Nimotuzumab plus concurrent chemo-radiotherapy versus chemo-radiotherapy in unresectable locally advanced esophageal squamous cell carcinoma (ESCC): Interim analysis from a prospective, randomized-controlled, double-blinded, multicenter, and phase III clinical trial (NXCEL1311 Study).

Abstract

4016 Background: 70% of esophageal carcinoma are unresectable at diagnosis. Despite active clinical research on the treatment of esophageal squamous cell carcinoma (ESCC), the long-term survival rate of advanced patients is still very low, with a 5-year survival rate of 30%-40%. A prospective, randomized-controlled, double-blinded, multicenter, and phase III study (NXCEL1311) was designed to investigate the efficacy and safety of nimotuzumab (anti-EGFR humanized monoclonal antibody;abbreviate,Nimo) plus concurrent chemo-radiotherapy compared with placebo plus chemo-radiotherapy in unresectable locally advanced ESCC. Methods: Unresectable locally advanced ESCC patients were randomized (1:1) to receive Nimo (400 mg, qw) or placebo in combination with concurrent chemo-radiotherapy (paclitaxel+ cisplatin+3DCRT/IMRT) for seven weeks. Patients were followed for five years.The primary endpoints were OS, and the secondary endpoints included ORR, DCR, PFS. Results: 200 patients were assigned to the Nimo group (n = 99) or placebo group (n = 101). An interim analysis was conducted for short term efficacy, i.e secondary endpoints (ORR, DCR) and safety, after completing the 6 months follow-up. The OS events are not enough for analysis. The two groups were comparable on baseline characteristics. Eighty patients in the Nimo group and eighty-two patients in the placebo group were evaluable. The ORR of the Nimo group (75/80, 93.8%) was significantly higher than the placebo group (59/82, 72.0%;Chi-square test, p < 0.001). Twenty-six patients in the Nimo group reached the complete response (CR), and ten placebo group patients were CR. The CR rate in the Nimo group was significantly higher than placebo group (32.5% vs.12.2%, p = 0.002). The DCR of the Nimo group and placebo group were 98.8% (79/80) and 91.5% (75/82), respectively (p = 0.064). Single factor logistic aggression analysis showed that age, sex, target lesion number, and BMI did not affect ORR, CR, and DCR (p > 0.05). Multiple factor correction analysis showed the difference of CR, ORR and DCR between two groups is 20% (95%CI 6.0%̃40.2%), 30% (95%CI 10.6%̃52.1%) and 10% (95%CI -5.2%̃31.1%). The incidence of grade 3-5 drug-related AEs was 11.1%vs.10.9% (p > 0.05). Common drug-related AEs in patients with Nimo plus chemo-radiotherapy treatment were leucopenia, neutrophilic granulocytopenia, thrombocytopenia, hemoglobin, bone marrow inhibition, nutritional anemia, and radioactive inflammation. Conclusions: This interim analysis showed that nimotuzumab in combination with chemo-radiotherapy is safe and can increase the CRR and ORR of the treated patients. The OS needs to be followed and finally analyzed. Clinical trial information: 02409186.

Advancements in the research of immune checkpoint inhibitors for the treatment of advanced esophageal squamous cell carcinoma

“…A mid-term analysis of shortterm efficacy and safety was conducted after 6 months of follow-up. The results showed that the objective response rate (ORR) in the nimotuzumab group was significantly higher than in the placebo group (93.8% vs. 72.0%); the complete response rate (CR) was also significantly higher in the nimotuzumab group (32.5% vs. 12.2%) [78]. Based on the mid-term results, it can be concluded that nimotuzumab combined with chemoradiotherapy is safe and can improve the complete response rate (CRR) and ORR in treated patients.…”

Potent molecular-targeted therapies for advanced esophageal squamous cell carcinoma

“…297,298 A phase III NXCEL1311 trial was conducted to compare the treatment efficacy of dCRT plus nimotuzumab with dCRT plus a placebo in unresectable locally advanced ESCC. 299 An interim analysis for short-term efficacy showed a significantly higher ORR (93.8 versus 72.0%) and CR rate (32.5 versus 12.2%) in nimotuzumab than the placebo. An analysis of the primary endpoint of OS is planned.…”

“…296 In contrast, two phase III trials demonstrated promising results of EGFR TKI erlotinib 297,298 and EGFR humanized mAb nimotuzumab. 299 In a phase III trial of erlotinib in combination with dCRT in ESCC, the addition of erlotinib significantly decreased locoregional recurrence and improved OS, especially in patients with EGFR overexpressing ESCC. 297,298 A phase III NXCEL1311 trial was conducted to compare the treatment efficacy of dCRT plus nimotuzumab with dCRT plus a placebo in unresectable locally advanced ESCC.…”