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Larotinib in patients with advanced and previously treated esophageal squamous cell carcinoma with epidermal growth
Rongrui Liu1, Lianke Liu2, Chuanhua Zhao1,3
1Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, No. 8 Dongda Avenue, Fengtai District, Beijing, 100071, China.
Background:
Larotinib is a new first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. This open-label, phase 1b study is aimed to evaluate the efficacy, safety of larotinib in patients with advanced esophageal squamous cell carcinoma (ESCC) with EGFR overexpression or amplification pretreated with one or more system regimens, and to recommend an appropriate dose for its further study.
Methods:
Patients received larotinib orally at 3 doses (250, 300, 350 mg), once daily. Clinical response was evaluated every 8 weeks according to RECIST v1.1 criteria by both investigators and independent radiology review (IRC).
Results:
81 patients were enrolled. The investigator-assessed overall response rate (ORR) was 13.7% (10/73), all responses were observed in the 350 mg group of which ORR up to 20.0% (10/50), with 10 of them having EGFR overexpression and 4 having EGFR amplification. Per IRC assessment, ORR for all patients and 350 mg group were 13.9% (10/72) and 16.3% (8/50). In the 350 mg group, median overall survival (OS) and progression-free survival (PFS) were 8.0 (95% CI 4.9-10.2) months and 3.4 (95% CI 2.4-3.7) months, respectively. The most common treatment-related adverse events (TRAEs) were diarrhea, rash, and palmar-plantar erythrodysesthesia syndrome, elevated AST/ALT, vomiting, similarly with other EGFR TKIs.
Conclusions:
Larotinib demonstrated promising antitumor activity and manageable safety profiles in patients with pre-treated advanced ESCC with EGFR overexpression or amplification, especially at the dose of 350 mg, which showed better efficacy and acceptable safety. A phase 3 study is underway on 350 mg larotinib in ESCC patients with EGFR overexpression.
Trial Registration:
This trial was retrospectively registered on 25/03/2019, NCT03888092. https://clinicaltrials.gov/ct2/show/NCT03888092 .
Insights
Larotinib shows promising antitumor activity in advanced esophageal squamous cell carcinoma (ESCC) patients with EGFR overexpression or amplification. The 350 mg dose demonstrated better efficacy and manageable safety, warranting further study.
Area of Science:
- Oncology
- Pharmacology
Background:
- Larotinib is a novel first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor.
- Esophageal squamous cell carcinoma (ESCC) is a significant global health concern.
- EGFR overexpression or amplification is a key driver in some ESCC cases.
Purpose of the Study:
- To evaluate the efficacy and safety of larotinib in pretreated advanced ESCC patients with EGFR alterations.
- To determine the optimal dose of larotinib for further clinical investigation.
Main Methods:
- An open-label, phase 1b study involving 81 patients with advanced ESCC.
- Patients received oral larotinib at doses of 250, 300, or 350 mg daily.
- Clinical response was assessed using RECIST v1.1 criteria every 8 weeks.
Main Results:
- The overall response rate (ORR) was 13.7% by investigator assessment and 13.9% by independent review.
- The 350 mg dose showed an ORR of 20.0% (investigator) and 16.3% (independent review).
- Median overall survival and progression-free survival in the 350 mg group were 8.0 and 3.4 months, respectively. Common adverse events included diarrhea and rash.
Conclusions:
- Larotinib exhibits promising antitumor activity and a manageable safety profile in pretreated advanced ESCC with EGFR overexpression or amplification.
- The 350 mg dose demonstrated superior efficacy and acceptable safety.
- A Phase 3 study of 350 mg larotinib in ESCC patients with EGFR overexpression is ongoing.
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