Abstract
BackgroundLarotinib 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.MethodsPatients 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).Results81 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.ConclusionsLarotinib 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 registrationThis trial was retrospectively registered on 25/03/2019, NCT03888092. https://clinicaltrials.gov/ct2/show/NCT03888092.
Highlights
Larotinib is a new first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor
Esophageal cancers are histologically classified as squamous cell carcinoma (SCC) and adenocarcinoma [2]
Platinum-based combination chemotherapy remains the standard first-line treatment for unresectable locally advanced, recurrent, or metastatic esophageal cancer. Agents such as irinotecan [5,6,7], docetaxel [8, 9], and paclitaxel [10, 11] have shown single-agent activity, there was no standard treatment for patients who failed first-line therapy, until the approval of PD-1 inhibitors, such as pembrolizumab, nivolumab, and camrelizumab in recently years
Summary
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. Platinum-based combination chemotherapy remains the standard first-line treatment for unresectable locally advanced, recurrent, or metastatic esophageal cancer Agents such as irinotecan [5,6,7], docetaxel [8, 9], and paclitaxel [10, 11] have shown single-agent activity, there was no standard treatment for patients who failed first-line therapy, until the approval of PD-1 inhibitors, such as pembrolizumab, nivolumab, and camrelizumab in recently years. New treatment options are still urgently needed for this patient population
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