Results from a single-arm phase 2 study show ramucirumab plus irinotecan yields promising antitumor activity and safety results in patients with advanced gastric cancer.
Gastric cancer is among the leading causes of cancer-related mortality worldwide. The incidence of gastric cancer is higher in East Asia, Eastern Europe, and South America, with diet, obesity, gastroesophageal reflux disease, and Helicobacter pylori infection associated with occurrence.1 Heredity and environmental factors have also been linked to the development of gastric cancer.1 Many patients with gastric cancer are initially diagnosed with advanced gastric cancer, which, despite treatment, has a poor prognosis.1 There is an urgent need for effective treatments of metastatic gastric cancer, with ongoing clinical trials researching various systemic treatments.
One medication under investigation is ramucirumab, a fully human immunoglobulin G1 monoclonal VEGF receptor-2 antibody. VEGF binds to VEGF receptors, initiating the development of new blood vessels in tumors.2 Ramucirumab binds to VEGF receptors on cells to prevent VEGF binding, thereby slowing the proliferation and growth of tumors.2 In the RAINBOW clinical trial, ramucirumab combined with paclitaxel increased overall survival (OS) in patients with advanced pretreated gastric cancer compared with treatment with paclitaxel alone. The WJOC 4007 trial combining paclitaxel with irinotecan found this combination also increased OS for patients with advanced pretreated gastric cancer.
Building on these trial results, a nonrandomized single-arm phase 2 clinical trial enrolling 35 patients was conducted in Japan to evaluate the use of ramucirumab and irinotecan as second-line therapy in patients with advanced gastric cancer. The patients ranged from 47 to 80 years of age. There were 25 males and 10 females enrolled in this clinical trial, with patient Eastern Cooperative Oncology Group performance scores of 0 or 1. The primary study end point was 6-month progression-free survival (PFS), with secondary end points of OS, PFS, response rate, and safety. At 6 months, the PFS was 26.5% with a median PFS of 4.2 months and OS of 9.6 months. The response rate was 26% with a disease control rate of 85%. Analysis of adverse events (AEs) found that grade ≥3 AEs occurred in 5% of the patients. The most common AE was neutropenia followed by, in decreasing occurrence, leukopenia, anemia, anorexia, febrile neutropenia, diarrhea, hypertension, proteinuria, hypokalemia, hypoalbuminemia, thrombocytopenia, and hyponatremia. All AEs were considered to be manageable.
Ramucirumab and irinotecan combination therapy demonstrated promising antitumor activity and safety results in patients with advanced gastric cancer.
Source: Kawamoto Y, Yuki S, Sawada K, et al. Results of a phase 2 trial of ramucirumab plus irinotecan as second-line treatment for patients with advanced gastric cancer (HGCSG 1603). J Clin Oncol. 2021;30(suppl_3):217.
References
- Siebenhüner AR, De Dosso S, Helbling D, et al. Advanced gastric cancer: current treatment landscape and a future outlook for sequential and personalized guide: Swiss expert statement article. Oncol Res Treat. 2021;44:485-494.
- American Cancer Society. Targeted drug therapy for stomach cancer. Updated January 22, 2021. www.cancer.org/cancer/stomach-cancer/treating/targeted-therapies.html. Accessed October 10, 2021.