Complete remission in an elderly patient with non-small cell lung cancer and brain metastasis using immunotherapy plus chemotherapy: a clinical case

Lung cancer remains a leading cause of cancer-related mortality, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Among its subtypes, adenocarcinoma is most prevalent. Stage IV NSCLC comes with a poor prognosis, particularly in elderly patients with comorbidities. Programmed death-ligand 1 (PD-L1) checkpoint inhibitors have demonstrated promising efficacy, including in cases with brain metastases.
Case report. The case concerns an 83-year-old woman with diabetes mellitus, arterial hypertension, and atrial fibrillation, diagnosed with stage IVB poorly differentiated lung adenocarcinoma which was confirmed by a percutaneous lung biopsy. PD-L1 expression was 40%. Magnetic resonance imaging identified a solitary brain metastasis. The patient was treated with dexamethasone and a CheckMate 9LA protocol was initiated with reduced-dose carboplatin, pemetrexed, nivolumab, and ipilimumab. A two years follow-up positron emission tomography showed a significant reduction in lung cancer. The brain lesions had almost disappeared, and in addition a clinical improvement could be observed.
Discussion. This case underscores the potential for durable remission and improved quality of life through individualized treatment strategies in older patients with advanced NSCLC and brain involvement

1. Rodríguez-Cid J.R., Chards S.C., González-Espinoza I.R., et al. A comparative study of immunotherapy as second-line treatment and beyond in patients with advanced non-small-cell lung carcinoma. Lung Cancer Manag. 2021 Mar 11; 10(3); LMT47. https://doi.org/10.2217/lmt-2020-0027. PMID: 34408789

2. Leone G.M., Candido S., Lavoro A., et al. Clinical relevance of targeted therapy and immune-checkpoint inhibition in lung cancer. Pharmaceutics. 2023 Apr; 15(4): 1252. https://doi.org/10.3390/pharmaceutics15041252. Epub 2023 Apr 16. PMID: 37111737

3. Chen P., Liu Y., Wen Y., et al. Non-small cell lung cancer in China. Cancer Commun (Lond). 2022 Oct; 42(10): 937-970. https://doi.org/10.1002/cac2.12359. Epub 2022 Sep 8. PMID: 36075878

4. Nicholson A.G., Tsao M.S., Beasley M.B., et al. The 2021 WHO classification of lung tumors: impact of advances since 2015. J Thorac Oncol. 2022 Mar; 17(3): 362–387. https://doi.org/10.1016/j.jtho.2021.11.003. Epub 2021 Nov 20. PMID: 34808341

5. Jiang K., Parker M., Materi J., et al. Epidemiology and survival outcomes of synchronous and metachronous brain metastases: a retrospective population-based study. Neurosurg Focus. 2023 Aug; 55(2): E3. https://doi.org/10.3171/2023.5.FOCUS23212. PMID: 37527669

6. Wang Q., Li J., Liang X., Zhan Q. Improved survival with surgical treatment of primary lung lesions in non-small cell lung cancer with brain metastases: a propensity-matched analysis of Surveillance, Epidemiology, and End Results database. Front Oncol. 2022 Jul; 12: 888999. https://doi.org/10.3389/fonc.2022.888999. PMID: 35936705

7. Schmidt M., Nitz U., Reimer T., et al. Adjuvant capecitabine versus nihil in older patients with node-positive/high-risk nodenegative early breast cancer receiving ibandronate – The ICE randomized clinical trial. Eur J Cancer. 2023 Nov; 194: 113324. https://doi.org/10.1016/j.ejca.2023.113324. Epub 2023 Sep 7. PMID: 37797387

8. Huang Q., Liu L., Xiao D., et al. CD44+ lung cancer stem cell-derived pericyte-like cells cause brain metastases through GPR124- enhanced trans-endothelial migration. Cancer Cell. 2023 Sep; 41(9): 1621–1636.e8. https://doi.org/10.1016/j.ccell.2023.07.012. Epub 2023 Aug 17. PMID: 37595587

