Overall survival benefit of osimertinib and clinical value of upfront cranial local therapy in untreated EGFR‐mutant nonsmall cell lung cancer with brain metastasis. Issue 8 (6th January 2022)

• Record Type: Journal Article
• Authors: Zhao, Yang; Li, Shuyan; Yang, Xi; Chu, Li; Wang, Shengping; Tong, Tong; Chu, Xiao; Yu, Fan; Zeng, Ya; Guo, Tiantian; Zhou, Yue; Zou, Liqing; Li, Yida; Ni, Jianjiao; Zhu, Zhengfei
• Is Part Of: International journal of cancer. Volume 150:Issue 8(2022)
• Page Start: 1318
• Page End: 1328
• Publication Date: 2022-01-06
• Subjects: brain metastasis -- cranial local therapy -- EGFR -- nonsmall cell lung cancer -- osimertinib; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.33904
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract: Osimertinib, as a third‐generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), showed more potent efficacy against brain metastasis (BM) in untreated EGFR‐mutant nonsmall cell lung cancer (NSCLC) in the FLAURA study. However, the overall survival (OS) benefit of osimertinib and clinical value of cranial local therapy (CLT) in these patients remain undetermined. Here we conducted a retrospective study involving untreated EGFR‐mutant NSCLC patients with BMs receiving first‐line osimertinib or first‐generation EGFR‐TKIs. Upfront CLT was defined as CLT performed before disease progression to the first‐line EGFR‐TKIs. Pattern of treatment failure and survival outcomes were extensively investigated. Among the 367 patients enrolled, first‐generation EGFR‐TKI was administered in 265, osimertinib in 102 and upfront CLT performed in 140. Patients receiving osimertinib had more ( P < .001) and larger BMs ( P = .003) than those receiving first‐generation EGFR‐TKIs. After propensity score matching, osimertinib was found to prolong OS (37.7 vs 22.2 months, P = .027). Pattern of failure analyses found that 51.8% of the patients without upfront CLT developed their initial progressive disease (PD) in the brain and 59.0% of the cranial PD occurred at the original sites alone, suggesting potential clinical value of upfront CLT. Indeed, upfront stereotactic radiosurgery (SRS) and/or surgery was associated with improved OS among those receiving first‐generation EGFR‐TKIs ( P = .019) and those receiving osimertinib ( P = .041). In summary, compared to first‐generation EGFR‐TKIs, osimertinib is associated with improved OS in untreated EGFR‐mutant NSCLC with BMs. Meanwhile, upfront SRS and/or surgery may provide extra survival benefit, which needs to be verified in future studies. Abstract : What's new? Nonsmall cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations is linked to frequent occurrence of brain metastasis. While existing treatments for brain metastasis are limited, a third‐generation EGFR tyrosine kinase inhibitor (TKI), osimertinib, may be of clinical value. Here, data from the FLAURA clinical study, in which osimertinib was compared against first‐generation EGFR‐TKIs in untreated EGFR‐mutant NSCLC patients with brain metastases, osimertinib demonstrated superior overall survival benefit. Patterns of treatment failure among patients offer a basis for optimizing cranial local therapy. Additional survival benefits may be gained by upfront neurosurgery/stereotactic radiosurgery in patients receiving first‐line osimertinib therapy.