Abstract
PurposeLarotinib 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 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.ConclusionLarotinib 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 registrationNCT03888092, registered on March 25, 2019, retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT03888092
Programmed death-ligand 1 is prognostic factor in esophageal squamous cell carcinoma and is associated with epidermal growth factor receptor