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

• Published in: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association Vol. 18; no. 4; pp. 824 - 832
• Main Authors: Satoh, Taroh, Lee, Kyung Hee, Rha, Sun Young, Sasaki, Yasutsuna, Park, Se Hoon, Komatsu, Yoshito, Yasui, Hirofumi, Kim, Tae-You, Yamaguchi, Kensei, Fuse, Nozomu, Yamada, Yasuhide, Ura, Takashi, Kim, Si-Young, Munakata, Masaki, Saitoh, Soh, Nishio, Kazuto, Morita, Satoshi, Yamamoto, Eriko, Zhang, Qingwei, Kim, Jung-mi, Kim, Yeul Hong, Sakata, Yuh
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01-10-2015; Springer Nature B.V
• Subjects: Abdominal Surgery; Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Adenocarcinoma - mortality; Adult; Aged; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Camptothecin - administration & dosage; Camptothecin - adverse effects; Camptothecin - analogs & derivatives; Cancer Research; Disease-Free Survival; DNA Mutational Analysis; Female; Gastric cancer; Gastroenterology; Genes, ras - genetics; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Kaplan-Meier Estimate; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - mortality; Oncology; Original; Original Article; Polymerase Chain Reaction; Receptor, Epidermal Growth Factor - biosynthesis; Receptor, Epidermal Growth Factor - genetics; Receptor, ErbB-2 - biosynthesis; Salvage Therapy - methods; Stomach Neoplasms - drug therapy; Stomach Neoplasms - genetics; Stomach Neoplasms - mortality; Surgical Oncology; Treatment Outcome; Irinotecan; Anti-EGFR; Advanced gastric cancer; Nimotuzumab; Second-line therapy
• ISSN: 1436-3291; 1436-3305
• DOI: 10.1007/s10120-014-0420-9

Background
This 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.
Methods
Irinotecan-naive patients (
n
 = 82) received N-IRI (nimotuzumab 400 mg weekly plus irinotecan 150 mg/m
2
biweekly) or IRI (irinotecan 150 mg/m
2
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.
Results
Of 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.
Conclusions
There 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.