Erlotinib Versus Radiation Therapy for Brain Metastases in Patients With EGFR-Mutant Lung Adenocarcinoma

Abstract

Purpose/Objectives Radiation therapy (RT) is the principal modality in the treatment of patients with brain metastases (BM). However, given the activity of EGFR tyrosine kinase inhibitors in the central nervous system (CNS), it is uncertain whether upfront brain RT is necessary for patients with EGFR-mutant lung adenocarcinoma with BM. Methods and Materials Patients with EGFR-mutant lung adenocarcinoma and newly diagnosed BM were identified. Results 222 patients were identified. Exclusion criteria included prior erlotinib use, presence of a de novo erlotinib resistance mutation, or incomplete data. Of the remaining 110 patients, 63 were treated with erlotinib, 32 with whole-brain RT (WBRT), and 15 with stereotactic radiosurgery (SRS). Median OS for the whole cohort was 33 months. There was no significant difference in OS between the WBRT and erlotinib groups (median 35 vs. 26 months, p = .62), while patients treated with SRS had a longer OS compared with the erlotinib group (median, 64 months, p = .004). Median time to ICP was 17 months. There was a longer time to ICP in patients who received WBRT vs. erlotinib upfront (median 24 vs. 16 months, p = .04). Patients in the erlotinib or SRS group were more likely to fail intracranially as a component of first failure, while WBRT patients were more likely to fail outside the brain (p = .004). Conclusions The survival of patients with EGFR-mutant adenocarcinoma with BM is notably long, whether they receive upfront erlotinib or brain RT. We observed longer intracranial control with WBRT, even though the WBRT patients had a higher burden of intracranial disease. Despite the equivalent survival between the WBRT and erlotinib group, this study underscores the role of WBRT in producing durable intracranial control in comparison to a targeted biologic agent with known CNS activity.

Radiotherapy and Tyrosine Kinase Inhibitors in Stage IV Non-small Cell Lung Cancer: Real-life Experience

“…Better local control was found in both groups treated with upfront RT. In the WBRT group, the administration of erlotinib within 2 months of WBRT was associated with improved intracranial control on univariate analysis (23). A recent publication compared treatment outcomes between TKI monotherapy versus RT plus TKIs in a cohort of 133 patients with a diagnosis of stage IV NSCLC with brain metastasis, finding a better median intracranial PFS (16.0 vs. 11.5 months, p=0.017) and a better OS (22 vs. 15 months p=0.015) in the RT plus TKI group.…”

EGFR inhibition in NSCLC: New findings…. and opened questions?

“…Stereotactic radiosurgery (SRS) and whole brain radiotherapy (WBRT) concomitantly or followed by EGFR-TKIs remain the current gold standard for patients with BM, even if they are often associated with considerable adverse neurotoxicity and questionable efficacy. Activity of upfront first-generation EGFR-TKIs has been reported in retrospective series including low number of EastAsian patients (Park et al, 2012;Iuchi et al, 2013;Gerber et al, 2014;Zhang et al, 2016a), overall showing poor response rates likely due to the low penetration of such agents across the bloodbrain barrier (BBB) (Zhao et al, 2013;de Vries et al, 2012). Some studies showed that erlotinib has a better central nervous system (CNS) penetration than gefitinib (Togashi et al, 2012), thus suggesting that it could be preferred if TKI monotherapy is used upfront for asymptomatic patients with BM.…”

The Rationale for Targeted Therapies and Stereotactic Radiosurgery in the Treatment of Brain Metastases

“…Agents of this class can be used in first-line treatment of metastatic patients. Gerber et al found equivalent survival in lung cancer patients with brain metastases treated with upfront erlotinib versus standard-of-care whole-brain radiation therapy [55]. Although RTOG 0320 found a potentially deleterious effect to combination SRS and erlotinib, Welsh et al found no significant additional neurotoxicity in a phase II study that added erlotinib to whole brain RT.The overall response rate was 86%.…”