Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.
Concurrent TP53 mutation adversely impact the efficacy of crizotinib in ROS1-rearranged lung cancer patients.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr e20535)
Author(s): Lin Gen, Huamin Xu, Jun Zhao, Jinliang Kong, Xinghao Ai, Fenglei Yu, Kaiqi Du, Lingjun Zhu, Lin Li, Hongxia Ma, Qiaoli Wang, Huanhuan Xiong, Rongrong Chen, Xuefeng Xia; Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China; Geneplus-Beijing Institute, Beijing, China; Beijing Cancer Hospital, Beijing, China; The First Affiliated Hospital of Guangxi Medical University, Nanning, China; Shanghai Chest Hospital, Shanghai, China; The Second Xiangya Hospital of Central South University, Changsha, China; Zhejiang Rongjun Hospital, Jiaxing, China; Jiangsu Province Hospital, Nanjing, China; Beijing Hospital, Beijing, China; Pneumology Department, The Affiliated Traditional Medical Hospital of Xinjiang Medical University, Urumqi, China
Background: ROS1 tyrosine kinase inhibitors (TKIs) are now standard of care for patients with advanced ROS1-rearranged NSCLC. But factors that may affect the efficacy of ROS1 TKIs remain to be explored. Methods: We conducted a retrospective multicenter study of lung cancer patients with ROS1 rearrangements. Treatment and survival follow-up was done and clinical records were reviewed. PFS distribution was analyzed by Kaplan-Meier method with log-rank test. Results: In total, we included 94 lung cancer patients with ROS1 fusion genes profiled by next-generation sequencing from May 2016 to September 2018. Fifty of them were female. The median diagnosis age was 54 (25-83). The most common histologic type was adenocarcinoma, which was confirmed in 75 of 78 patients with available pathological results. The most common fusion partners were CD74, EZR, SDC4 and SLC34A2 identified in 42, 19, 12 and 8 patients respectively. Concurrent actionable mutations were uncommon for ROS1 fusion-positive patients. The most frequent concomitant mutated gene was TP53, which was detected in 33% of all the patients. After excluding 29 patients who were lost to follow-up at the very start, the median follow-up time was 8.5 (0-28) months from the moment when mutation profiling was performed. Thirty-nine patients received treatment with crizotinib, among whom 27 were treatment-naïve patients. The median PFS of the 39 patients with crizotinib was not reached yet. Patients with baseline CNS metastasis tend to have shorter PFS compared to patients without (median, 12 vs NR, p = 0.0073). Besides, concurrent TP53 mutations were correlated with worse PFS (median, both NR, p = 0.0417). Mutation profiles of 10 patients were derived from ctDNA testing. No difference was found in PFS between these 10 patients with others whose genomic profiles were based on fresh tissue or FFPE specimens, suggesting that plasma ctDNA serves as good specimen source for mutation profiling to monitor clinical treatment. Conclusions: Concurrent TP53 mutation and presence of CNS metastasis are associated with decreased PFS of ROS1-positive patients treated with crizotinib.