Men Qianqian, Duan Yinghua, Pei Fengyun, Yao Qijun, He Wan, Zhao Yandong, Shi Lishuo, Liu Guangjian, Huang Jun
Graceland Medical Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Department of Traditional Chinese Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
J Gastrointest Oncol. 2024 Aug 31;15(4):1534-1544. doi: 10.21037/jgo-23-940. Epub 2024 Aug 12.
BACKGROUND: Single-agent immunotherapy is less effective in patients with DNA mismatch repair-proficient/microsatellite stable (pMMR/MSS) metastatic colorectal cancer (mCRC). Whether pMMR/MSS mCRC patients benefit from combination immunotherapy remains unclear. This study aimed to evaluate the efficacy and safety of anti-programmed cell death protein 1 (PD-1) therapy combined with chemotherapy and bevacizumab in pMMR/MSS colorectal liver metastases (CRLM) patients. METHODS: A total of 12 patients with pMMR/MSS CRLM treated at The Sixth Affiliated Hospital of Sun Yat-sen University were enrolled. All patients were treated with at least 4 doses of PD-1 monoclonal antibody combined with chemotherapy and bevacizumab as neoadjuvant/adjuvant therapy. RESULTS: A total of 10 of the 12 patients received the combined therapies before primary tumor resection; the disease control rate (DCR) was 100% (10/10), and the objective response rate (ORR) was 70% (7/10). The ORR of liver metastases was 75% (9/12). Pathological complete response (pCR) was achieved in 1 primary tumor patient and 2 patients with hepatic lesions. A total of 5 patients underwent simultaneous resection of the primary tumor and liver metastases; 9 patients underwent microwave ablation for liver metastases. A total of 7 patients were assessed as having no evidence of disease (NED) with a median progression-free survival (PFS) interval of 9.2 (1.5-15.8) months after multimodality treatments for both primary and metastatic lesions. No severe immune-related adverse events (irAEs) and operational complications were observed. CONCLUSIONS: PD-1 blockade combined with chemotherapy and bevacizumab might be safe and effective for patients with pMMR/MSS CRLM. This treatment strategy might lead to better tumor regression and a higher chance of achieving NED.
背景:单药免疫疗法对DNA错配修复功能正常/微卫星稳定(pMMR/MSS)的转移性结直肠癌(mCRC)患者疗效较差。pMMR/MSS mCRC患者是否能从联合免疫疗法中获益仍不清楚。本研究旨在评估抗程序性细胞死亡蛋白1(PD-1)疗法联合化疗和贝伐单抗治疗pMMR/MSS结直肠癌肝转移(CRLM)患者的疗效和安全性。 方法:中山大学附属第六医院共纳入12例pMMR/MSS CRLM患者。所有患者均接受至少4剂PD-1单克隆抗体联合化疗和贝伐单抗作为新辅助/辅助治疗。 结果:12例患者中有10例在原发性肿瘤切除前接受了联合治疗;疾病控制率(DCR)为100%(10/10),客观缓解率(ORR)为70%(7/10)。肝转移灶的ORR为75%(9/12)。1例原发性肿瘤患者和2例肝转移灶患者达到病理完全缓解(pCR)。共有5例患者同时切除了原发性肿瘤和肝转移灶;9例患者接受了肝转移灶微波消融治疗。共有7例患者被评估为无疾病证据(NED),在对原发性和转移性病变进行多模式治疗后,中位无进展生存期(PFS)为9.2(1.5-15.8)个月。未观察到严重的免疫相关不良事件(irAE)和手术并发症。 结论:PD-1阻断联合化疗和贝伐单抗对pMMR/MSS CRLM患者可能是安全有效的。这种治疗策略可能导致更好的肿瘤退缩和更高的NED率。
Zhonghua Wei Chang Wai Ke Za Zhi. 2022-3-25
Cancers (Basel). 2020-10-27