Anlotinib Monotherapy for Refractory Metastatic Colorectal Cancer: A Double-Blinded, Placebo-Controlled, Randomized
Yihebali Chi1, Yongqian Shu2, Yi Ba3
1Department 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, People's Republic of China.
Background:
Treatment options for refractory metastatic colorectal cancer (mCRC) were limited. Anlotinib is a novel multitarget tyrosine kinase inhibitor. ALTER0703 study was conducted to assess efficacy and safety of anlotinib for patients with refractory mCRC.
Materials And Methods:
This was a multicenter, double-blinded, placebo-controlled, randomized phase III trial involving 33 hospitals in China. Patients had taken at least two lines of therapies were 2:1 randomized to receive oral anlotinib (12 mg/day; days 1-14; 21 days per cycle) or placebo, plus best supportive care. Randomization was stratified by previous VEGF-targeting treatments and time from diagnosis to metastases. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL), and safety.
Results:
A total of 419 patients (anlotinib: 282; placebo: 137) were treated from December 2014 to August 2016. The median PFS was improved in anlotinib group (4.1 months; 95% confidence interval [CI], 3.4-4.5) over placebo group (1.5 months; 95% CI, 1.4-1.5), with a hazard ratio (HR) of 0.34 (95% CI, 0.27-0.43; p < .0001). However, median OS was similar between two groups (8.6 months; 95% CI, 7.8-9.7 vs. 7.2 months; 95% CI, 6.2-8.8; HR, 1.02; p = .870). Improvements of ORR and DCR were observed in anlotinib over placebo. The most common grade ≥ 3 anlotinib related adverse events were hypertension (20.92%), increased γ-GT (7.09%), and hand-foot skin reaction (6.38%).
Conclusion:
Anlotinib was tolerated in Chinese patients with refractory mCRC. Although OS did not reach significant difference, anlotinib still provided clinical benefits by substantially prolonged PFS in these patients.
Implications For Practice:
In this randomized clinical trial that included 419 patients with refractory metastatic colorectal cancer, substantial prolonged in progression-free survival was noted in patients who received anlotinib compared with those given placebo. Improvements on objective response rate and disease control rate was also observed in anlotinib group. However, overall survival was similar between the two groups. In a word, in third-line or above treatment of Chinese patients with refractory metastatic colorectal cancer, anlotinib provided clinical benefit by significantly prolonged progression-free survival.
Insights
Anlotinib significantly prolonged progression-free survival in patients with refractory metastatic colorectal cancer. While overall survival did not differ, anlotinib demonstrated clinical benefits and was well-tolerated in this population.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Metastatic colorectal cancer (mCRC) presents limited treatment options for refractory cases.
- Anlotinib, a novel multi-target tyrosine kinase inhibitor, offers a potential therapeutic avenue.
Purpose of the Study:
- To assess the efficacy and safety of anlotinib in patients with refractory mCRC.
- To evaluate anlotinib's impact on overall survival, progression-free survival, and response rates.
Main Methods:
- A multicenter, double-blinded, placebo-controlled, randomized phase III trial (ALTER0703) was conducted in China.
- 419 patients with refractory mCRC received either oral anlotinib or placebo, plus best supportive care.
- Primary endpoint: overall survival (OS); Secondary endpoints: progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL), and safety.
Main Results:
- Median PFS significantly improved with anlotinib (4.1 months) versus placebo (1.5 months) (HR=0.34, p < .0001).
- Median OS was similar between anlotinib and placebo groups (8.6 vs. 7.2 months).
- Anlotinib showed improved ORR and DCR, with common adverse events including hypertension and hand-foot skin reaction.
Conclusions:
- Anlotinib demonstrated tolerability in Chinese patients with refractory mCRC.
- Anlotinib provided clinical benefits by substantially prolonging PFS, despite no significant difference in OS.
- The study suggests anlotinib's value in third-line or later treatment for refractory mCRC.
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