Immunotherapy in Non-Small Cell Lung Cancer Patients with Brain Metastases: Clinical Challenges and Future Directions

doi:10.3390/cancers13143407

Review

. 2021 Jul 7;13(14):3407.

doi: 10.3390/cancers13143407.

Immunotherapy in Non-Small Cell Lung Cancer Patients with Brain Metastases: Clinical Challenges and Future Directions

Ranjan Pathak¹, Arya Amini², Addie Hill¹, Erminia Massarelli¹, Ravi Salgia¹

Affiliations

¹ Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA 91010, USA.
² Department of Radiation Oncology, City of Hope, Duarte, CA 91010, USA.

PMID: 34298620
PMCID: PMC8303291
DOI: 10.3390/cancers13143407

Review

Immunotherapy in Non-Small Cell Lung Cancer Patients with Brain Metastases: Clinical Challenges and Future Directions

Ranjan Pathak et al. Cancers (Basel). 2021.

. 2021 Jul 7;13(14):3407.

doi: 10.3390/cancers13143407.

Authors

Ranjan Pathak¹, Arya Amini², Addie Hill¹, Erminia Massarelli¹, Ravi Salgia¹

Affiliations

¹ Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA 91010, USA.
² Department of Radiation Oncology, City of Hope, Duarte, CA 91010, USA.

PMID: 34298620
PMCID: PMC8303291
DOI: 10.3390/cancers13143407

Abstract

Immune checkpoint inhibitors have revolutionized the treatment landscape for patients with non-small cell lung cancers. Existing treatment paradigms for brain metastases in lung cancer patients leave patients with adverse neurocognitive function, poor quality of life, and dismal prognosis, thus highlighting the need to develop more effective systemic therapies. Although data are limited, emerging knowledge suggests promising activity and safety of immune checkpoint inhibitors in brain metastases in non-small cell lung cancer patients. This review aims to summarize the current data, highlight the challenges of incorporating immune checkpoint inhibitors in treating these patients, and identify areas for future research.

Keywords: PD-1; PD-L1; brain metastasis; immune checkpoint inhibitors; immunotherapy; non-small cell lung cancer.

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Conflict of interest statement

A.A. reports speaker bureau fees from Astra Zeneca and Takeda Pharmaceuticals. E.M. reports speaker bureau fees from Astra Zeneca and Merck, and advisory board fees from Merck and Genentech. R.S. reports speaker bureau participation with AstraZeneca and Merck and is an advisory board member for Janssen and Novartis. The remaining authors declare no conflict of interest.

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[1] Cagney D.N., Martin A.M., Catalano P.J., Redig A.J., Lin N.U., Lee E.Q., Wen P.Y., Dunn I.F., Bi W.L., Weiss S.E., et al. Incidence and Prognosis of Patients with Brain Metastases at Diagnosis of Systemic Malignancy: A Population-Based Study. Neuro-Oncology. 2017;19:1511–1521. doi: 10.1093/neuonc/nox077. - DOI - PMC - PubMed

[2] Cagney D.N., Martin A.M., Catalano P.J., Redig A.J., Lin N.U., Lee E.Q., Wen P.Y., Dunn I.F., Bi W.L., Weiss S.E., et al. Incidence and Prognosis of Patients with Brain Metastases at Diagnosis of Systemic Malignancy: A Population-Based Study. Neuro-Oncology. 2017;19:1511–1521. doi: 10.1093/neuonc/nox077. - DOI - PMC - PubMed

[3] Shin D.-Y., Na I.I., Kim C.H., Park S., Baek H., Yang S.H. EGFR Mutation and Brain Metastasis in Pulmonary Adenocarcinomas. J. Thorac. Oncol. Off. Publ. Int. Assoc. Study Lung Cancer. 2014;9:195–199. doi: 10.1097/JTO.0000000000000069. - DOI - PubMed

[4] Shin D.-Y., Na I.I., Kim C.H., Park S., Baek H., Yang S.H. EGFR Mutation and Brain Metastasis in Pulmonary Adenocarcinomas. J. Thorac. Oncol. Off. Publ. Int. Assoc. Study Lung Cancer. 2014;9:195–199. doi: 10.1097/JTO.0000000000000069. - DOI - PubMed

[5] Zhang I., Zaorsky N.G., Palmer J.D., Mehra R., Lu B. Targeting Brain Metastases in ALK-Rearranged Non-Small-Cell Lung Cancer. Lancet Oncol. 2015;16:e510–521. doi: 10.1016/S1470-2045(15)00013-3. - DOI - PubMed

[6] Zhang I., Zaorsky N.G., Palmer J.D., Mehra R., Lu B. Targeting Brain Metastases in ALK-Rearranged Non-Small-Cell Lung Cancer. Lancet Oncol. 2015;16:e510–521. doi: 10.1016/S1470-2045(15)00013-3. - DOI - PubMed

[7] Peters S., Bexelius C., Munk V., Leighl N. The Impact of Brain Metastasis on Quality of Life, Resource Utilization and Survival in Patients with Non-Small-Cell Lung Cancer. Cancer Treat. Rev. 2016;45:139–162. doi: 10.1016/j.ctrv.2016.03.009. - DOI - PubMed

[8] Peters S., Bexelius C., Munk V., Leighl N. The Impact of Brain Metastasis on Quality of Life, Resource Utilization and Survival in Patients with Non-Small-Cell Lung Cancer. Cancer Treat. Rev. 2016;45:139–162. doi: 10.1016/j.ctrv.2016.03.009. - DOI - PubMed

[9] El Rassy E., Botticella A., Kattan J., Le Péchoux C., Besse B., Hendriks L. Non-Small Cell Lung Cancer Brain Metastases and the Immune System: From Brain Metastases Development to Treatment. Cancer Treat. Rev. 2018;68:69–79. doi: 10.1016/j.ctrv.2018.05.015. - DOI - PubMed

[10] El Rassy E., Botticella A., Kattan J., Le Péchoux C., Besse B., Hendriks L. Non-Small Cell Lung Cancer Brain Metastases and the Immune System: From Brain Metastases Development to Treatment. Cancer Treat. Rev. 2018;68:69–79. doi: 10.1016/j.ctrv.2018.05.015. - DOI - PubMed

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Immunotherapy in Non-Small Cell Lung Cancer Patients with Brain Metastases: Clinical Challenges and Future Directions

Affiliations

Immunotherapy in Non-Small Cell Lung Cancer Patients with Brain Metastases: Clinical Challenges and Future Directions

Authors

Affiliations

Abstract

Conflict of interest statement

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