J Cancer 2021; 12(5):1467-1473. doi:10.7150/jca.51411

Research Paper

A real-world study in advanced non-small cell lung cancer with de novo brain metastasis

Lei Lei1#, Wen-xian Wang1#, Dong Wang2#, Li Lin3, You-cai Zhu4, Hong Wang5, Li-ping Wang6, Wu Zhuang7, Mei-yu Fang1, Bing Wan8✉, Hui-jing Feng9✉, Chun-wei Xu2✉

1. Department of Chemotherapy, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou Zhejiang 310022, People's Republic of China
2. Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, People's Republic of China
3. Department of Oncology, Peking University International Hospital, Beijing 102206, People's Republic of China
4. Department of Thoracic Disease Center, Zhejiang Rongjun Hospital, Jiaxing Zhejiang 314000, People's Republic of China
5. Department of Lung Cancer, The Fifth Medical Center, General Hospital of PLA, Beijing 100071, People's Republic of China
6. Department of Thoracic Oncology, Baotou Cancer Hospital, Baotou Inner Mongolia 014000, People's Republic of China
7. Department of Medical Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou Fujian 350014, People's Republic of China
8. Department of Respiratory, The Affiliated Jiangning Hopsital of Nanjing Medical University, Nanjing Jiangsu 210002, People's Republic of China
9. Department of Thoracic Oncology, Shanxi Academy of Medical Sciences, Shanxi Bethune Hospital, Taiyuan Shanxi 030032, People's Republic of China
#Equal contributors

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Citation:
Lei L, Wang Wx, Wang D, Lin L, Zhu Yc, Wang H, Wang Lp, Zhuang W, Fang My, Wan B, Feng Hj, Xu Cw. A real-world study in advanced non-small cell lung cancer with de novo brain metastasis. J Cancer 2021; 12(5):1467-1473. doi:10.7150/jca.51411. Available from https://www.jcancer.org/v12p1467.htm

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Abstract

Brain metastases are the major cause of life-expectancy shortened for patients with lung cancer. The prognostic value of EGFR mutation subtypes and survival benefit of EGFR-tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC) patients with de novo brain metastasis is still not clear. Here, we present a real-world study nation-wide focusing on the prognostic value of genomic and therapeutic factors in overall survival (OS) of those patients. We enrolled a total of 233 patients diagnosed with advanced NSCLC and de novo BM from multi-medical centers across China. The enrolled patients were divided into 4 groups, including EGFR 19del, EGFR L858R, EGFR wild-type, and EGFR unknown groups. The median OS of patients with EGFR mutations and all patients were 29.0 and 25.0 months, respectively. There was significant difference in OS of patients among EGFR 19del (n=76), EGFR L858R (n=94), EGFR wild-type (n=46) and EGFR unknown (n=17) groups (30.5 vs 27.5 vs 16.0 vs 25.0, P=0.025). Patients treated by icotinib showed better OS than gefitinib and erlotinib (31.0 vs 25.5 vs 26.5, P=0.02). There was a difference in OS of patients received the whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or WBRT+SRS (20.0 vs 31.0 vs 30.0 months, P<0.001), respectively. In multivariate analysis, patients treated with icotinib had superior iPFS benefit than gefitinib and erlotinib (HR=0.86[95%CI (0.74-1.0)], P=0.04). Besides, the histology of non-adenocarcinomas, the number of BM (>3), and extracranial metastases status could have an independent negative impact on the OS of all patients (P<0.001). EGFR mutant NSCLC patients with de novo BM had a better OS than patients with EGFR wild type. Patients treated with icotinib had longer iPFS than gefitinib and erlotinib but not in OS. Non-adenocarcinomas, number of BM (>3) and extracranial metastases were independent negative prognostic factors in iPFS and OS of all patients. Prospective clinical trials are warranted to explore more effective multimodality in this population.

Keywords: de novo brain metastasis, EGFR, EGFR-tyrosine kinase inhibitors (TKIs), non-small-cell lung cancer