Treatment outcomes and prognostic factors in patients with driver mutant non-small cell lung cancer and de novo brain metastases.

De novo brain metastases Oncogene-driven advanced non-small cell lung cancer Survival related parameters

Journal

Scientific reports

ISSN: 2045-2322

Titre abrégé: Sci Rep

Pays: England

ID NLM: 101563288

Informations de publication

Date de publication:
09 Mar 2024

Historique:

received: 23 11 2023

accepted: 01 03 2024

medline: 10 3 2024

pubmed: 10 3 2024

entrez: 9 3 2024

Statut: epublish

Résumé

Central nervous system (CNS) metastases can be seen at a rate of 30% in advanced stages for patients with non-small cell lung cancer (NSCLC). Growing evidence indicates the predictive roles of driver gene mutations in the development of brain metastases (BM) in recent years, meaning that oncogene-driven NSCLC have a high incidence of BM at diagnosis. Today, 3rd generation targeted drugs with high intracranial efficacy, which can cross the blood-brain barrier, have made a positive contribution to survival for these patients with an increased propensity to BM. It is important to update the clinical and pathological factors reflected in the survival with real-life data. A multi-center, retrospective database of 306 patients diagnosed with driver mutant NSCLC and initially presented with BM between between November 2008 and September 2022 were analyzed. The median progression-free survival (mPFS) was 12.25 months (95% CI, 10-14.5). While 254 of the patients received tyrosine kinase inhibitor (TKI), 51 patients received chemotherapy as first line treatment. The median intracranial PFS (iPFS) was 18.5 months (95% CI, 14.8-22.2). The median overall survival (OS) was 29 months (95% CI, 25.2-33.0). It was found that having 3 or less BM and absence of extracranial metastases were significantly associated with better mOS and iPFS. The relationship between the size of BM and survival was found to be non-significant. Among patients with advanced NSCLC with de novo BM carrying a driver mutation, long-term progression-free and overall survival can be achieved with the advent of targeted agents with high CNS efficacy with more conservative and localized radiotherapy modalities.

Identifiants

DOI: 10.1038/s41598-024-56046-w PMID: 38461209

pubmed: 38461209

doi: 10.1038/s41598-024-56046-w

pii: 10.1038/s41598-024-56046-w

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

5820

Informations de copyright

Références

Komaki, R.U., & Ghia, A. J., Brain Metastasis from Lung Cancer, in Lung Cancer p. 572–589. (2014)

Yamanaka, R. Medical management of brain metastases from lung cancer (Review). Oncol. Rep. 22(6), 1269–1276 (2009).

doi: 10.3892/or_00000564 pubmed: 19885576

Germain, F. et al. Brain metastasis is an early manifestation of distant failure in stage III nonsmall cell lung cancer patients treated with radical chemoradiation therapy. Am. J. Clin. Oncol. 31(6), 561–566 (2008).

doi: 10.1097/COC.0b013e318172d5f9 pubmed: 19060588

Wang, H. et al. Driver genes as predictive indicators of brain metastasis in patients with advanced NSCLC: EGFR, ALK, and RET gene mutations. Cancer Med. 9(2), 487–495 (2020).

doi: 10.1002/cam4.2706 pubmed: 31769228

Tomasini, P. et al. EGFR and KRAS mutations predict the incidence and outcome of brain metastases in non-small cell lung cancer. Int. J. Mol. Sci. 17(12), 2132 (2016).

doi: 10.3390/ijms17122132 pubmed: 27999344 pmcid: 5187932

Iuchi, T. et al. Frequency of brain metastases in non-small-cell lung cancer, and their association with epidermal growth factor receptor mutations. Int. J. Clin. Oncol. 20(4), 674–679 (2015).

doi: 10.1007/s10147-014-0760-9 pubmed: 25336382

Patil, T. et al. The incidence of brain metastases in stage IV ROS1-rearranged non-small cell lung cancer and rate of central nervous system progression on crizotinib. J. Thorac. Oncol. 13(11), 1717–1726 (2018).

doi: 10.1016/j.jtho.2018.07.001 pubmed: 29981925 pmcid: 6204290

Wang, H. et al. Genes associated with increased brain metastasis risk in non-small cell lung cancer: Comprehensive genomic profiling of 61 resected brain metastases versus primary non-small cell lung cancer (Guangdong Association Study of Thoracic Oncology 1036). Cancer 125(20), 3535–3544 (2019).

doi: 10.1002/cncr.32372 pubmed: 31287555

Shih, D. J. H. et al. Genomic characterization of human brain metastases identifies drivers of metastatic lung adenocarcinoma. Nat. Genet. 52(4), 371–377 (2020).

doi: 10.1038/s41588-020-0592-7 pubmed: 32203465 pmcid: 7136154

Rangachari, D. et al. Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers. Lung Cancer 88(1), 108–111 (2015).

doi: 10.1016/j.lungcan.2015.01.020 pubmed: 25682925

Rakshit S, B.R., Desai A, et al., Brain metastases in non-small cell lungcancer in era of molecularly driven therapy., in European Lung Cancer Virtual Congress 2021.

