Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Haematology (DIPO), University of Milan, Milan, Italy.
Department of Oncology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy.
Eur J Cancer. 2022 Oct;174:31-36. doi: 10.1016/j.ejca.2022.07.009. Epub 2022 Aug 12.
Thymic epithelial tumors (TETs) are rare diseases, with diverse clinical behaviour and prognosis. Intermittent dosing sunitinib represents the gold-standard systemic treatment following platinum-based chemotherapy. To ensure more homogeneous drug exposure, continuous daily dosing (CDD) sunitinib is utilised in other malignancies; however, no data exist in patients with TETs.
We retrospectively examined data from patients with platinum-resistant TETs receiving CDD sunitinib 37.5 mg between 1 May 2017 and 31 May 2022 within the Italian collaborative group for ThYmic MalignanciEs. Primary end-points were median progression-free survival, overall response rate (ORR), median duration of response and major treatment-related adverse events.
A total of 20 consecutive patients (12 thymic carcinoma [TC], 6 B3, and 2 B2 thymoma) were evaluated. Among the 19 patients evaluable for response, ORR was 31.6% (95% CI, 12.5%-56.5%). Among patients with TC, one complete response, four partial responses, and four stable diseases were observed (ORR 41%).The overall median progression-free survival was 7.3 months (95% CI, 4.5-10.3): 7.3 months (95% CI, 4.4-NA) within patients with thymoma and 6.8 months (95% CI, 2.8-10.3) in patients with TC; median duration of response was 10.3 months (95% CI, 2.8-NA). CDD was associated with a manageable toxicity profile. Six patients (30%) experienced >G2 toxicity, nine required dose reduction and three discontinued treatment due to adverse events.
CDD sunitinib showed a relevant antitumor activity and confirmed a good toxicity profile. Similar effectiveness and a better toxicity profile as compared with intermittent dosing historical data suggest that this schedule should be considered.
胸腺瘤(TET)是一种罕见疾病,具有不同的临床行为和预后。顺铂为基础的化疗后,间歇性给药舒尼替尼是金标准的系统治疗。为了确保更均匀的药物暴露,在其他恶性肿瘤中使用连续每日剂量(CDD)舒尼替尼;然而,在 TET 患者中尚无数据。
我们回顾性分析了 2017 年 5 月 1 日至 2022 年 5 月 31 日期间,意大利胸腺瘤恶性肿瘤协作组内接受 CDD 舒尼替尼 37.5mg 的铂耐药 TET 患者的数据。主要终点是中位无进展生存期、总缓解率(ORR)、中位缓解持续时间和主要治疗相关不良事件。
共评估了 20 例连续患者(12 例胸腺癌[TC]、6 例 B3 和 2 例 B2 胸腺瘤)。在 19 例可评估反应的患者中,ORR 为 31.6%(95%CI,12.5%-56.5%)。在 TC 患者中,观察到 1 例完全缓解、4 例部分缓解和 4 例稳定疾病(ORR 41%)。总中位无进展生存期为 7.3 个月(95%CI,4.5-10.3):胸腺瘤患者为 7.3 个月(95%CI,4.4-NA),TC 患者为 6.8 个月(95%CI,2.8-10.3);中位缓解持续时间为 10.3 个月(95%CI,2.8-NA)。CDD 与可管理的毒性特征相关。6 名患者(30%)出现>G2 毒性,9 名患者需要减少剂量,3 名患者因不良事件停止治疗。
CDD 舒尼替尼显示出显著的抗肿瘤活性,并证实了良好的毒性特征。与间歇性给药的历史数据相比,其有效性相当,毒性特征更好,因此应考虑这种方案。