Dong Zhi, Gao Jing, Gong Jifang, Li Jie, Li Yan, Wang Xicheng, Li Yanyan, Shen Lin, Li Jian
Department of Gastrointestinal Oncology, Peking University Cancer Hospital, Beijing 100142, China.
Zhonghua Wei Chang Wai Ke Za Zhi. 2016 Nov 25;19(11):1286-1289.
To evaluate the feasibility of imatinib reintroduction in gastrointestinal stromal tumor(GIST) with high recurrence risk after imatinib adjuvant therapy failure.
Clinical and follow-up data of 24 recurrent GIST patients with high recurrence risk receiving imatinib standard dose reintroduction(400 mg/d or 600 mg/d) after stopping imatinib adjuvant treatment more than 3 months in Department of GI Oncology of Peking University Cancer Hospital from August 2005 to January 2016 were retrospectively analyzed. The objective response rate(ORR), relapse-free survival(RFS) of imatinib reintroduction were evaluated and the difference of efficacy in patients receiving different imatinib adjuvant therapy duration were compared.
Of 24 patients, 21 were male and 3 were female. The median age was 53 years(39-72 years). Mutation detection of tumor tissues before imatinib therapy showed 20 patients had c-Kit exon 11 mutation,3 patients exon 9 mutation and 1 patient c-Kit/PDGFRA wild type mutation. The median recurrence time was 14 months in all the patients (95%CI:7.9-20.0) and in those patients receiving imatinib adjuvant therapy for 1 or 2 years (9 patients in each group, 95%CI:11.1-16.9 and 8.2-19.8 respectively). The median recurrence time of 3 patients receiving imatinib adjuvant therapy for 3 years was 24, 41 and 54 months respectively. Of 2 patients receiving imatinib adjuvant therapy for 5 years, the median recurrence time was 4 and 18 months. Only one patient received imatinib adjuvant therapy for 6 years, and the recurrence time was 6 months. Twenty patients with exon 11 mutation and 1 patient with wide type received imatinib treatment at a dose of 400 mg daily, and 3 patients with exon 9 mutation received the dosage of 600 mg per day. Among the patients receiving imatinib reintroduction, 11 patients(45.8%) got partial response(PR), 12 patients(50.0%) had stable disease and 1 patient had progression disease. The response rate in patients receiving imatinib adjuvant therapy for 1 year(6/9, 67%) was significantly higher than that in patients receiving adjuvant therapy for ≥2 years(3/15, 20%)(P=0.036). The median progression-free survival (PFS) of imatinib reintroduction was 31 months in all the patients(95%CI:23.6-38.4). The median PFS in patients receiving imatinib adjuvant therapy for 1 year(9 cases), 2 years (9 cases) and ≥3 years (6 cases) was 50 months(95%CI:27.3-72.7), 26 months(95%CI:10.7-41.3) and fall short of median PFS. No significant difference was observed among three groups(P=0.295).
Imatinib reintroduction is still effective to GIST after imatinib adjuvant therapy failure. The different imatinib adjuvant therapy duration can influence the benefit of imatinib reintroduction.
评估伊马替尼辅助治疗失败后,再次引入伊马替尼治疗高复发风险胃肠道间质瘤(GIST)的可行性。
回顾性分析2005年8月至2016年1月北京大学肿瘤医院胃肠肿瘤内科24例高复发风险的复发性GIST患者的临床及随访资料,这些患者在停用伊马替尼辅助治疗3个月以上后接受伊马替尼标准剂量再次引入治疗(400mg/d或600mg/d)。评估伊马替尼再次引入治疗的客观缓解率(ORR)、无复发生存期(RFS),并比较不同伊马替尼辅助治疗时长患者的疗效差异。
24例患者中,男性21例,女性3例。中位年龄为53岁(39 - 72岁)。伊马替尼治疗前肿瘤组织的突变检测显示,20例患者存在c-Kit外显子11突变,3例患者存在外显子9突变,1例患者为c-Kit/PDGFRA野生型突变。所有患者的中位复发时间为14个月(95%CI:7.9 - 20.0),接受伊马替尼辅助治疗1年或2年的患者(每组9例,95%CI分别为:11.1 - 16.9和8.2 - 19.8)。3例接受伊马替尼辅助治疗3年的患者,中位复发时间分别为24、41和54个月。2例接受伊马替尼辅助治疗5年的患者,中位复发时间分别为4和18个月。仅1例患者接受伊马替尼辅助治疗6年,复发时间为6个月。20例外显子11突变患者和1例野生型患者接受每日400mg伊马替尼治疗,3例外显子9突变患者接受每日600mg剂量治疗。接受伊马替尼再次引入治疗的患者中,11例(45.8%)获得部分缓解(PR),12例(50.0%)疾病稳定,1例疾病进展。接受伊马替尼辅助治疗1年的患者缓解率(6/9,67%)显著高于接受辅助治疗≥2年的患者(3/15,20%)(P = 0.036)。伊马替尼再次引入治疗的中位无进展生存期(PFS)在所有患者中为31个月(95%CI:23.6 - 38.4)。接受伊马替尼辅助治疗1年(9例)、2年(9例)和≥3年(6例)的患者,中位PFS分别为50个月(95%CI:27.3 - 72.7)、26个月(95%CI:10.7 - 41.3),未达到中位PFS。三组间差异无统计学意义(P = 0.295)。
伊马替尼辅助治疗失败后,再次引入伊马替尼治疗GIST仍然有效。不同的伊马替尼辅助治疗时长会影响再次引入伊马替尼治疗的获益。