Soria, J. C. et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N. Engl. J. Med. 378(2), 113–125 (2018).

doi: 10.1056/NEJMoa1713137 pubmed: 29151359

Reungwetwattana, T. et al. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer. J. Clin. Oncol. 2018, 2018783118 (2018).

Peters, S. et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N. Engl. J. Med. 377(9), 829–838 (2017).

doi: 10.1056/NEJMoa1704795 pubmed: 28586279

Camidge, D. R. et al. Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer. N. Engl. J. Med. 379(21), 2027–2039 (2018).

doi: 10.1056/NEJMoa1810171 pubmed: 30280657

Shaw, A. T. et al. First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer. N. Engl. J. Med. 383(21), 2018–2029 (2020).

doi: 10.1056/NEJMoa2027187 pubmed: 33207094

Kang, Y. et al. Advances in lung cancer driver genes associated with brain metastasis. Front Oncol 10, 606300 (2020).

doi: 10.3389/fonc.2020.606300 pubmed: 33537237

Arora, R.D., et al., Palliative Radiation Therapy for Brain Metastases, in StatPearls. 2022: Treasure Island.

Rosell, R. et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): A multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 13(3), 239–246 (2012).

doi: 10.1016/S1470-2045(11)70393-X pubmed: 22285168

Yang, J. C. et al. Symptom control and quality of life in LUX-Lung 3: A phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J. Clin. Oncol. 31(27), 3342–3350 (2013).

doi: 10.1200/JCO.2012.46.1764 pubmed: 23816967

Sperduto, P. W. et al. Estimating survival in patients with lung cancer and brain metastases: An update of the graded prognostic assessment for lung cancer using molecular markers (Lung-molGPA). JAMA Oncol. 3(6), 827–831 (2017).

doi: 10.1001/jamaoncol.2016.3834 pubmed: 27892978

Park, K. et al. Radiotherapy for brain metastasis and long-term survival. Sci. Rep. 11(1), 8046 (2021).

doi: 10.1038/s41598-021-87357-x pubmed: 33850188 pmcid: 8044241

El Shafie, R. A. et al. Effect of timing, technique and molecular features on brain control with local therapies in oncogene-driven lung cancer. ESMO Open 6(3), 100161 (2021).

doi: 10.1016/j.esmoop.2021.100161 pubmed: 34090172 pmcid: 8182387

De Carlo, E. et al. Brain metastases management in oncogene-addicted non-small cell lung cancer in the targeted therapies era. Int. J. Mol. Sci. 23(12), 6477 (2022).

doi: 10.3390/ijms23126477 pubmed: 35742920 pmcid: 9223862

Billena, C. et al. The role of targeted therapy and immune therapy in the management of non-small cell lung cancer brain metastases. Front. Oncol. 13, 1110440 (2023).

doi: 10.3389/fonc.2023.1110440 pubmed: 36910642 pmcid: 9997098

Ramalingam, S. S. et al. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N. Engl. J. Med. 382(1), 41–50 (2019).

doi: 10.1056/NEJMoa1913662 pubmed: 31751012

Nishino, M., Soejima, K. & Mitsudomi, T. Brain metastases in oncogene-driven non-small cell lung cancer. Transl. Lung Cancer Res. 8(Suppl 3), S298-s307 (2019).

doi: 10.21037/tlcr.2019.05.15 pubmed: 31857953 pmcid: 6894990

Gadgeel, S. et al. Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study. Ann. Oncol. 29(11), 2214–2222 (2018).

doi: 10.1093/annonc/mdy405 pubmed: 30215676 pmcid: 6290889

Shaw, A. T. et al. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: An international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 18(12), 1590–1599 (2017).

doi: 10.1016/S1470-2045(17)30680-0 pubmed: 29074098 pmcid: 5777233

Araki, T. et al. Current treatment strategies for EGFR-mutated non-small cell lung cancer: From first line to beyond osimertinib resistance. Jpn. J. Clin. Oncol. 53(7), 547–561 (2023).

doi: 10.1093/jjco/hyad052 pubmed: 37279591 pmcid: 10311169

Cho, B. C. et al. MARIPOSA: Phase 3 study of first-line amivantamab + lazertinib versus osimertinib in EGFR-mutant non-small-cell lung cancer. Fut. Oncol. 18(6), 639–647 (2022).

doi: 10.2217/fon-2021-0923

Jänne, P. A. et al. CNS efficacy of osimertinib with or without chemotherapy in epidermal growth factor receptor-mutated advanced non-small-cell lung cancer. J. Clin. Oncol. 2023, Jco2302219 (2023).

Passaro, A. et al. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: Primary results from the phase III MARIPOSA-2 study. Ann. Oncol. 35(1), 77–90 (2024).

doi: 10.1016/j.annonc.2023.10.117 pubmed: 37879444

Lee, J. et al. Combatting acquired resistance to osimertinib in EGFR-mutant lung cancer. Ther. Adv. Med. Oncol. 14, 17588359221144100 (2022).

doi: 10.1177/17588359221144099 pubmed: 36544540 pmcid: 9761802