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.
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.
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.
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.
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.
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。
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。
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。
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。
