Ⅲ期恶性黑色素瘤患者术后辅助抗PD-1 vs靶向治疗:中国多中心真实世界数据分析

Adjuvant therapy with anti-PD-1 antibody vs targeted therapy for patients with resected stageⅢmalignant melanoma:a real-world data analysis from China centers

背景与目的:众多的临床试验结果表明,抗程序性死亡[蛋白]-1(programmed death-1,PD-1)治疗及靶向治疗均可显著延长Ⅲ期恶性黑色素瘤患者术后的无复发生存时间(recurrence-free survival,RFS)。然而,抗PD-1辅助治疗在中国真实世界中的治疗效果尚未见文献报道。本研究旨在总结分析中国Ⅲ期恶性黑色素瘤患者术后接受抗PD-1辅助治疗的RFS,并与BRAFV600抑制剂vemurafenib进行初步对比分析。方法:回顾性分析2018年8月30日—2020年8月30日来自中国3所癌症中心的120例已经切除的Ⅲ期恶性黑色素瘤患者的临床信息。这些患者都接受了术后辅助性的pembrolizumab/toripalimab或vemurafenib治疗。采用Kaplan-Meier曲线评估RFS,采用log-rank检验来判断差异是否有统计学意义。结果:在接受辅助性抗PD-1治疗的90例Ⅲ期恶性黑色素瘤患者中,中位RFS(median-RFS,mRFS)为16个月(95%CI:14~18个月);12个月RFS率为69.5%(95%CI:64.6%~74.4%),24个月RFS率为45.8%(95%CI:40.5%~51.1%)。30例接受vemurafenib治疗的Ⅲ期恶性黑色素瘤患者中,mRFS为18个月(95%CI:10~21个月),12个月RFS率为62.8%(95%CI:54.0%~71.6%),24个月RFS率为35.9%(95%CI:27.1%~44.7%)。分层分析初步结果显示,抗PD-1治疗组和vemurafenib组的RFS没有明显差异。其次,BRAFV600E是否突变可能不影响抗PD-1治疗的RFS。另外,在本研究中,对于BRAFV600E突变的患者,术后接受抗PD-1治疗或vemurafenib,其RFS差异无统计学意义。最后,虽然皮肤型恶性黑色素瘤患者的RFS优于肢端型患者,来源不明患者的RFS最差,但在中国真实世界中,抗PD-1辅助治疗的治疗效果仍较差。结论:作为中国Ⅲ期恶性黑色素瘤患者辅助抗PD-1治疗的真实世界数据,在本研究中,辅助性抗PD-1治疗与辅助vemurafenib治疗效果的差异并无统计学意义,提示对于中国Ⅲ期恶性黑色素瘤患者,我们可能仍然需要探索更多的联合治疗来改善其辅助治疗的效果。

Background and purpose:Anti-programmed death-1(anti-PD-1)adjuvant therapy and targeted therapy have resulted in longer recurrence-free survival(RFS)for malignant melanoma patients in clinical trials.However,the efficacy of adjuvant anti-PD-1therapy in Chinese melanoma patients has not been previously reported.The purpose of this study was to retrospectively analyze the RFS in Chinese resected stageⅢmalignant melanoma patients treated with adjuvant anti-PD-1 therapy and to preliminarily compare it with BRAFV600 inhibitor vemurafenib.Methods:This study retrospectively collected the information of 120 patients with resected stageⅢmalignant melanoma from three major cancer centers in China from August 30,2018 to August 30,2020.These patients received adjuvant pembrolizumab/toripalimab or vemurafenib.RFS rates were assessed by Kaplan-Meier curves and log-rank tests were used to examined differences.Results:Among the 90 patients with stageⅢmalignant melanoma receiving adjuvant anti-PD-1 therapy,the median-RFS(mRFS)was 16 months(95%CI:14-18 months);the 12-month RFS rate was 69.5%(95%CI:64.6%-74.4%)and the 24-month RFS rate was 45.8%(95%CI:40.5%-51.1%).The mRFS for 30 patients who received vemurafenib was 18 months(95%CI:10-21 months),the 12-month RFS rate was 62.8%(95%CI:54.0%-71.6%),and the 24-month RFS rate was 32.9%(95%CI:27.1%-44.7%).In the stratified analysis,firstly,there was no difference in RFS between anti-PD-1 therapy group and vemurafenib group.Secondly,the BRAFV600Emutation status may did not affect the RFS of anti-PD-1 therapy.In addition,in this study,for the patients with BRAFV600Emutation,the RFS showed no difference between these patients received anti-PD-1 therapy or vemurafenib.Finally,although the RFS was better in patients with cutaneous melanoma than in patients with acral and worst in patients of unknown origin,the data for adjuvant therapy in China were still poor.Conclusion:These are the real-world data from adjuvant anti-PD-1 therapy in patients with resected stageⅢcutaneous and acral melanoma patients in China.In our study,adjuvant anti-PD-1 therapy is indistinguishable from vemurafenib indicates more combination therapies are needed to improve outcome in China.