The optimal therapy strategy for epidermal growth factor receptor‐mutated non‐small cell lung cancer patients with brain metastasis: A real‐world study from Taiwan

Abstract

Background: The treatment options for epidermal growth factor receptor (EGFR)mutated non-small cell lung cancer (NSCLC) with brain metastases (BMs) include EGFR-tyrosine kinase inhibitors (TKIs), stereotactic radiosurgery (SRS), whole-brain radiotherapy, brain surgery, and antiangiogenesis therapy. As treatment options evolve, redefining optimal treatment strategies to improve survival are crucial. Methods: A total of 150 EGFR-mutant NSCLC patients with BMs who received firstor second-generation EGFR-TKIs as first-line treatment between January 2012 and October 2019 were included in this analysis. Results: After multivariate analysis, patients with the graded prognostic assessment for lung cancer using molecular markers (Lung-mol GPA) ≥3 (hazard ratio [HR]: 0.538, 95% confidence interval [CI]: 0.35-0.83), who received afatinib or erlotinib as first-line treatment (HR: 0.521, 95% CI: 0.33-0.82), underwent SRS therapy (HR: 0.531, 95% CI: 0.32-0.87), or were sequentially treated with osimertinib (HR: 0.400, 95% CI: 0.23-0.71) were associated with improved overall survival (OS). Furthermore, SRS plus EGFR-TKI provided more OS benefits in patients with Lung-mol GPA ≥3 compared with EGFR-TKI alone in our patient cohort (44.9 vs. 26.7 months, p = 0.005). The OS in patients who received sequential osimertinib therapy was significantly longer than those without osimertinib treatment (43.5 vs. 24.3 months, p < 0.001), regardless of T790 mutation status (positive vs. negative vs. unknown: 40.4 vs. 54.6 vs.43.4 months, p = 0.227). Conclusions:The study demonstrated that EGFR-mutant NSCLC patients with BMs could be precisely treated with SRS according to Lung-mol GPA ≥3. Sequential osimertinib was associated with prolonged survival, regardless of T790M status.K E Y W O R D S brain metastasis, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors, graded prognostic assessment for lung cancer using molecular markers (lung-mol GPA), stereotactic radiosurgery

Different Tyrosine Kinase Inhibitors Used in Treating EGFR-Mutant Pulmonary Adenocarcinoma with Brain Metastasis and Intracranial Intervention Have No Impact on Clinical Outcomes

“…The lung-molGPA has six factors, with total scores ranging from 0 to 4. Cheng et al examined the effects of lung-molGPA and different treatment strategies on survival of EGFR-mutant NSCLC patients with brain metastasis; a lung-molGPA of ≥3 was associated with improved OS [46]. In our study, GPA versions 2017 and 2022 appropriately stratified patients with different OS, while patients with higher GPA scores (≥2.5 by version 2017 and ≥3 by version 2022) had significantly longer OS.…”

First-line treatment with TKI plus brain radiotherapy versus TKI alone in EGFR-mutated non-small cell Lung cancer with brain metastases: a systematic review and meta-analysis

“…In a retrospective study of patients with NSCLC with ≤ 3 BMs and EGFR-sensitive mutation [ 33 ], SRS + EGFR-TKIs was associated with significantly longer median OS compared to WBRT + EGFR-TKIs. In another retrospective study assessing the optimal treatment strategy for EGFR-mutant NSCLC with BMs [ 45 ], EGFR-TKIs plus SRS significantly improved OS compared to EGFR-TKI without SRS for patients with Lung-mol graded prognostic assessment (GPA) ≥ 3 but not for those with Lung-mol GPA < 3. In addition, no significant difference in OS was observed between EGFR-TKI with and without WBRT.…”

“…These results suggest that first-line SRS plus EGFR-TKIs is more effective than WBRT plus EGFR-TKIs. Nevertheless, SRS is likely limited by the number of intracranial lesions [ 33 ] or Lung-mol GPA score [ 45 ]. For patients with more BM lesions or low Lung-mol GPA scores, the superiority of SRS requires further evaluation.…”

“…However, the addition of brain RT to osimertinib treatment failed to prolong PFS and OS in another retrospective study [ 52 ]. In addition, Cheng et al [ 45 ] found that patients receiving first-line first- or secondgeneration EGFR-TKIs with sequential osimertinib had significantly longer survival than those without sequential osimertinib, regardless of the use of brain RT. Collectively, the value of upfront brain RT in the era of first-line osimertinib treatment requires further exploration.…”

Recent advances progress of targeted drugs combined with radiotherapy for advanced non-small cell lung cancer: a review

“…From this, it can be seen that Afatinib combined with brain radiation therapy may replace the first-generation EGFR-TKI single drug first-line treatment and become a new choice for NSCLC patients with EGFR mutations and brain metastases. In another retrospective study, Afatinib combined with stereotactic radiosurgery (SRS) can significantly improve the OS of patients with EGFR mutant NSCLC (lung mol GPA ≥ 3) with brain metastasis ( 29 ). In conclusion, the efficacy of Afatinib combined with intracranial radiotherapy needs to be further verified by special clinical trials.…”