Anlotinib Combined with Cranial Radiotherapy for Non-Small Cell Lung Cancer Patients with Brain Metastasis: A Retrospectively, Control Study

Abstract

Introduction

Cranial radiotherapy (CRT) is the main treatment for non-small cell lung cancer (NSCLC) with brain metastasis (BM) and non-EGFR/ALK/ROS1-TKIs indication, and anlotinib can improve overall prognosis. However, the clinical effects of CRT combined with anlotinib for the treatment of NSCLC with BM remain unclear.

Methods

We retrospectively analyzed the clinical effects of anlotinib + CRT versus CRT alone in NSCLC patients with BM and non-EGFR/ALK/ROS1-TKIs indication from September 2016 to June 2020. The progression-free survival (PFS) and overall survival (OS) of anlotinib + CRT versus CRT alone were analyzed. After evaluation of the clinical characteristics to generate a baseline, the independent prognostic factors for intracranial PFS (iPFS) and OS were subjected to univariate and multivariate analysis. Finally, subgroup analysis for iPFS and OS was performed to assess treatment effects using randomized stratification factors and stratified Cox proportional hazards models.

Results

This study included data for 73 patients with BM at baseline. Of the 73 patients, 45 patients received CRT alone, and 28 patients received CRT + anlotinib. There was no significant difference in clinical features between the two groups (P > 0.05). Compared with the CRT group, the combined group had longer iPFS (median iPFS [miPFS]: 3.0 months vs 11.0 months, P = 0.048). However, there were no significant differences in OS, extracranial PFS, and systemic PFS. For clinical features, univariate and multivariate analysis showed that the plus anlotinib treatment was an independent advantage predictor of iPFS (hazard ratio [HR] 0.51; 95% confidence interval [CI] 0.27–0.95; P = 0.04), and age ≥57 years (HR 1.04, 95% CI 1.01–1.08, P = 0.014) and KPS score ≤80 (HR 1.04, 95% CI 1.01–1.08, P = 0.014) were independent disadvantage predictors of OS (P < 0.05). In addition, although this difference was not statistically significant (p > 0.05), the patients with the anlotinib + local CRT (LCRT) treatment had the longest iPFS (miPFS: 27.0 months) and OS (median OS [mOS]: 36 months). The miPFS and mOS values for the LCRT group were 11 months and 18 months, respectively, with shorter values for whole-brain RT (WBRT) + anlotinib group, WBRT + LCRT + anlotinib group, WBRT, and WBRT + LCRT.

Conclusion

Anlotinib can improve the intracranial lesion control and survival prognosis of NSCLC patients with CRT.

Keywords:

• radiotherapy
• lung cancer
• brain metastases
• progression-free survival
• overall survival

Acknowledgments

The study was supported by the First Affiliated Hospital of Bengbu Medical College Science Fund for Distinguished Young Scholars (No. 2019BYYFYJQ04), the Natural Science Foundation of Bengbu Medical College (No. BYKY2019097ZD), the Bengbu Medical College Science Fund for “Excellent Young Teachers in 512 Talent Development Programme” (No. BY51201314), and the Bengbu – Bengbu Medical College Joint Research Project (No. BYLK201810).

Abbreviations

NSCLC, non-small cell lung cancer; BM, brain metastasis; mOS, median survival time; OS, survival time; TKIs, tyrosine kinase inhibitors; ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; ROS1, C-ros oncogene 1-receptor tyrosine kinase; CR, complete remission; mPFS, median progression-free survival; TTF, time to treatment failure; PFS, progression-free survival; BBB, blood–brain barrier; HR, hazard ratio; CI, confidence interval; ORR, objective response rate; TTBP, time to brain progression; CRT, cranial radiotherapy; KPS, Karnofsky Performance Status; UICC, Union for International Cancer Control; AJCC, American Joint Committee on Cancer; CT/MRI, computed tomography/magnetic resonance imaging; WBRT, whole-brain radiotherapy; RECIST, Response Evaluation Criteria in Solid Tumors; ORR, Overall response rate; PR, partial response; iPFS, intracranial progression-free survival; ePFS, extracranial progression-free survival; sPFS, Systematic progression-free survival; S.D, standard deviation; miPFS, median intracranial progression-free survival; mePFS, median extracranial progression-free survival; msPFS, median systematic progression-free survival.

Data Sharing Statement

The data used and/or analyzed in this study are available from the corresponding author upon reasonable request.

Ethics Approval and Consent to Participate

This study was a retrospective study, which utilized collected clinical data of patients, did not interfered with the treatment plan of patients, did not present physiological risks to patients, and maintained the privacy of patients. Some data were for patients who had died before this study. The ethics committee of the First Affiliated Hospital of Bengbu Medical College considered the risk-benefits and determined that informed consent was not required for this analysis. All processes conformed to the Declaration of Helsinki. The study design was reviewed and approved by the First Affiliated Hospital of Bengbu Medical College.

Disclosure

The authors report no conflicts of interest in this work.