Characterization of central nervous system clinico-genomic outcomes in ALK-positive non-small cell lung cancer patients with brain metastases treated with alectinib Journal Article
| Authors: | Miao, E.; Eichholz, J. E.; Lebow, E. S.; Flynn, J.; Zhang, Z.; Walch, H.; Hubbeling, H.; Beal, K.; Moss, N. S.; Yu, K. K.; Meng, A.; Kelly, D. W.; Gomez, D. R.; Li, B. T.; Rimner, A.; Schultz, N.; Drilon, A.; Imber, B. S.; Pike, L. R. G. |
| Article Title: | Characterization of central nervous system clinico-genomic outcomes in ALK-positive non-small cell lung cancer patients with brain metastases treated with alectinib |
| Abstract: | Introduction: Highly effective brain-penetrant ALK-targeted tyrosine kinase inhibitors (TKIs) have been developed for the management of NSCLC patients with brain metastases (BM). Local therapy (LT) such as SRS or therapeutic craniotomy is increasingly being deferred for such patients. Herein we report detailed patient- and lesion-level intracranial outcomes and co-mutational genomic profiles from a cohort of NSCLC patients with BM treated with alectinib, with or without LT. Methods: We retrospectively reviewed ALK fusion-positive NSCLC patients with BMs who received alectinib at the diagnosis of BM from 1/2012 and 5/2021. Outcome variables included intracranial progression-free survival (iPFS), overall survival (OS), duration of TKI therapy, and CNS response rates. Genomic characteristics from tumor specimens were assessed with MSK-IMPACT, a next-generation sequencing (NGS)-based genomic profiling assay. Results: A total of 38 patients with 114 CNS lesions were included. Twelve of these patients also received contemporaneous LT (SRS, WBRT, or surgical resection). Maximal BM diameter in the TKI + LT group was greater (p < 0.003) but despite this difference, iPFS (TKI only, HR 1.21, 95 % CI 0.51–2.89; p = 0.66) and OS (TKI only, HR 5.99, 95 % CI 0.77–46.6; p = 0.052) were similar between groups and trended towards more favorable outcomes with the addition of LT. SMARCA4 co-alterations were associated with inferior OS (HR 8.76, 1.74–44.2; p = 0.009). Conclusions: Our study demonstrated that patients with ALK fusion-positive NSCLC treated with TKI + LT had larger BM and higher likelihood of pre-treatment neurologic symptoms. Despite these differences, iPFS was similar between groups. Results should be interpreted with caution as our study was limited by an underpowered sample size. SMARCA4 co-alterations were associated with inferior OS and these findings warrant further investigation. © 2023 Elsevier B.V. |
| Keywords: | adult; cancer survival; clinical article; controlled study; treatment outcome; aged; overall survival; clinical feature; cancer growth; treatment duration; follow up; progression free survival; cohort analysis; medical record review; retrospective study; central nervous system; clinical evaluation; gene fusion; brain metastasis; non-small cell lung cancer; alk; brain metastases; non small cell lung cancer; anaplastic lymphoma kinase; clinical outcome; genetic fingerprinting; brg1 protein; high throughput sequencing; alk gene; human; male; female; article; alectinib; chloroplast dna; cns radiation |
| Journal Title: | Lung Cancer |
| Volume: | 178 |
| ISSN: | 0169-5002 |
| Publisher: | Elsevier Ireland Ltd. |
| Date Published: | 2023-04-01 |
| Start Page: | 57 |
| End Page: | 65 |
| Language: | English |
| DOI: | 10.1016/j.lungcan.2023.02.005 |
| PUBMED: | 36780766 |
| PROVIDER: | scopus |
| PMCID: | PMC10065905 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author as Lukas Pike -- Export Date: 1 March 2023 -- Source: Scopus |
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