背景:尽管采用标准联合化疗治疗,但无法切除的肝内胆管癌(iCCA)的预后较差。我们旨在评估放疗联合抗PD-1抗体在不可切除的iCCA中的疗效和安全性,而没有远处转移。
方法:在本II期研究中,纳入了经组织病理学证实不可切除的原发或术后复发iCCA且无远处转移的患者.患者接受剂量≥45Gy(每分2-2.5Gy)的外部放疗,其次是抗PD-1免疫疗法(卡利珠单抗200毫克一次,每3周)在完成放疗后7天内开始作为一线治疗。主要终点是1年无进展生存率(PFS)。次要终点包括安全性,客观反应率(ORR),疾病控制率(DCR),总生存率(OS)。
结果:从2019年12月至2021年3月,36例患者完成了放疗和至少一个周期的免疫治疗,并纳入疗效和安全性分析。中位随访时间为19.0个月(IQR12.0-24.0),一年PFS率为44.4%(95%CI,30.8-64.0)。中位PFS为12.0个月(95%CI,7.5-不可估计);中位OS为22.0个月(95%CI,15.0-不可估计)。ORR为61.1%,DCR为86.1%。36例患者中有17例(47.2%)经历了任何级别的治疗相关不良反应(AE)。最常见的AE是反应性皮肤毛细血管内皮增生(25.0%)。5例(13.9%)患者出现≥3级治疗相关不良事件,包括淋巴细胞减少(5.6%),大疱性皮炎(2.8%),血小板计数减少(2.8%),深静脉血栓形成(2.8%)。
结论:外部放疗加卡姆瑞珠单抗,作为一线治疗,达到其主要终点,并在不可切除的iCCA无远处转移的患者中显示出抗肿瘤活性和低毒性水平,保证进一步调查。
背景:NCT03898895。2019年4月2日注册。
BACKGROUND: Unresectable intrahepatic cholangiocarcinoma (iCCA) has a poor prognosis despite treatment with standard combination chemotherapy. We aimed to evaluate the efficacy and safety of radiotherapy in combination with an anti-PD-1 antibody in unresectable iCCA without distant metastases.
METHODS: In this phase II study, patients with histopathologically confirmed unresectable primary or postoperative recurrent iCCA without distant metastases were enrolled. Patients received external radiotherapy with a dose of ≥45 Gy (2-2.5 Gy per fraction), followed by anti-PD-1 immunotherapy (camrelizumab 200 mg once, every 3 weeks) initiated within 7 days after completion of radiotherapy as first-line therapy. The primary endpoint was 1-year progression-free survival (PFS) rate. The secondary end points included safety, objective response rate (ORR), disease control rate (DCR), and overall survival (OS).
RESULTS: From December 2019 to March 2021, 36 patients completed radiotherapy and at least one cycle of immunotherapy and were included in efficacy and safety analyses. The median follow-up was 19.0 months (IQR 12.0-24.0), and the one-year PFS rate was 44.4% (95% CI, 30.8-64.0). The median PFS was 12.0 months (95% CI, 7.5-not estimable); the median OS was 22.0 months (95% CI, 15.0-not estimable). The ORR was 61.1% and the DCR was 86.1%. Seventeen of 36 (47.2%) patients experienced treatment-related adverse effects (AEs) of any grade. The most common AE was reactive cutaneous capillary endothelial proliferation (25.0%). Five (13.9%) patients experienced grade ≥3 treatment-related AEs, including decreased lymphocyte (5.6%), bullous dermatitis (2.8%), decreased platelet count (2.8%), and deep-vein thrombosis (2.8%).
CONCLUSIONS: External radiotherapy plus camrelizumab, as first-line therapy, met its primary endpoint and showed antitumor activity and low toxicity levels in patients with unresectable iCCA without distant metastases, warranting further investigation.
BACKGROUND: NCT03898895. Registered 2 April 2019.