三阴性乳腺癌含抗体偶联药物治疗方案的临床研究解析

Analysis of clinical trials of antibody-drug conjugated for triple-negative breast cancer

目的解析关于三阴性乳腺癌(TNBC)含抗体偶联药物(ADC)治疗方案临床研究的进行情况和结果。方法检索http://clinicaltrials.gov/网站有关TNBC含ADC治疗方案的临床研究,时间截止2023年2月。结果共检索相关临床研究17项,其中靶向人滋养细胞表面糖蛋白抗原2(Trop-2)的研究8项(sacituzumab govitecan 4项,datopotamab deruxtecan 3项,SKB2641项),靶向人表皮生长因子受体2(HER 2)的研究4项(trastuzumab deruxtecan 2,trastuzumab duocarmazine 2项),靶向受体酪氨酸激酶样孤儿受体(ROR)1、ROR2、糖蛋白非转移性黑色素瘤蛋白B(gpNMB)、肾上腺素A4(EFNA4)、LIV-1的研究各1项(NBE-002,CAB-ROR2-ADC,glembatumumab vedotin,PF-06647263,ladiratuzumab vedotin)。17项研究中只有6项(NCT03734029、NCT02277717、NCT01997333、NCT02078752、NCT01631552和NCT02574455)已完成并有研究结果。NCT03734029研究结果提示与其他治疗方案相比,trastuzumab deruxtecan能显著延长HER2低表达乳腺癌患者的中位无进展生存期(mPFS)和总生存期(OS)(P<0.01)。NCT02277717研究表明进行单药trastuzumab duocarmazine治疗的晚期实体瘤患者中,HER2低表达乳腺癌和TNBC的缓解率分别为27%和40%,PFS分别为4.1个月和4.4个月。NCT01631552研究显示sacituzumab govitecan单药对晚期TNBC患者的客观缓解率为33.3%。ASCENT试验(NCT02574455)研究结果显示sacituzumab govitecan能显著延长晚期TNBC患者的PFS和OS。而在METRIC试验中,TNBC患者使用glembatumumab vedotin后只能获得有限的生存优势。同样,NCT02078752研究也提示了PF-06647263在TNBC患者中有限的抗肿瘤活性。结论ADC治疗在TNBC,尤其是晚期TNBC中显示出一定的临床获益,但更精准、安全的治疗方案还需要通过更多研究来探索和证实。

Objective To analyze the conduct and results of clinical trials on antibody-drug conjugates(ADC)in the treatment of triple-negative breast cancer(TNBC).Methods The clinical trials on TNBC containing ADC treatment regimens were searched on the website(http://clinicaltrials.govas/).Search deadline was February 2023.Results Of 17 relevant clinical trials,there were 8 clinical trials of targeting human trophoblast cell surface glycoprotein antigen 2(Trop-2),including sacituzumab govitecan(4),datopotamab deruxtecan(3)and SKB264(1);Four trials of targeting human epidermal growth factor receptor 2(HER2)-related trials,including trastuzumab deruxtecan(2)and trastuzumab duocarmazine(2);Targeting receptor tyrosine kinase-like orphan receptor(ROR)1,ROR2,glycoprotein non metastatic melanoma protein B(gpNMB),adrenaline A4(EFNA4)and LIV-1,each with one trial(NBE-002,CAB-ROR2-ADC,glembatumumab vedotin,PF-06647263,ladiratuzumab vedotin).Only 6 of the 17 trials(NCT03734029,NCT02277717,NCT01997333,NCT02078752,NCT01631552 and NCT02574455)have been completed with research results.The results of NCT03734029 suggested that trastuzumab deruxtecan can significantly prolong the mediam progression-free survival(mPFS)and overall survival(OS)of breast cancer patients with HER2-low expression(P<0.01).NCT02277717 trial showed that in the patients with advanced solid tumors treated with single agent trastuzumab duocarmazine the remission rates were 27%in patients with HER2-low expression and 40%in TNBC patients,and PFS were 4.1 months and 4.4 months,respectively.NCT01631552 trial showed that the objective response rate was 33.3%in the patients with advanced TNBC treated with sacituzumab govitecan monotherapy.NCT02574455(ASCENT trial)showed that sacituzumab govitecan can significantly prolong PFS and OS in the patients with advanced TNBC.METRIC trial suggested that the patients with TNBC only obtained a limited survival advantage after using glembatumumab vedotin.NCT02078752 trial also suggested limited antitumor activity of PF-06647263 in patients with TNBC.Conclusion ADC therapy has certain clinical benefits in TNBC,especially advanced TNBC,but more accurate and safe treatment options need to be explored and confirmed by more clinical trials.