Combination of anlotinib and irinotecan in the second-line treatment of metastatic colorectal cancer: a multicenter phase 1/2 trial.
10.3760/cma.j.cn112152-20210722-00535
- Author:
Bo ZHANG
1
;
Xi WANG
2
;
Ling Jun ZHU
3
;
Wei You ZHU
3
;
Qun LI
1
;
Yun LIU
1
;
Ling QI
1
;
Yong Qian SHU
3
;
Jing HUANG
1
Author Information
1. Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
2. Daycare Center, Peking University Cancer Hospital & Institute, Beijing 100142, China.
3. Department of Medical Oncology, Jiangsu Province Hospital, Nanjing 210029, China.
- Publication Type:Journal Article
- Keywords:
Anlotinib;
Colorectal neoplasms;
Efficacy;
Irinotecan;
Safety
- MeSH:
Humans;
Antineoplastic Combined Chemotherapy Protocols/adverse effects*;
Colorectal Neoplasms/pathology*;
Indoles/therapeutic use*;
Irinotecan/therapeutic use*;
Prospective Studies
- From:
Chinese Journal of Oncology
2023;45(1):95-100
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To evaluate the safety and efficacy of anlotinib plus irinotecan in the second-line treatment of patients with metastatic colorectal cancer (mCRC). Methods: This prospective phase 1/2 study was conducted in 2 centers in China (Cancer Hospital of Chinese Academy of Medical Sciences and Jiangsu Province Hospital). We enrolled patients with mCRC whose disease had progressed after first-line systemic therapy and had not previously treated with irinotecan to receive anlotinib plus irinotecan. In the phase 1 of the trial, patients received anlotinib (8 mg, 10 mg or 12 mg, po, 2 weeks on/1 week off) in combination with fixed-dose irinotecan (180 mg/m(2), iv, q2w) to define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). In the phase 2, patients were treated with the RP2D of anlotinib and irinotecan. The primary endpoints were MTD and objective response rate (ORR). Results: From May 2018 to January 2020, a total of 31 patients with mCRC were enrolled. Anlotinib was well tolerated in combination with irinotecan with no MTD identified in the phase 1, and the RP2D was 12 mg. Thirty patients were evaluable for efficacy analysis. Eight patients achieved partial response, and 21 had stable disease, 1 had progressive disease. The ORR was 25.8% and the disease control rate was 93.5%. With a median follow-up duration of 29.5 months, the median progression-free survival and overall survival were 6.9 months (95% CI: 3.7, 9.3) and 17.6 months (95% CI: 12.4, not evaluated), respectively. The most common grade 3 treatment-related adverse events (≥10%) were neutropenia (25.8%) and diarrhea (16.1%). There was no treatment-related death. Conclusion: The combination of anlotinib and irinotecan has promising anti-tumor activity in the second-line treatment of mCRC with a manageable safety profile.
