of immune checkpoint inhibitors and displays ‘cold’ immune characteristics in Non-small cell lung cancer. Lung Cancer. 2022;166:189–96.CrossRef

16.

Wu Y, Wu H, Lin M, Liu T, Li J. Factors associated with immunotherapy respond and survival in advanced non-small cell lung cancer patients. Transl Oncol. 2022. https://doi.org/10.1016/J.TRANON.2021.101268.CrossRefPubMedPubMedCentral

17.

Qin A, Zhao S, Miah A, Wei L, Patel S, Johns A, et al. Bone Metastases, Skeletal-Related Events, and Survival in Patients With Metastatic Non-Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitors. J Natl Compr Canc Netw. 2021;19:915–21.CrossRefPubMedPubMedCentral

18.

Galland L, Lecuelle J, Favier L, Fraisse C, Lagrange A, Kaderbhai C, et al. Splenic volume as a surrogate marker of immune checkpoint inhibitor efficacy in metastatic non small cell lung cancer. Cancers (Basel). 2021. https://doi.org/10.3390/CANCERS13123020.CrossRefPubMed

19.

Gu X, Shi Z, Shao L, Zhang Y, Zhang Y, Song Z, et al. Efficacy and safety of maintenance immune checkpoint inhibitors with or without pemetrexed in advanced non-squamous non-small cell lung cancer: a retrospective study. BMC Cancer. 2022. https://doi.org/10.1186/S12885-022-09674-2.CrossRefPubMedPubMedCentral

20.

Ruiz-Patiño A, Arrieta O, Cardona AF, Martín C, Raez LE, Zatarain-Barrón ZL, et al. Immunotherapy at any line of treatment improves survival in patients with advanced metastatic non-small cell lung cancer (NSCLC) compared with chemotherapy (Quijote-CLICaP). Thorac cancer. 2020;11:353–61.CrossRefPubMed

21.

Li X, Wang L, Chen S, Zhou F, Zhao J, Zhao W, et al. Adverse impact of bone metastases on clinical outcomes of patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors. Thorac cancer. 2020;11:2812–9.CrossRefPubMedPubMedCentral

22.

Kawachi H, Tamiya M, Tamiya A, Ishii S, Hirano K, Matsumoto H, et al. Association between metastatic sites and first-line pembrolizumab treatment outcome for advanced non-small cell lung cancer with high PD-L1 expression: a retrospective multicenter cohort study. Invest New Drugs. 2020;38:211–8.CrossRefPubMed

23.

Dallolio FG, Gelsomino F, Conci N, Marcolin L, De Giglio A, Grilli G, et al. PD-L1 Expression in Circulating Tumor Cells as a Promising Prognostic Biomarker in Advanced Non-small-cell Lung Cancer Treated with Immune Checkpoint Inhibitors. Clin Lung Cancer. 2021;22:423–31.CrossRefPubMed

24.

Prelaj A, Ferrara R, Rebuzzi SE, Proto C, Signorelli D, Galli G, et al. EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort. Cancers (Basel). 2019. https://doi.org/10.3390/CANCERS11121954.CrossRefPubMed

25.

Landi L, Dincà F, Gelibter A, Chiari R, Grossi F, Delmonte A, et al. Bone metastases and immunotherapy in patients with advanced non-small-cell lung cancer. J Immunother Cancer. 2019. https://doi.org/10.1186/S40425-019-0793-8.CrossRefPubMedPubMedCentral

26.

Garde-Noguera J, Martin-Martorell P, De Julián M, Perez-Altozano J, Salvador-Coloma C, García-Sanchez J, et al. Predictive and prognostic clinical and pathological factors of nivolumab efficacy in non-small-cell lung cancer patients. Clin Transl Oncol. 2018;20:1072–9.CrossRefPubMed

27.

Fukui T, Okuma Y, Nakahara Y, Otani S, Igawa S, Katagiri M, et al. Activity of Nivolumab and Utility of Neutrophil-to-Lymphocyte Ratio as a Predictive Biomarker for Advanced Non-Small-Cell Lung Cancer: A Prospective Observational Study. Clin Lung Cancer. 2019;20:208-214.e2.CrossRefPubMed

28.

Zheng XQ, Huang JF, Lin JL, Chen L, Zhou TT, Chen D, et al. Incidence, prognostic factors, and a nomogram of lung cancer with bone metastasis at initial diagnosis: a population-based study. Transl lung cancer Res. 2019;8:367–79.CrossRefPubMedPubMedCentral

29.

Knapp BJ, Devarakonda S, Govindan R. Bone metastases in non-small cell lung cancer: a narrative review. J Thorac Dis. 2022;14:1696–712.CrossRefPubMedPubMedCentral

30.

Lecouvet FE, Talbot JN, Messiou C, Bourguet P, Liu Y, De Souza NM. Monitoring the response of bone metastases to treatment with Magnetic Resonance Imaging and nuclear medicine techniques: a review and position statement by the European Organisation for Research and Treatment of Cancer imaging group. Eur J Cancer. 2014;50:2519–31.CrossRefPubMed

31.

Xiang L, Gilkes DM. The Contribution of the Immune System in Bone Metastasis Pathogenesis. Int J Mol Sci. 2019. https://doi.org/10.3390/IJMS20040999.CrossRefPubMedPubMedCentral

32.

Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gümüş M, Mazières J, et al. Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018;379:2040–51.CrossRefPubMed

33.

Gandhi L, Rodríguez-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;378:2078–92.CrossRefPubMed

Title: Impact of bone metastasis on the prognosis of non-small cell lung cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis
Authors: Lina Liu
Zhongyi Shi
Xingdong Qiu
Publication date: 11-08-2023
Publisher: Springer International Publishing
Keywords: Bone Metastasis
NSCLC
NSCLC
Metastasis
Lung Cancer
Lung Cancer
Lung Cancer
Checkpoint Inhibitors
Published in: Clinical and Translational Oncology / Issue 3/2024
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI: https://doi.org/10.1007/s12094-023-03300-8

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2024

Difficulties on the access to innovative targeted therapies for lung cancer in Spain

LncRNA XXYLT1-AS2 promotes tumor progression via autophagy inhibition through ubiquitinated degradation of TFEB in hepatocellular carcinoma

Case–control study assessing the impact of COVID19 in advanced kidney cancer patients treated with antiangiogenics or immunotherapy: the COVID-REN study

Influence of cancer-directed surgery on the prognosis of liver metastases from gastric cancer

Clinical significance of CD166 and HER-2 in different types of gastric cancer

CircRNA-regulated glucose metabolism in ovarian cancer: an emerging landscape for therapeutic intervention

Keynote webinar | Spotlight on antibody–drug conjugates in cancer