Division of Hematology/Oncology, Department of Internal Medicine, Naef K. Basile Cancer Institute - NKBCI, American University of Beirut Medical Center, Beirut, Lebanon.
Department of Radiation Oncology, American University of Beirut Medical Center, Beirut, Lebanon.
Radiat Oncol. 2020 Oct 7;15(1):233. doi: 10.1186/s13014-020-01673-6.
Neoadjuvant chemotherapy and short-course radiotherapy followed by resection has been gaining recognition in the treatment of rectal cancer. Avelumab is a fully human immunoglobulin that binds Programmed Death-Ligand 1 (PD-L1) and prevents the suppression of the cytotoxic T cell immune response. This phase II trial evaluates the safety and pathologic response rate of short-course radiation followed by 6 cycles of mFOLFOX6 with avelumab in patients with locally advanced rectal cancer (LARC).
This study is prospective single-arm, multicenter phase II trial adopting Simon's two-stage. Short-course radiation is given over 5 fractions to a total dose of 25 Gy. mFOLFOX6 plus avelumab (10 mg/kg) are given every 2 weeks for 6 cycles. Total mesorectal excision is performed 3-4 weeks after the last cycle of avelumab. Follow up after surgery is done every 3 months to a total of 36 months. Adverse event data collection is recorded at every visit.
13 out of 44 patients with LARC were enrolled in the first stage of the study (30% from total sample size). All patients met the inclusion criteria and received the full short-course radiation course followed by 6 cycles of mFOLFOX6 plus avelumab. 12 out of the 13 patients completed TME while one patient had progression of disease and was dropped out of the study. The sample consisted of 9 (69%) males and 4 (31%) females with median age of 62 (33-73) years. The first interim analysis revealed that 3 (25%) patients achieved pathologic complete response (pCR) (tumor regression grade, TRG 0) out of 12. While 3 (25%) patients had near pCR with TRG 1. In total, 6 out of 12 patients (50%) had a major pathologic response. All patients were found to be MMR proficient. The protocol regimen was well tolerated with no serious adverse events of grade 4 reported.
In patients with LARC, neoadjuvant radiation followed by mFOLFOX6 with avelumab is safe with a promising pathologic response rate. Trial Registration Number and Date of Registration ClinicalTrials.gov NCT03503630, April 20, 2018. https://clinicaltrials.gov/ct2/show/NCT03503630?term=NCT03503630&draw=2&rank=1 .
新辅助化疗和短程放疗后切除在直肠癌治疗中得到越来越多的认可。avelumab 是一种全人源免疫球蛋白，可与程序性死亡配体 1（PD-L1）结合，防止细胞毒性 T 细胞免疫反应受到抑制。这项 II 期试验评估了局部晚期直肠癌（LARC）患者接受短程放疗后 6 个周期 mFOLFOX6 联合avelumab 的安全性和病理缓解率。
本研究是一项前瞻性、单臂、多中心 II 期试验，采用 Simon 的两阶段设计。短程放疗共 5 个疗程，总剂量为 25Gy。mFOLFOX6 加avelumab（10mg/kg）每 2 周给药 1 次，共 6 个周期。avelumab 治疗的最后 1 个周期后 3-4 周行全直肠系膜切除术。术后随访每 3 个月 1 次，共 36 个月。每次就诊时均记录不良事件数据。
44 例 LARC 患者中有 13 例（占总样本量的 30%）进入研究的第 1 阶段。所有患者均符合纳入标准，并接受了完整的短程放疗，随后接受了 6 个周期的 mFOLFOX6 联合 avelumab 治疗。13 例患者中有 12 例完成了 TME，1 例患者因疾病进展而退出研究。该样本由 9 例（69%）男性和 4 例（31%）女性组成，中位年龄为 62（33-73）岁。首次中期分析显示，12 例患者中有 3 例（25%）达到病理完全缓解（肿瘤消退分级，TRG0）。3 例（25%）患者接近病理完全缓解，TRG1。总共有 6 例（50%）患者有主要的病理缓解。所有患者均发现错配修复功能正常。该方案方案耐受良好，无 4 级严重不良事件报告。
在 LARC 患者中，新辅助放疗后接受 mFOLFOX6 联合 avelumab 治疗是安全的，具有较高的病理缓解率。试验注册编号和注册日期 ClinicalTrials.gov NCT03503630，2018 年 4 月 20 日。https://clinicaltrials.gov/ct2/show/NCT03503630?term=NCT03503630&draw=2&rank=1。
