Avelumab 联合axitinib治疗不可切除或转移性 B3 型胸腺瘤和胸腺癌：一项单臂、多中心、2 期试验

SCI

23 September 2022

Avelumab plus axitinib in unresectable or metastatic type B3 thymomas and thymic carcinomas (CAVEATT): a single-arm, multicentre, phase 2 trial

(IF: Lancet Oncol., 54.433)

Conforti F, Zucali PA, Pala L, Catania C, Bagnardi V, Sala I, Della Vigna P, Perrino M, Zagami P, Corti C, Stucchi S, Barberis M, Guerini-Rocco E, Di Venosa B, De Vincenzo F, Cordua N, Santoro A, Giaccone G, Martino De Pas T. Avelumab plus axitinib in unresectable or metastatic type B3 thymomas and thymic carcinomas (CAVEATT): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2022 Sep 9:S1470-2045(22)00542-3. 

Correspondence: Dr Fabio Conforti, Division of Melanoma, Sarcoma, and Rare Tumors, European Institute of Oncology, IRCCS, 20141 Milan, Italy fabio.conforti@gavazzeni.it; @fabioconforti1 

Methods 方法

CAVEATT was a single-arm, multicentre, phase 2 trial, conducted in two Italian centres (the European Instituteof Oncology and the Humanitas Institute, Milan) in patients with histologically confirmed type B3 thymoma or thymic carcinoma, with advanced stage of disease who had progressed after at least one line of platinum-based chemotherapy. Previous treatment with an anti-angiogenesis drug was allowed but not with immune checkpoint inhibitors. Other inclusion criteria were age 18 years or older, an Eastern Cooperative Oncology Group performance status of 0–2, progressive disease, and presence of measurable disease according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. Patients received avelumab 10 mg/kg intravenously every 2 weeks and axitinib 5 mg orally twice daily until disease progression or unacceptable toxicity. The primary endpoint was the centrally assessed overall response rate according to RECIST version 1.1. Patients who received at least one cycle of treatment and had at least one CT scan after treatment start at scheduled time point by protocol were judged assessable for response and were included in efficacy and safety analyses. This study is registered with EUDRACT, 2017–004048–38; enrolment is completed and follow-up is ongoing.

CAVEATT是一项单臂、多中心、2期试验，在两个意大利中心（欧洲肿瘤研究所和米兰人道主义研究所）纳入了组织学确诊的B3型胸腺瘤或胸腺癌患者，这些患者在经历至少一种铂类化疗后病情进展。允许使用抗血管生成药物进行先前的治疗，但不允许使用免疫检查点抑制剂。其他纳入标准包括年龄18岁或以上、东部肿瘤协作组体能状态为0-2、疾病进展，以及根据实体肿瘤反应评估标准（RECIST）1.1版存在可测量的疾病。患者每2周静脉接受avelumab 10mg/kg，每日两次口服axitinib 5mg，直至病情进展或出现不可耐受的毒性。主要终点是根据RECIST 1.1版集中评估的总体缓解率。根据方案接受了至少一个治疗周期且在预定时间点开始治疗后至少进行了一次CT扫描的患者被判定为可评估相应，纳入疗效和安全性分析。本研究在EUDRACT注册，2017–004048–38；注册已完成，后续工作正在进行中。

Findings 发现

Between April 22, 2019, and June 30, 2021, 32 patients were enrolled. 27 patients had a thymic carcinoma, three a type B3 thymoma, and two a mixed type B3 thymoma and thymic carcinoma. 29 (91%) of 32 patients had stage IVB disease and 13 (41%) of 32 had been pretreated with an anti-angiogenesis drug. 11 of 32 patients had an overall response; thus the overall response rate was 34% (90% CI 21–50); no patients had a complete response, 11 (34%) had a partial response, 18 (56%) had stable disease, and in two patients (6%) progressive disease was the best response. The most common grade 3 or 4 adverse event was hypertension (grade 3 in six [19%] of 32 patients). Four (12%) of 32 patients developed serious adverse events that were new-onset immune-related adverse events, including one grade 3 interstitial pneumonitis, one grade 4 polymyositis, and two grade 3 polymyositis. There were no treatmentrelated deaths.

2019年4月22日至2021年6月30日期间，共有32例患者入组。27例患者患有胸腺癌，3例患者患有B3型胸腺瘤，2例患者患有混合型B3胸腺瘤和胸腺癌。32例患者中有29例 (91%) 患有IVB期疾病，32例患者中有13例 (41%) 曾接受过抗血管生成药物治疗。32 例患者中有11例有总体响应；因此总体缓解率为 34% (90% CI 21–50)；没有患者完全缓解，11例（34%）部分缓解，18例（56%）疾病稳定，2例（6%）病情进展为最佳缓解。最常见的3级或4级不良事件是高血压（32例患者中有6例为3级，占19%）。32例患者中有4例（12%）发生了新发免疫相关的严重不良事件，包括1例3级间质性肺炎、1例4级多发性肌炎和2例3级多发性肌炎。没有与治疗相关的死亡。

Interpretation 解释

Avelumab combined with axitinib has promising anti-tumour activity and acceptable toxicity in patients with advanced type B3 thymoma and thymic carcinoma progressing after chemotherapy, and could emerge as a new standard treatment option in this setting.

Avelumab联合axitinib对晚期 B3 型胸腺瘤和化疗后进展的胸腺癌患者具有良好的抗肿瘤活性和可接受的毒性，并可能成为这种情况下的新标准治疗选择。