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Medical Oncology

, 36:4 | Cite as

Radiotherapy with the anti-programmed cell death ligand-1 immune checkpoint blocker avelumab: acute toxicities in triple-negative breast cancer

  • Eliana La Rocca
  • Michela Dispinzieri
  • Laura Lozza
  • Gabriella Mariani
  • Serena Di Cosimo
  • Massimiliano Gennaro
  • Riccardo Valdagni
  • Maria Carmen De SantisEmail author
Short Communication
  • 272 Downloads

Abstract

Triple-negative breast cancer (TNBC) is clinically the most aggressive breast cancer (BC) subtype. There is an urgent need for effective therapies for patients with TNBC. Recent findings confirm the important role of factors related to the immune system in the clinical outcome and response to treatment of TNBC patients. Avelumab selectively binds to PDL1, and competitively blocks its interaction with anti-programmed death 1 (anti-PD-1) antibodies. Unlike anti-PD-1 antibodies, which target T-cells, avelumab targets tumor cells, and is therefore expected to have fewer side effects, including a lower risk of Immune-Related Adverse Events (irAEs). Uncertainties remain regarding a potential synergy resulting in increased toxicities by combining radiotherapy and immune-checkpoint inhibitors (ICIs). Effects of concomitant ICIs with thoracic radiotherapy on pulmonary toxicities is not currently known. There are no published data available on the effects of combining anti-PD-L1 with adjuvant radiotherapy (RT) for BC in a clinical setting. We reported a preliminary experience on the first patient treated at the National Cancer Institute of Milan with the association of avelumab and concomitantly RT for TNBC.

Keywords

Breast cancer Concomitant radiotherapy Immunotherapy Safety Pulmonary toxicity 

Notes

Acknowledgements

The Authors would like to thank Prof. P. Conte and Prof. V. Guarneri, the PI and co-PI behind this study.

Compliance with ethical standards

Conflict of interest

we have no conflicts of interest to disclose.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The present study has been reviewed and approved by the Ethical Review Board of the National Cancer Institute, Italy.

Informed consent

Informed consent for publication of this case study was obtained from the patient concerned.

References

  1. 1.
    Bernier J, Poortmaans PM. Surgery and radiation therapy of triple negative breast cancers: From biology to clinics. Breast. 2016;28:148–55.  https://doi.org/10.1016/j.breast.2016.05.014.CrossRefPubMedGoogle Scholar
  2. 2.
    Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164–72.  https://doi.org/10.1016/S0140-6736(13)62422-8.CrossRefPubMedGoogle Scholar
  3. 3.
    Jézéquel P, Loussouarn D, Guérin-Charbonnel C, Campion L, Vanier A, Gouraud W, et al. Gene-expression molecular subtyping of triplenegative breast cancer tumours: importance of immune response. Breast Cancer Res. 2015;17:43.  https://doi.org/10.1186/s13058-015-0550-y.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Desmedt C, Di Leo A, de Azambuja E, Larsimont D, Haibe-Kains B, Selleslags J, et al. Multifactorial approach to predicting resistance to anthracyclines. J Clin Oncol. 2011;29(12):1578–86.  https://doi.org/10.1200/JCO.2010.31.2231.CrossRefPubMedGoogle Scholar
  5. 5.
    Adams S, Gray RJ, Demaria S, Goldstein L, Perez EA, Shulman LN, et al. Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol. 2011;29(12):1578–86.  https://doi.org/10.1200/JCO.2010.31.2231.CrossRefGoogle Scholar
  6. 6.
    Fausto Petrelli R, Ardito K, Borgonovo, et al. Haematological toxicities with immunotherapy in patients with cancer; a systematic review and metanalysis. Eur J Cancer 2018 103:7–16.  https://doi.org/10.1016/j.ejca.2018.07.129.
  7. 7.
    Louvel G, Bahleda R, Ammari S, et al. Immunotherapy and pulmonary toxicities: can concomitant immune-checkpoint inhibitors with radiotherapy increase the risk of radiation pneumonitis? Eur Respir J. 2018;51:1701737.  https://doi.org/10.1183/13993003.01737-2017.CrossRefPubMedGoogle Scholar
  8. 8.
    Kroeze SGC, Fritz C, Hoyer M, Lo SS, Ricardi U, Sahgal A, et al. Toxicity of concurrent stereotactic radiotherapy and targeted therapy or immunotherapy: A systematic review. Cancer Treat Rev. 2017;53:25–37.  https://doi.org/10.1016/j.ctrv.2016.11.013.CrossRefPubMedGoogle Scholar
  9. 9.
    Luke JJ, Lemons JM, Karrison TG, Pitroda SP, Melotek JM, Zha Y, et al. Safety and Clinical Activity of Pembrolizumab and Multisite Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors. J Clin Oncol. 2018.  https://doi.org/10.1200/JCO.2017.76.2229.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Shaverdian N, Lisberg AE, Bornazyan K, 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;18:895–903.CrossRefGoogle Scholar
  11. 11.
    Delaunay M, Cadranel J, Lusque A, et al. Immune-checkpoint inhibitors associated with interstitial lung disease in cancer patients. Eur Respir J. 2017;50:1700050.CrossRefGoogle Scholar
  12. 12.
    Montani D, Seferian A, Parent F, et al. Immune checkpoint inhibitor-associated interstitial lung diseases: some progress but still many issues. Eur Respir J. 2017;50:1701319.CrossRefGoogle Scholar
  13. 13.
    Omarini C, Thanopoulou E, Johnston SR. Pneumonitis and pulmonary fibrosis associated with breast cancer treatments. Breast Cancer Res Treat. 2014;146(2):245–58.  https://doi.org/10.1007/s10549-014-3016-5.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Eliana La Rocca
    • 1
    • 2
  • Michela Dispinzieri
    • 1
    • 2
  • Laura Lozza
    • 1
  • Gabriella Mariani
    • 3
  • Serena Di Cosimo
    • 4
  • Massimiliano Gennaro
    • 5
  • Riccardo Valdagni
    • 6
  • Maria Carmen De Santis
    • 1
    Email author
  1. 1.Radiotherapy Unit 1Fondazione IRCCS Istituto Nazionale dei TumoriMilanItaly
  2. 2.Department of Oncology and Hemato-oncologyUniversità degli Studi di MilanoMilanItaly
  3. 3.Department of OncologyFondazione IRCCS Istituto Nazionale dei TumoriMilanItaly
  4. 4.Department of Applied Research and Technological Development (DRAST)Fondazione IRCCS Istituto Nazionale dei TumoriMilanItaly
  5. 5.Breast Surgery UnitFondazione IRCCS Istituto Nazionale dei TumoriMilanItaly
  6. 6.Department of Oncology and Hemato-oncology, Radiation Oncology 1 and Prostate Cancer ProgramUniversità degli Studi di Milano, Fondazione IRCCS Istituto Nazionale dei TumoriMilanItaly

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