Chengjuan Fan1, Qiuyu Zhao1, Li Li1, Weixi Shen1, Yang Du2, Chong Teng1, Feng Gao2, Xiaowei Song1, Qiuying Jiang1, Dayong Huang1, Yinghua Jin3, Yanju Lv1, Lingxiao Wei4, Tengfei Shi3, Xue Zhao1, Naisheng Gao1, Zhengjun Jiang1, Tao Xin5. 1. Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China. 2. Department of Oncology, The Second Tumor Hospital of Heilongjiang Province, Harbin, People's Republic of China. 3. Department of Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China. 4. Department of Oncology, Yunnan Cancer Hospital, Kunming, People's Republic of China. 5. Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China. Electronic address: xintao1234@263.net.
Abstract
INTRODUCTION: We aimed to evaluate the efficacy and safety of intrathecal pemetrexed (IP) for treating EGFR-mutant leptomeningeal metastases (LMs) from EGFR-mutant NSCLC. METHODS: Patients with EGFR-mutant NSCLC with LM who had failed tyrosine kinase inhibitors were recruited. The dose of IP was escalated from 15 mg to 80 mg using an accelerated titration design in a phase 1 study. The recommended dose (RD) determined in phase 1 was used in the phase 2 study. The primary end point was treatment efficacy measured as the clinical response rate. Overall survival and adverse events (AEs) were evaluated as secondary end points. RESULTS: The RD observed in the phase 1 study was 50 mg pemetrexed. A total of 30 cases of LM-NSCLC were enrolled in the phase 2 study, including 14 males and 16 females. Four patients did not survive for 4 weeks and could not be evaluated for efficacy. The clinical response rate was 84.6% (22 of 26). The median overall survival of all patients was 9.0 months (n = 30, 95% confidence interval: 6.6-11.4 mo). Most AEs were mild, and the most frequent AE of any grade was myelosuppression (n = 9, 30%), which returned to normal after symptomatic treatment. CONCLUSIONS: This study revealed that 50 mg pemetrexed is the RD which results in few AEs and a good response rate. IP is an effective treatment for patients with EGFR-mutant NSCLC-LM who had failed on tyrosine kinase inhibitor.
INTRODUCTION: We aimed to evaluate the efficacy and safety of intrathecal pemetrexed (IP) for treating EGFR-mutant leptomeningeal metastases (LMs) from EGFR-mutant NSCLC. METHODS: Patients with EGFR-mutant NSCLC with LM who had failed tyrosine kinase inhibitors were recruited. The dose of IP was escalated from 15 mg to 80 mg using an accelerated titration design in a phase 1 study. The recommended dose (RD) determined in phase 1 was used in the phase 2 study. The primary end point was treatment efficacy measured as the clinical response rate. Overall survival and adverse events (AEs) were evaluated as secondary end points. RESULTS: The RD observed in the phase 1 study was 50 mg pemetrexed. A total of 30 cases of LM-NSCLC were enrolled in the phase 2 study, including 14 males and 16 females. Four patients did not survive for 4 weeks and could not be evaluated for efficacy. The clinical response rate was 84.6% (22 of 26). The median overall survival of all patients was 9.0 months (n = 30, 95% confidence interval: 6.6-11.4 mo). Most AEs were mild, and the most frequent AE of any grade was myelosuppression (n = 9, 30%), which returned to normal after symptomatic treatment. CONCLUSIONS: This study revealed that 50 mg pemetrexed is the RD which results in few AEs and a good response rate. IP is an effective treatment for patients with EGFR-mutant NSCLC-LM who had failed on tyrosine kinase inhibitor.
Authors: Rimas V Lukas; Jigisha P Thakkar; Massimo Cristofanilli; Sunandana Chandra; Jeffrey A Sosman; Jyoti D Patel; Priya Kumthekar; Roger Stupp; Maciej S Lesniak Journal: J Neurooncol Date: 2022-01-20 Impact factor: 4.130