Lancet子刊:中山六院团队报道大肠癌免疫治疗临床研究新进展
创作:aluba 审核:aluba 2021年11月08日
  • 34名局部进展期结直肠癌患者随机分为2组,术前17名接受特瑞普利单抗+塞来昔布治疗,17名接受特瑞普利单抗治疗,术后继续接受特瑞普利单抗+塞来昔布或特瑞普利单抗治疗;
  • 所有患者完成了R0切除,特瑞普利单抗+塞来昔布组及特瑞普利单抗组分别有88%及65%完成了病理学的完全应答(切除的肿瘤样本中无存活肿瘤细胞);
  • 中位随访14.9个月期间,所有患者存活且未复发;
  • 在新辅助治疗期间及辅助治疗期间,均仅有1名患者发生3级以上不良事件。
主编推荐语
aluba
中山大学附属第六医院的邓艳红团队在Lancet Gastroenterology & Hepatology上发表的一项2期临床试验结果,在34名错配修复缺陷/微卫星高度不稳定的局部进展期结直肠癌患者中,特瑞普利单抗单药或联用塞来昔布的新辅助治疗可很好地诱导病理学的完全应答(pathological complete response),且安全性良好。同时,所有患者都完成了R0切除,且在约15个月的中位随访期间,均存活且未复发。
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Neoadjuvant PD-1 blockade with toripalimab, with or without celecoxib, in mismatch repair-deficient or microsatellite instability-high, locally advanced, colorectal cancer (PICC): a single-centre, parallel-group, non-comparative, randomised, phase 2 trial

特瑞普利单抗联用或不联用塞莱昔布用于错配修复缺陷或微卫星高度不稳定的局部进展期结直肠癌患者的新辅助治疗:单中心平行随机2期临床试验

10.1016/S2468-1253(21)00348-4

2021-10-21, Article

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Background: PD-1 blockade is highly effective in patients with mismatch repair-deficient or microsatellite instability-high metastatic colorectal cancer. The role of single-agent PD-1 blockade in the neoadjuvant setting for resectable mismatch repair-deficient or microsatellite instability-high colorectal cancer remains unclear. We investigated the efficacy and safety of PD-1 blockade with toripalimab, with or without the COX-2 inhibitor celecoxib, as neoadjuvant treatment for mismatch repair-deficient or microsatellite instability-high, locally advanced, colorectal cancers.
Methods: The PD-1 Inhibitor in Microsatellite Instability Colorectal Cancer (PICC) trial was a single-centre, open-label, parallel-group, non-comparative, randomised, phase 2 study undertaken at the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China). Eligible patients were aged 18–75 years, had histologically confirmed mismatch repair-deficient or microsatellite instability-high colorectal cancer, had clinical stage T3–T4 or any T with lymph node positivity (N+), Eastern Cooperative Oncology Group performance score of 0 or 1, and adequate haematological, hepatic, and renal function. Participants were randomly assigned (1:1), without any stratification or balanced blocking, to receive toripalimab 3 mg/kg intravenously on day 1, with or without celecoxib 200 mg orally twice daily from day 1 to 14 of each 14-day cycle, for six cycles before surgical resection. Adjuvant treatment with toripalimab with or without celecoxib was permitted at the investigators' discretion. The primary endpoint was the proportion of patients with pathological complete response, defined as tumours without any viable tumour cells in the resected primary tumour sample and all sampled regional lymph nodes. All efficacy and safety analyses were assessed in the modified intention-to-treat population, which included all patients who were randomly assigned to treatment and who received at least one dose of toripalimab. This trial is registered with ClinicalTrials.gov, NCT03926338, and is ongoing.
Findings: Between May 1, 2019, and April 1, 2021, 53 patients were screened, of whom 34 were randomly assigned to either the toripalimab plus celecoxib group (n=17) or the toripalimab monotherapy group (n=17). As of data cutoff (Aug 10, 2021), median follow-up was 14·9 months (IQR 8·8–17·0). All patients received study treatment and underwent surgical resection; there were no treatment-related surgical delays. All 34 patients had an R0 resection (>1 mm resection margin). 15 of 17 patients (88% [95% CI 64–99]) in the toripalimab plus celecoxib group and 11 of 17 patients (65% [38–86]) in the toripalimab monotherapy group had a pathological complete response. All patients continued to receive adjuvant toripalimab with or without celecoxib for a total perioperative duration of 6 months and were alive and free of recurrence at data cutoff. During neoadjuvant treatment, ten (59%) patients in the toripalimab plus celecoxib group and ten (59%) in the toripalimab monotherapy group had grade 1–2 treatment-related adverse events. Only one (3%) of 34 patients, who was in the toripalimab plus celecoxib group, had a grade 3 or higher treatment-related adverse event during the neoadjuvant phase, which was grade 3 increased aspartate aminotransferase levels. In the adjuvant phase, only one (3%) of 34 patients, who was in the toripalimab monotherapy group, had a grade 3 or higher treatment-related adverse events, which was grade 3 increased aspartate aminotransferase and alanine aminotransferase levels.
Interpretation: Neoadjuvant toripalimab with or without celecoxib could be a potential therapeutic option for patients with mismatch repair deficient or microsatellite instability-high, locally advanced, colorectal cancer. This treatment was associated with a high pathological complete response rate and an acceptable safety profile, which did not compromise surgery. Longer term follow-up is needed to assess effects on survival-related endpoints.
Funding: The National Key R&D Program of China, the National Natural Science Foundation of China, and the Chinese Society of Clinical Oncology-Junshi Biosciences Oncology Immunity Research.
Translation: For the Chinese translation of the abstract see Supplementary Materials section.

First Authors:
Huabin Hu,Liang Kang,Jianwei Zhang,Zehua Wu

Correspondence Authors:
Yanhong Deng

All Authors:
Huabin Hu,Liang Kang,Jianwei Zhang,Zehua Wu,Hui Wang,Meijin Huang,Ping Lan,Xiaojian Wu,Chao Wang,Wuteng Cao,Jiancong Hu,Yan Huang,Liang Huang,Huaiming Wang,Lishuo Shi,Yue Cai,Cailu Shen,Jiayu Ling,Xiaoyu Xie,Yonghua Cai,Xiaowen He,Ruoxu Dou,Jiaming Zhou,Tenghui Ma,Xingwei Zhang,Shuangling Luo,Weihao Deng,Li Ling,Hao Liu,Yanhong Deng

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