{"id":46756,"date":"2024-08-27T08:00:00","date_gmt":"2024-08-27T08:00:00","guid":{"rendered":"http:\/\/3a6f13f7ad7aff5f8e9768bb669215a2"},"modified":"2024-11-03T15:11:48","modified_gmt":"2024-11-03T15:11:48","slug":"adding-upfront-srs-to-cns-penetrant-tki-improves-time-to-cns-progression-and-local-cns-control-but-not-os-in-patients-with-brain-metastases-from-egfr-and-alk-driven-nsclc","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/adding-upfront-srs-to-cns-penetrant-tki-improves-time-to-cns-progression-and-local-cns-control-but-not-os-in-patients-with-brain-metastases-from-egfr-and-alk-driven-nsclc\/","title":{"rendered":"Adding Upfront SRS to CNS-penetrant TKI Improves Time-to-CNS Progression and Local CNS Control, But Not OS, in Patients with Brain Metastases from EGFR- and ALK-driven NSCLC"},"content":{"rendered":"

The TURBO-NSCLC study is a multicentre analysis of outcomes for 317 tyrosine kinase inhibitor (TKI)-na\u00efve patients with EGFR<\/em>-mutated or ALK <\/em>fusion\u2013positive non-small cell lung cancer (NSCLC) with brain metastases who received either TKI alone or TKI plus upfront stereotactic radiosurgery (SRS). After adjustment for baseline differences between the treatment groups, TKI plus SRS was associated with a significant improvement in time to central nervous system (CNS) progression, with this effect being driven by superior local control with the use of upfront SRS. No significant differences between the treatment groups were observed in overall survival (OS) or other CNS-specific outcomes such as neurologic mortality or leptomeningeal progression.<\/p>\n

Patients with larger brain metastases were found to have an increased risk of CNS progression, and subgroup analyses suggested that patients with brain metastases \u22651 cm may benefit more from the addition of upfront SRS on endpoints including time to CNS progression and CNS progression-free survival (PFS) and event-free survival according to Dr. Chad G. Rusthoven of the Department of Radiation Oncology, University of Colorado in Aurora, CO, US and colleagues, who published the findings on 24 July 2024 in the JCO<\/em>.<\/p>\n

The authors wrote in the background that brain metastases are common in patients with NSCLC with EGFR <\/em>mutations and ALK<\/em> gene rearrangements. The radiation-based standard-of-care for limited brain metastases from NSCLC is SRS, which is better tolerated than whole-brain radiation and offers comparable survival for up to 15 brain metastases.<\/p>\n

Newer-generation TKIs targeting EGFR <\/em>and ALK<\/em> have demonstrated encouraging objective CNS response rates for brain metastases in the range of 55-90% in prospective data sets. There is a paucity of data comparing CNS-penetrant TKIs with and without upfront SRS, and cautionary results were observed in a large multi-institutional series reporting inferior OS with the omission of SRS in patients with EGFR<\/em>-mutated NSCLC treated with the first-generation TKI erlotinib.<\/p>\n

The investigators from 7 academic centres in the US conducted this multi-institutional retrospective cohort study to evaluate clinical outcomes in TKI-na\u00efve patients with untreated brain metastases from EGFR-<\/em> and ALK-<\/em>driven NSCLC who received newer-generation CNS-penetrant TKI alone versus TKI plus upfront SRS. They hypothesised that CNS control would be improved with the addition of SRS to CNS-penetrant TKIs. Time-to-CNS progression and OS were analyzed, with multivariable adjustment in Fine & Gray and Cox proportional hazards models for clinically relevant factors.<\/p>\n

From 2013 to 2022, 317 patients were identified of whom 200 treated with TKI only and 117 with TKI plus SRS. A total, 250 (79%) and 61 (19%) patients received osimertinib and alectinib. Patients receiving TKI plus SRS were more likely to have brain metastases \u22651 cm (p < 0.001) and neurologic symptoms (p < 0.001) at presentation. Median OS was similar between the TKI and TKI plus SRS groups with median 41 versus 40 months, respectively (p = 0.5).<\/p>\n

In a multivariable analysis, TKI plus SRS was associated with a significant improvement in time-to-CNS progression (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.42 to 0.96; p = 0.033). Local CNS control was significantly improved with TKI plus SRS (HR 0.30, 95% CI 0.16 to 0.55; p < 0.001), whereas no significant differences were observed in distant CNS control. Subgroup analyses demonstrated a greater benefit from TKI plus SRS in patients with brain metastases \u22651 cm in diameter for time-to-CNS progression and CNS PFS.<\/p>\n

The authors concluded that these data may better inform individualised treatment decisions for patients with brain metastases who are eligible for CNS-penetrant TKIs.<\/p>\n

This work was supported in party by grant from the US National Institutes of Health\/National Cancer Institute.<\/p>\n

The findings were presented in part at the ASCO 2024 Annual Meeting (2 June 2024; Chicago, IL, US).<\/p>\n

Reference<\/h3>\n

Pike LRG, Miao E, Boe LA, et al. <\/em>Tyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From EGFR and ALK Oncogene\u2013Driven Non\u2013Small Cell Lung Cancer (TURBO-NSCLC)<\/a>. JCO<\/em>; Published online 24 July 2024. DOI: https:\/\/doi.org\/10.1200\/JCO.23.02668<\/a><\/p>\n

Source<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

The TURBO-NSCLC study is a multicentre analysis of outcomes for 317 tyrosine kinase inhibitor (TKI)-na\u00efve patients with EGFR-mutated or ALK fusion\u2013positive non-small cell lung cancer (NSCLC) with brain metastases who received either TKI alone or TKI plus upfront stereotactic radiosurgery (SRS). After adjustment for baseline differences between the treatment groups, TKI plus SRS was associated […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[5137],"tags":[],"class_list":["post-46756","post","type-post","status-publish","format-standard","hentry","category-world-news"],"_links":{"self":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/46756","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/comments?post=46756"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/46756\/revisions"}],"predecessor-version":[{"id":46931,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/46756\/revisions\/46931"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=46756"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=46756"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=46756"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}