Analysis of the benefit of sequential cranial radiotherapy in patients with EGFR mutant non-small cell lung cancer and brain metastasis

Abstract

Although cranial radiotherapy is considered the standard treatment for brain metastasis (BM), EGFR tyrosine kinase inhibitors (TKIs) have shown promising activity in EGFR mutant non-small cell lung cancer (NSCLC) patients with BM. However, the efficacy of sequential cranial radiotherapy in patients with EGFR mutant NSCLC who are treated with EGFR TKIs remains to be determined. Patients with NSCLC who harbored an EGFR mutation and whose BM had been treated with EGFR TKIs were retrospectively reviewed. The clinical outcomes of patients treated with EGFR TKIs alone and those treated with cranial radiotherapy followed by EGFR TKIs (additive therapy) were compared. Of the 573 patients with NSCLC with BM who harbored an EGFR mutation and had received EGFR TKIs, 121 (21.1 %) had BM at the time of initial diagnosis. Fifty-nine (49 %) patients were treated with additive therapy, whereas 62 (51 %) patients were treated only with EGFR TKIs. No significant differences were observed between the additive therapy group and the EGFR TKI alone group regarding intracranial progression-free survival (PFS) (16.6 vs 21.0 months, p = 0.492) or extracranial PFS (12.9 vs 15.0 months, p = 0.770). The 3-year survival rates were similar in both groups (71.9 vs 68.2 %, p = 0.675). Additive therapy consisting of cranial radiotherapy followed by EGFR TKI treatment did not improve OS or intracranial PFS compared with EGFR TKI treatment alone in EGFR mutant NSCLC patients with BM. Further prospective studies are needed to determine the precise benefits of sequential cranial radiotherapy in EGFR mutant NSCLC treated with EGFR TKIs.Keywords Non-small cell lung cancer (NSCLC) Á Brain metastasis Á Epidermal growth factor receptor (EGFR) Á Tyrosine kinase inhibitor (TKI) Á Whole brain radiation therapy (WBRT) Á Stereotactic radiosurgery (SRS)

Management and Outcomes of Newly Diagnosed Non-Small Cell Lung Cancer Patients with Brain Metastases: A Real-World Study in Japan

“…Patients who received best supportive care alone were excluded from this analysis. was no significant difference in OS according to the type of initial treatment (local vs. systemic) for patients with a driver mutation in our study, and similar results have been reported by several retrospective studies comparing upfront radiotherapy and EGFR-TKI for NSCLC patients with an EGFR mutation [17][18][19]. In contrast, Magnuson et al [20] reported that the use of upfront EGFR-TKI was associated with an inferior OS compared with upfront radiotherapy.…”

A Neuro-oncologist’s Perspective on Management of Brain Metastases in Patients with EGFR Mutant Non-small Cell Lung Cancer

“…Subsequent studies in EGFRact+ patients have demonstrated a RR of 87.8% as monotherapy with overall survival (OS) 21.9 months [23••]. Gefitinib is the most common first line TKI in Asian countries and retrospective studies of EGFRact+ enriched populations have supported the use of TKIs as monotherapy without radiation [24, 25•, 26]. …”

“…Small studies examining the use of TKIs and WBRT have provided conflicting results and it remains unclear if addition of TKI to radiotherapy improved survival [81] or could possibly have deleterious effects [82]. In contrast, clinical trials have reported that patients were limited in receiving subsequent systemic treatment due to deteriorations in performance status after WBRT [26]. Meta-analysis also confirms more side effects with radiotherapy compared to TKIs alone [83•].…”

New treatment options and challenges for patients with anaplastic lymphoma kinase-positive non-small cell lung cancer with brain metastases

“…Also, the choice of SRS, alectinib, or both has yet to be delineated in prospective trials. In patients harboring an EGFR mutation, the addition of TKI therapy to SRS or WBRT has so far met with mixed results (22)(23)(24). The possibility of treating with alectinib first and using SRS for lesions that persist after therapy remains an option that has not been tested.…”