Intrathecal pemetrexed improves survival outcomes in previously treated EGFR-mutant advanced non-small-cell lung cancer with leptomeningeal metastases
Liqun Li,
Zhe Huang,
Yangqian Chen,
Hongzhi Ma,
Xiaoquan Chen,
Huan Yan,
Haoyue Qin,
Yuda Zhang,
Xing Zhang,
Wenjuan Jiang,
Zhan Wang,
Lin Zhang,
Fanxu Zeng,
Zhiguo Zhou,
Xingxiang Pu,
Nong Yang,
Liang Zeng,
Yongchang Zhang
Affiliations
Liqun Li
Department of Medical Anesthesia, Pain Ward, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China; Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
Zhe Huang
Department of Medical Anesthesia, Pain Ward, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China; Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
Yangqian Chen
Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
Hongzhi Ma
Department of Radiotherapy, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, 410008, China
Xiaoquan Chen
Department of Medical Anesthesia, Pain Ward, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
Huan Yan
Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
Haoyue Qin
Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
Yuda Zhang
Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
Xing Zhang
Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
Wenjuan Jiang
Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
Zhan Wang
Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
Lin Zhang
Department of Radiotherapy, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, 410008, China
Fanxu Zeng
Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
Zhiguo Zhou
Department of Medical Anesthesia, Pain Ward, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
Xingxiang Pu
Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
Nong Yang
Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
Liang Zeng
Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China; Corresponding author.
Yongchang Zhang
Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China; Early Clinical Trials Center, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, 410008, China; Corresponding author. Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China.
Objective: This study assessed the impact of intrathecal pemetrexed (IP) in managing leptomeningeal metastases (LM) in previously treated patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC). Methods: We analyzed the clinical and survival outcomes of 50 patients with LM who received 50 mg IP after disease progression with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment between September 2021 and September 2023 at the Hunan Cancer Hospital. Treatment response was evaluated based on improvement in neurological symptoms/signs and Karnofsky Performance Status (KPS) scores. We also evaluated the overall survival (OS), intracranial progression-free survival (I-PFS), and extracranial progression-free survival (E-PFS). Next generation sequencing (NGS) was employed to explore the underlying mechanisms of LM after EGFR-TKIs resistance. Results: IP treatment was associated with a 64 % clinical response rate, median I-PFS of 5.3 months (95 % confidence intervals [CI], 1.4–9.2), E-PFS of 8.0 months (95 % CI, 2.2–13.8), and OS of 12.0 months (95 % CI, 9.6–14.4). Compared with non-responders, responders to IP demonstrated significantly prolonged I-PFS (11.2 months vs. 1.0 month; hazard ratio [HR]: 0.15, 95 % CI: 0.06–0.39), E-PFS (11.2 months vs. 3.0 months; HR: 0.24, 95 % CI: 0.10–0.57), and OS (15.5 months vs. 3.8 months; HR: 0.22, 95 % CI: 0.08–0.58) (all P < 0.001). Adverse events(AEs) primarily consisted of myelosuppression (54 %) and hepatic damage (24 %), but were manageable and did not result in any deaths. EGFR mutations were consistent between cerebrospinal fluid (CSF) and primary tumors in 100 % of cases. CSF also exhibited genetic variations such as EGFR mutations/amplifications and alterations in TP53, CDKN2A, MET, and CDK6. Conclusion: IP represents a potentially viable treatment option for managing LM in patients with EGFR-TKI-resistant EGFR-mutant advanced NSCLC. Clinical responses as measured by the improvement of neurological symptoms/signs and KPS scores were associated with favorable survival outcomes.
