Division of Melanoma, Sarcomas, and Rare Tumors, European Institute of Oncology, IRCCS, Milan, Italy; Department of Medical Oncology, Cliniche Humanitas Gavazzeni, Bergamo, Italy.
Department of Biomedical Sciences, Humanitas University, Milan, Italy; Department of Oncology, IRCCS Humanitas Research Hospital, Milan, Italy.
Lancet Oncol. 2022 Oct;23(10):1287-1296. doi: 10.1016/S1470-2045(22)00542-3. Epub 2022 Sep 9.
Patients with advanced type B3 thymoma and thymic carcinoma resistant to chemotherapy have few treatment options. We report the efficacy and safety results of the combination of the anti-PD-L1 inhibitor avelumab with the anti-angiogenesis drug axitinib in patients with advanced type B3 thymoma and thymic carcinoma.
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.
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 treatment-related deaths.
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.
Pfizer.
化疗耐药的晚期 B3 型胸腺瘤和胸腺癌患者治疗选择有限。我们报告了抗 PD-L1 抑制剂avelumab 联合抗血管生成药物阿昔替尼治疗晚期 B3 型胸腺瘤和胸腺癌患者的疗效和安全性结果。
CAVEATT 是一项在意大利两个中心（欧洲肿瘤研究所和米兰的 Humanitas 研究所）进行的单臂、多中心、二期临床试验，纳入了组织学证实的 B3 型胸腺瘤或胸腺癌、疾病进展期、至少接受过一线铂类化疗后进展的患者。允许之前接受过抗血管生成药物治疗，但不允许接受免疫检查点抑制剂治疗。其他纳入标准为年龄≥18 岁、东部肿瘤协作组体力状态 0-2 分、疾病进展、根据实体瘤反应评估标准 1.1（RECIST）版存在可测量的疾病。患者接受avelumab 10mg/kg 静脉注射，每 2 周一次，阿昔替尼 5mg 口服，每日两次，直至疾病进展或出现不可接受的毒性。主要终点是根据 RECIST 版 1.1 评估的中心评估的总缓解率。至少接受过一个周期的治疗并在预定时间点按照方案进行了至少一次治疗后 CT 扫描的患者被判定为可评估缓解，并纳入疗效和安全性分析。该研究在 EUDRACT 注册，编号为 2017-004048-38；招募已完成，随访正在进行中。
2019 年 4 月 22 日至 2021 年 6 月 30 日期间，共纳入 32 例患者。27 例患者为胸腺癌，3 例为 B3 型胸腺瘤，2 例为 B3 型胸腺瘤和胸腺癌混合。32 例患者中 29 例（91%）为 IVB 期疾病，13 例（41%）患者曾接受过抗血管生成药物治疗。32 例患者中有 11 例有总体缓解；因此，总缓解率为 34%（90%CI 21-50）；无完全缓解，11 例（34%）部分缓解，18 例（56%）疾病稳定，2 例（6%）疾病进展为最佳缓解。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[19%]为 3 级）。4 例（12%）患者发生新出现的免疫相关不良事件导致的严重不良事件，包括 1 例 3 级间质性肺炎、1 例 4 级多肌炎和 2 例 3 级多肌炎。无治疗相关死亡。
avelumab 联合阿昔替尼在化疗后进展的晚期 B3 型胸腺瘤和胸腺癌患者中具有有前景的抗肿瘤活性和可接受的毒性，可能成为该治疗领域的一种新的标准治疗选择。
辉瑞。
