Shen Cailu, Hu Huabin, Cai Yue, Ling Jiayu, Zhang Jianwei, Wu Zehua, Xie Xiaoyu, Huang Meijin, Wang Hui, Kang Liang, Lan Ping, Wu Xiaojian, Liu Guangjian, Wan Yunle, Zhou Zhiyang, Huang Yan, Li Fangqian, Wang Huaiming, Ma Tenghui, Luo Shuangling, Cai Yonghua, Shi Lishuo, Deng Yanhong
Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, China.
Ann Transl Med. 2022 Feb;10(4):171. doi: 10.21037/atm-21-6731.
The aim of this non-randomized single-center phase II trial was to prospectively assess the clinical efficacy of triplet chemotherapy with modified 5-fluorouracil, folinic acid, oxaliplatin, and irinotecan (mFOLFOXIRI) plus bevacizumab as conversion therapy for initially unresectable rat sarcoma viral oncogene homolog (RAS)/v-raf murine sarcoma viral oncogene homolog B1 (BRAF)/phosphatidylinositol-3 kinase catalytic alpha (PIK3CA) mutant colorectal liver-limited metastases (CRLMs).
Patients with // mutant initially unresectable CRLMs were recruited at a ratio of 2:1 to receive mFOLFOXIRI plus bevacizumab (experimental group) or mFOLFOXIRI alone (control group). The rate of patients attaining no evidence of disease (NED) was the primary endpoint. The secondary endpoints included objective response rate (ORR), depth of tumor response (DpR), secondary resection rate, progression-free survival (PFS), overall survival (OS), and safety.
The rate of NED achieved was 40.7% and 30.8%, respectively, in the experimental (n=54) and control groups (n=26); the adjusted odds ratio was 4.519 [95% confidence interval (CI): 1.247-16.375, P=0.022]. The ORR was 77.4% in the experimental group and 60.0% in the control group (P=0.112). The median DpR was significantly greater in the experimental group (45.6% 34.9%, P=0.041). The median PFS was 12.6 months in the experimental group and 9.1 months in the control group [adjusted hazard ratio (HR): 0.584, 95% CI: 0.304-1.121, P=0.106]. Median OS was prolonged in the experimental group compared with the control group (42.6 35.3 months, adjusted HR: 0.443, 95% CI: 0.195-1.006, P=0.052). Thirty patients (55.6%) in the experimental group and 16 (61.5%) in the control group experienced grade 3/4 adverse events.
We observed that the combination of mFOLFOXIRI and bevacizumab increased the rate of clinical NED and showed a trend toward improved survival compared with mFOLFOXIRI alone. This could represent a conversion therapy option for fit patients with initially unresectable // mutant CRLMs.
这项非随机单中心II期试验的目的是前瞻性评估改良氟尿嘧啶、亚叶酸钙、奥沙利铂和伊立替康（mFOLFOXIRI）联合贝伐单抗作为初始不可切除的大鼠肉瘤病毒癌基因同源物（RAS）/v-raf鼠肉瘤病毒癌基因同源物B1（BRAF）/磷脂酰肌醇-3激酶催化亚基α（PIK3CA）突变型结直肠肝局限性转移瘤（CRLMs）转化治疗的临床疗效。
按2:1的比例招募初始不可切除的//突变型CRLMs患者，分别接受mFOLFOXIRI联合贝伐单抗（试验组）或单纯mFOLFOXIRI（对照组）治疗。达到无疾病证据（NED）的患者比例为主要终点。次要终点包括客观缓解率（ORR）、肿瘤缓解深度（DpR）、二次切除率、无进展生存期（PFS）、总生存期（OS）和安全性。
试验组（n = 54）和对照组（n = 26）达到NED的比例分别为40.7%和30.8%；调整后的优势比为4.519[95%置信区间（CI）：1.247 - 16.375，P = 0.022]。试验组的ORR为77.4%，对照组为60.0%（P = 0.112）。试验组的中位DpR显著更高（45.6% 34.9%，P = 0.041）。试验组的中位PFS为12.6个月，对照组为9.1个月[调整后的风险比（HR）：0.584，95% CI：0.304 - 1.121，P = 0.106]。试验组的中位OS较对照组延长（42.6 35.3个月，调整后的HR：0.443，95% CI：0.195 - 1.006，P = 0.052）。试验组30例患者（55.6%）和对照组16例患者（61.5%）发生3/4级不良事件。
我们观察到，与单纯mFOLFOXIRI相比，mFOLFOXIRI联合贝伐单抗可提高临床NED率，并显示出改善生存的趋势。这可能是适合初始不可切除的//突变型CRLMs患者的一种转化治疗选择。