9. Nishino M., Soejima K., Mitsudomi T., et al. Brain metastases in oncogene-driven non-small cell lung cancer. Transl Lung Cancer Res. 2019 Nov; 8(Suppl 3): S298–S307. https://doi.org/10.21037/tlcr.2019.05.15. PMID: 31857953

10. Sun C., Zhou F., Li X., et al. PD-1/PD-L1 inhibitor combined with chemotherapy can improve the survival of non-small cell lung cancer patients with brain metastases. Onco Targets Ther. 2020 Dec; 13: 12777–12786. https://doi.org/10.2147/OTT.S286600. PMID: 33363383

11. Reck M., Ciuleanu T.E., Cobo M., et al. First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in advanced non-small-cell lung cancer: CheckMate 9LA 2-year update. ESMO Open. 2021 Oct; 6(5): 100273. https://doi.org/10.1016/j.esmoop.2021.100273. Epub 2021 Oct 1. Erratum in: ESMO Open. 2021 Dec; 6(6): 100345. https://doi.org/10.1016/j.esmoop.2021.100345. PMID: 34607285

12. Tai Q., Zhang L., Hu X., et al. Clinical characteristics and treatments of large cell lung carcinoma: a retrospective study using SEER data. Transl Cancer Res. 2020 Mar; 9(3): 1455–1464. https://doi.org/10.21037/tcr.2020.01.40. PMID: 35117493

13. Zhang S. Diagnostic Imaging of Lung Cancers. Springer. 2024: 103–109. https://doi.org/10.1007/978-981-99-6815-2. ISBN978- 981-99-6814-5

14. Martin-Deleon R., Teixido C., Lucena C.M., et al. EBUS-TBNA cytological samples for comprehensive molecular testing in nonsmall cell lung cancer. Cancers (Basel). 2021 Apr; 13(9): 2084. https://doi.org/10.3390/cancers13092084. PMID: 33923116

15. Rodak O., Peris-Díaz M.D., Olbromski M., et al. Current landscape of non-small cell lung cancer: epidemiology, histological classification, targeted therapies, and immunotherapy. Cancers (Basel). 2021 Sep; 13(18): 4705. https://doi.org/10.3390/cancers13184705. PMID: 34572931

16. John T., Sakai H., Ikeda S., et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in advanced non-small cell lung cancer: a subanalysis of Asian patients in CheckMate 9LA. Int J Clin Oncol. 2022 Apr; 27(4): 695–706. https://doi.org/10.1007/s10147-022-02120-0. Epub 2022 Feb 19. PMID: 35182247

17. Socha J., Rychter A., Kepka L., et al. Management of brain metastases in elderly patients with lung cancer. J Thorac Dis. 2021 May; 13(5): 3295–3307. https://doi.org/10.21037/jtd-2019-rbmlc-05. PMID: 34164222

18. Shalata W., Yakobson A., Dudnik Y., et al. Multi-center real-world outcomes of nivolumab plus ipilimumab and chemotherapy in patients with metastatic non-small-cell lung cancer. Biomedicines. 2023 Aug; 11(9): 2438. https://doi.org/10.3390/biomedicines11092438. PMID: 37760878

19. Saxena P., Singh P.K., Malik P.S., Singh N. Immunotherapy alone or in combination with chemotherapy as first-line treatment of non-small cell lung cancer. Cancer Treat Oncol. 2020 Jul 27;21(8):69. https://doi.org/10.1007/s11864-020-00768-2. Erratum in: Curr Treat Options Oncol. 2020 Sep 12;21(11):91. https://doi.org/10.1007/s11864-020-00789-x. PMID: 32720019

20. Shiravand Y., Khodadadi F., Kashani S.M.A., et al. Immune checkpoint inhibitors in cancer therapy. Curr Oncol. 2022 Apr; 29(5): 3044–3060. https://doi.org/10.3390/curroncol29050247. PMID: 35621637

21. Tawbi H.A., Forsyth P.A., Algazi A., et al. Combined nivolumab and ipilimumab in melanoma metastatic to the brain. N Engl J Med. 2018 Aug; 379(8): 722–730. https://doi.org/10.1056/NEJMoa1805453. PMID: 30134131