背景:免疫检查点抑制剂(ICIs)在新辅助和辅助环境中的长期生存益处对于具有错配修复缺陷(dMMR)或微卫星不稳定性高(MSI-H)的结直肠癌(CRC)和胃癌(GC)尚不清楚。
方法:这项回顾性研究纳入了接受至少一剂新辅助ICIs(新辅助队列,NAC)或佐剂ICIs(佐剂队列,AC)在中国的17个中心。如果所有肿瘤病变均可彻底切除,则IV期疾病患者也符合资格。
结果:在NAC(n=124)中,客观反应率分别为75.7%和55.4%,分别,在CRC和GC中,病理完全缓解率分别为73.4%和47.7%,分别。3年无病生存率(DFS)和总生存率(OS)分别为96%(95CI90-100%)和CRC的100%(中位随访时间[mFU]29.4个月),分别,GC(MFU33.0个月)分别为84%(72-96%)和93%(85-100%),分别。在AC(n=48)中,3年DFS和OS率为94%(84-100%),CRC(MFU35.5个月)为100%,分别,GC(MFU40.4个月)分别为92%(82-100%)和96%(88-100%),分别。在7名远处复发的患者中,4人接受了PD1和CTLA4联合或不联合化疗和靶向药物的双重阻断,有三个部分反应和一个进行性疾病。
结论:经过相对较长的随访,这项研究表明,在dMMR/MSI-HCRC和GC中,新佐剂和佐剂ICIs可能都与有希望的DFS和OS有关,这应该在进一步的随机临床试验中得到证实。
BACKGROUND: The long-term survival benefit of immune checkpoint inhibitors (ICIs) in neoadjuvant and adjuvant settings is unclear for colorectal cancers (CRC) and gastric cancers (GC) with deficiency of mismatch repair (dMMR) or microsatellite instability-high (MSI-H).
METHODS: This retrospective study enrolled patients with dMMR/MSI-H CRC and GC who received at least one dose of neoadjuvant ICIs (neoadjuvant cohort, NAC) or adjuvant ICIs (adjuvant cohort, AC) at 17 centers in China. Patients with stage IV disease were also eligible if all tumor lesions were radically resectable.
RESULTS: In NAC (n = 124), objective response rates were 75.7% and 55.4%, respectively, in CRC and GC, and pathological complete response rates were 73.4% and 47.7%, respectively. The 3-year disease-free survival (DFS) and overall survival (OS) rates were 96% (95%CI 90-100%) and 100% for CRC (median follow-up [mFU] 29.4 months), respectively, and were 84% (72-96%) and 93% (85-100%) for GC (mFU 33.0 months), respectively. In AC (n = 48), the 3-year DFS and OS rates were 94% (84-100%) and 100% for CRC (mFU 35.5 months), respectively, and were 92% (82-100%) and 96% (88-100%) for GC (mFU 40.4 months), respectively. Among the seven patients with distant relapse, four received dual blockade of PD1 and CTLA4 combined with or without chemo- and targeted drugs, with three partial response and one progressive disease.
CONCLUSIONS: With a relatively long follow-up, this study demonstrated that neoadjuvant and adjuvant ICIs might be both associated with promising DFS and OS in dMMR/MSI-H CRC and GC, which should be confirmed in further randomized clinical trials.