Kong Tiandong, Chen Lu, Zhao Xiaoli, Duan Fangfang, Zhou Hanli, Wang Lei, Liu Danna
Department of Medical Oncology, Cancer Hospital of Henan University& the Third People's Hospital of Zhengzhou, Henan, China.
Department of Respiratory Medicine, the First Affiliated Hospital of Zhengzhou University, Henan, China.
Invest New Drugs. 2022 Oct;40(5):1095-1105. doi: 10.1007/s10637-022-01279-7. Epub 2022 Jul 5.
Patients with extensive-stage small-cell lung cancer (ES-SCLC) have high relapse rates and poor prognosis. Anlotinib monotherapy has shown promising efficacy for patients with ES-SCLC and has a non-overlapping toxicity profile with chemotherapy. Therefore, the study aims to assess the efficacy and safety of the addition of anlotinib to platinum-chemotherapy as first-line therapy for patients with ES-SCLC. ES-SCLC patients without systemic chemotherapy and immunotherapy were recruited. Eligible patients received anlotinib (12 mg/day, on day 1-14) of a 21-day cycle, with concomitant etoposide (100 mg/m, on day 1-3) plus cisplatin (75 mg/m, on day 1) or carboplatin (AUC = 4-5, on day 1) for 4-6 cycles, followed by indefinite anlotinib maintenance therapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS). Between Jan 15, 2019 and Dec 31, 2020, 25 patients were enrolled. At the data cut-off time (November 3, 2021), the median follow-up was 14.3 months. Median PFS was 10.3 months (95% CI: 6.0-14.5) and median OS was 17.1 months (95% CI: 11.1-19.3). The ORR and DCR were 90% and 100%, respectively. The most common grade 3 or worse treatment-related adverse events were neutropenia (50%), leukopenia (35%), thrombocytopenia (25%), fatigue (10%), nausea (10%), hyponatremia (10%), anemia (10%). One patient discontinued treatment due to treatment-related adverse events. No treatment-related death occurred. Anlotinib plus platinum-chemotherapy as first-line therapy for ES-SCLC has anti-tumor activity, and showed acceptable tolerability. These results provide a basis for future randomized controlled trials.
广泛期小细胞肺癌（ES-SCLC）患者的复发率高且预后较差。安罗替尼单药治疗已显示出对ES-SCLC患者有良好疗效，且与化疗的毒性谱不重叠。因此，本研究旨在评估在铂类化疗基础上加用安罗替尼作为ES-SCLC患者一线治疗的疗效和安全性。招募未接受过全身化疗和免疫治疗的ES-SCLC患者。符合条件的患者接受安罗替尼（12毫克/天，第1 - 14天），每21天为一个周期，同时联合依托泊苷（100毫克/平方米，第1 - 3天）加顺铂（75毫克/平方米，第1天）或卡铂（AUC = 4 - 5，第1天）进行4 - 6个周期的治疗，随后进行不限期的安罗替尼维持治疗。主要终点是无进展生存期（PFS）。次要终点包括客观缓解率（ORR）、疾病控制率（DCR）、总生存期（OS）。在2019年1月15日至2020年12月31日期间，共纳入25例患者。在数据截止时间（2021年11月3日），中位随访时间为14.3个月。中位PFS为10.3个月（95%置信区间：6.0 - 14.5），中位OS为17.1个月（95%置信区间：11.1 - 19.3）。ORR和DCR分别为90%和100%。最常见的3级或更严重的治疗相关不良事件为中性粒细胞减少（50%）、白细胞减少（35%）、血小板减少（25%）、疲劳（10%）、恶心（10%）、低钠血症（10%）、贫血（10%）。1例患者因治疗相关不良事件停药。未发生治疗相关死亡。安罗替尼联合铂类化疗作为ES-SCLC的一线治疗具有抗肿瘤活性，且耐受性可接受。这些结果为未来的随机对照试验提供了依据。
