背景:现有证据表明,放射治疗和抗血管生成药物具有协同抗肿瘤作用,可能是实体瘤患者的有希望的治疗选择。因此,我们进行了一项II期试验,以评估全脑放疗(WBRT)联合安洛替尼治疗无靶向驱动突变的非小细胞肺癌(NSCLC)多发脑转移(BMs)的疗效和安全性.
方法:纳入具有来自NSCLC的多个BMs(3)且无靶向驱动突变且对至少一线化疗无效的患者。符合条件的患者接受WBRT(30Gy/10f,5f/周)和安洛替尼(12mg/天,每个周期21天的第1-14天,2个周期)直至疾病进展或治疗不耐受。主要终点是颅内客观缓解率(iORR),次要终点包括颅内无进展生存期(iPFS),疾病控制率(DCR),总生存期(OS),和安全。
结果:在2019年4月至2021年3月期间,21名患者被纳入试验,其中12人年龄60岁(57.1%),13人是男性(61.9%),7人的东部肿瘤协作组表现状况得分为0至1(81.0%),18例腺癌(85.7%),11个有6个BMS(52.4%)。在21名可评估的患者中,iORR为66.7%(1个完全应答+13个部分应答[PR]),28.6%(7PR)有脑外病变。脑内和脑外病变的DCRs分别为90.5%和81.0%,分别。iPFS和OS分别为10.3个月(95%置信区间[CI]:0-24.8个月)和13.4个月(95%CI:0-27.9个月),分别。最常见的毒性是食欲不振(61.9%),高血压(52.4%),疲劳(47.6%),腹泻(28.6%),呕吐(19.0%),头晕(42.9%),头痛(33.3%)。没有患者出现4级或更高级别不良反应。
结论:安洛替尼联合WBRT对无靶向驱动突变的非小细胞肺癌多BM(3)患者有效且耐受性良好。因此,需要进一步的验证研究。临床试验登记号:ChiCTR1900027769。
BACKGROUND: Existing evidence demonstrates that radiotherapy and antiangiogenic drugs have synergistic antitumour effects and may be a promising treatment option for patients with solid tumour. Thus, we performed a phase II
trial to evaluate the efficacy and safety of whole-brain radiotherapy (WBRT) combined with anlotinib for multiple brain metastases (BMs) from non-small cell lung cancer (NSCLC) without targetable driver mutations.
METHODS: Patients with multiple BMs (⩾3) from NSCLC without targetable driver mutations who failed to respond to at least first-line chemotherapy were enrolled. Eligible patients received WBRT (30 Gy/10 f, 5 f/week) and anlotinib (12 mg/day, day 1-14 of 21 days per cycle, 2 cycles) until disease progression or treatment intolerance. The primary endpoint was intracranial objective response rate (iORR) and secondary endpoints included intracranial progression-free survival (iPFS), disease control rate (DCR), overall survival (OS), and safety.
RESULTS: Between April 2019 and March 2021, 21 patients were enrolled in the
trial, of which 12 were aged ⩾60 years (57.1%), 13 were men (61.9%), 7 had an Eastern Cooperative Oncology Group Performance Status score of 0 to 1 (81.0%), 18 had adenocarcinoma (85.7%), and 11 had ⩾6 BMs (52.4%). Of the 21 evaluable patients, the iORR was 66.7% (1 complete response + 13 partial response [PR]), and 28.6% (7PR) had extracerebral lesions. The DCRs for intracerebral and extracerebral lesions were 90.5% and 81.0%, respectively. The iPFS and OS were 10.3 months (95% confidence interval [CI]: 0-24.8 months) and 13.4 months (95% CI: 0-27.9 months), respectively. The most frequently observed toxicities were loss of appetite (61.9%), hypertension (52.4%), fatigue (47.6%), diarrhoea (28.6%), vomiting (19.0%), dizziness (42.9%), and headache (33.3%). None of the patients developed grade 4 or higher grade adverse reactions.
CONCLUSIONS: Anlotinib combined with WBRT is effective and well tolerated in patients with multiple BMs (⩾3) from NSCLC without targetable driver mutations. Therefore, further validation studies are required.Clinical
trial registration number: ChiCTR 1900027769.