Randomized phase II trial of nimotuzumab plus irinotecan versus irinotecan alone as second-line therapy for patients with advanced gastric cancer

Abstract

BackgroundThis multicenter, randomized phase II trial was conducted to compare the efficacy and safety of nimotuzumab plus irinotecan (N-IRI) versus irinotecan alone (IRI) in patients with advanced gastric cancer (AGC) showing disease progression after previous 5-fluorouracil-based therapy.MethodsIrinotecan-naive patients (n = 82) received N-IRI (nimotuzumab 400 mg weekly plus irinotecan 150 mg/m2 biweekly) or IRI (irinotecan 150 mg/m2 biweekly) until disease progression. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), response rate (RR), safety, tolerability, and the correlation between efficacy and tumor epidermal growth factor receptor (EGFR) expression.ResultsOf 83 patients, 40 and 43 patients were randomly assigned to the N-IRI and IRI groups, respectively. In the N-IRI/IRI treatment group, median PFS was 73.0/85.0 days (P = 0.5668), and median OS and RR at 18 months were 250.5/232.0 days (P = 0.9778) and 18.4/10.3 %, respectively. Median PFS and OS in the EGFR 2+/3+ subgroups were 118.5/59.0 and 358.5/229.5 days, respectively. The RR was 33.3/0.0 % in the N-IRI/IRI treatment group. The incidence of grade 3 or higher adverse events was 77.5/64.3 %. No adverse events of grade 3 or higher skin rash or grade 3 or higher infusion-related reaction were reported.ConclusionsThere was no superiority of N-IRI over IRI alone in terms of PFS in 5-fluorouracil-refractory AGC patients. However, N-IRI showed potential improvement in the EGFR 2+/3+ subgroup based on improved RR, PFS, and OS.

Efficacy and toxicity of nimotuzumab combined with radiotherapy in elderly patients with esophageal squamous cell carcinoma

“…A total of 10 patients received 200 mg of nimotuzumab weekly concurrently with RT, whereas the remaining 6 patients received 400 mg nimotuzumab (diluted in 250 ml 0.9% sodium chloride, administered as an intravenous infusion over 1 h) 1 week prior to the initiation of RT, followed by 200 mg once weekly concurrently with RT (19,20).…”

Targeted Therapy in Advanced Gastric Cancer: An Updated Review

“…Median overall survival improved by over 100 days. Disease control rate also improved from 33.3% to 83.3% with the addition of nimotuzumab to irinotecan [84]. These findings suggest that nimotuzumab has a role in the treatment of gastric cancer that strongly overexpresses EGFR.…”

Molecular Targeting Therapy for Gastric Cancer: Current Advances and Obstacles

“…In this study, even among the EGFR2+/3+ subgroup, adding nimotuzumab did not provide any additional benefit to the S-1 plus cisplatin combination [43]. However, nimotuzumab and irinotecan could improve survival rates in the EGFR2+/3+ subgroup [44]. The exact reasons underlying these different results according to the chemotherapy agents combined with nimotuzumab are unclear, but putative mechanisms responsible for the confusing results may be negative synergistic effects between the anti-EGFR antibody and capecitabine.…”