Safety and efficacy of anti-EGFR monoclonal antibody (SCT200) as second-line therapy in advanced esophageal squamous cell carcinoma

Abstract

Objective: The mainstay treatment of esophageal squamous cell carcinoma (ESCC) involves chemotherapy and immunotherapy.However, alternative therapies are required for patients who are refractory or intolerant to existing therapies. Methods: In this single-arm, multicenter, open-label phase Ib study, 30 patients received an intravenous infusion of SCT200, an antiepidermalgrowth factor receptor (EGFR) monoclonal antibody, 6.0 mg/kg once a week for 6 weeks, followed by 8.0 mg/kg once every2 weeks until disease progression or intolerable toxicity. The primary endpoint was the objective response rate (ORR). The secondaryendpoints were progression-free survival (PFS), overall survival (OS), and safety. Results: Thirty patients were enrolled between July 2018 and May 2019. The ORR was 16.7% (95% CI: 5.6%–34.7%). The medianPFS and OS were 3.1 months (95% CI: 1.5–4.3) and 6.8 months (95% CI: 4.7–10.1), respectively. A numerical difference without anystatistical significance in ORR was observed in patients with different EGFR expressions (= 50%: 25.0% vs. < 50%: 0%, P = 0.140)or TP53 mutation abundance (< 10%: 23.8% vs. = 10%: 0%, P = 0.286). Improved median PFS (3.4 vs. 1.4 months, P = 0.006) andOS (8.0 vs. 4.2 months, P = 0.027) were associated with TP53 mutation abundance of < 10%. The most common treatment-relatedadverse events of grade 3 or 4 (occurring in = 2 patients) were hypomagnesemia [7 (23.3%)] and rash [2 (6.7%)]. No treatmentrelateddeath occurred. Conclusions: SCT200 monotherapy as the second- or further-line treatment for advanced ESCC showed favorable efficacy, with anacceptable safety profile. TP53 mutation abundance might serve as a potential predictive biomarker.

Clinical efficacy and identification of factors confer resistance to afatinib (tyrosine kinase inhibitor) in EGFR-overexpressing esophageal squamous cell carcinoma

“… 19 , 24 Several previous trials have tried to target EGFR in unselected patient populations and found low response rates. 18 , 19 , 21 , 25 Therefore, the objective response rate and the median PFS recorded in the present study are promising compared with those in other trials involving unselected advanced ESCC patients. However, more than 60% of the metastatic ESCC patients with EGFR overexpression were still nonresponsive, suggesting that there are other underlying mechanisms in addition to EGFR itself.…”

Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis

“…It is clear that 3D organoid models are an ideal platform for examining host-pathogen interactions in the co-culture of the microbiome and esophageal tissue. In addition, the escalating adoption of target therapies in EC has led to accumulating evidence suggesting the potential involvement of esophageal microbiota in modulating the patient response to these treatments 72,73 , thus presenting a significant focus of research in this field.…”