Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study.
Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study.
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DOI：
10.1016/s1470-2045(17)30104-3
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发表时间：
2017-04
期刊：
影响因子：
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通讯作者：
Eng C
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作者：
Morris VK;Salem ME;Nimeiri H;Iqbal S;Singh P;Ciombor K;Polite B;Deming D;Chan E;Wade JL;Xiao L;Bekaii-Saab T;Vence L;Blando J;Mahvash A;Foo WC;Ohaji C;Pasia M;Bland G;Ohinata A;Rogers J;Mehdizadeh A;Banks K;Lanman R;Wolff RA;Streicher H;Allison J;Sharma P;Eng C
摘要肛管鳞状细胞癌（SCCA）是一种罕见的与人乳头瘤病毒（HPV）感染相关的恶性肿瘤。对于转移性疾病的治疗尚无共识的治疗方法。由于瘤内HPV癌蛋白上调免疫检查点蛋白（如PD-1）以逃避免疫介导的细胞毒性，我们对转移性SCCA患者进行了抗PD-1抗体nivolumab的试验。我们在美国的10个学术中心进行了单臂、多中心、二期试验。我们招募了难治性转移性SCCA患者，他们每2周给予尼武单抗（3mg /kg）。主要终点是根据实体肿瘤反应评价标准（1.1版）在意向治疗人群中的反应。在数据截止时，研究仍在进行中，患者仍在接受治疗。该研究已在ClinicalTrials.gov注册，编号NCT02314169。我们筛选了39例患者，其中37例入组并接受了至少一剂纳武单抗。在37例患者中，9例（24% [95% CI 15-33]）有反应。有2个完整回答和7个部分回答。3级不良事件为贫血（n=2）、疲劳（n=1）、皮疹（n=1）和甲状腺功能减退（n=1）。无严重不良事件报告。据我们所知，这是第一个完成免疫治疗SCCA的二期试验。Nivolumab作为转移性SCCA患者的单药治疗具有良好的耐受性和有效性。免疫检查点阻断似乎是一个有希望的方法，为患者与这种孤儿疾病。国家癌症研究所/癌症治疗评估计划，HPV和肛门癌基金会，eb肛门癌基金，德克萨斯大学MD安德森登月计划，以及一位匿名的慈善捐赠者。
Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for the treatment of metastatic disease. Because intratumoral HPV oncoproteins upregulate immune checkpoint proteins such as PD-1 to evade immune-mediated cytotoxicity, we did a trial of the anti-PD-1 antibody nivolumab for patients with metastatic SCCA. We did this single-arm, multicentre, phase 2 trial at ten academic centres in the USA. We enrolled patients with treatment-refractory metastatic SCCA, who were given nivolumab every 2 weeks (3 mg/kg). The primary endpoint was response according to Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. At the time of data cutoff, the study was ongoing, with patients continuing to receive treatment. The study is registered with ClinicalTrials.gov, number NCT02314169. We screened 39 patients, of whom 37 were enrolled and received at least one dose of nivolumab. Among the 37 patients, nine (24% [95% CI 15–33]) had responses. There were two complete responses and seven partial responses. Grade 3 adverse events were anaemia (n=2), fatigue (n=1), rash (n=1), and hypothyroidism (n=1). No serious adverse events were reported. To our knowledge, this is the first completed phase 2 trial of immunotherapy for SCCA. Nivolumab is well tolerated and effective as a monotherapy for patients with metastatic SCCA. Immune checkpoint blockade appears to be a promising approach for patients with this orphan disease. National Cancer Institute/Cancer Therapy Evaluation Program, the HPV and Anal Cancer Foundation, the E B Anal Cancer Fund, The University of Texas MD Anderson Moon Shots Program, and an anonymous philanthropic donor.