Post-Marketing Safety Study of Ramucirumab Plus FOLFIRI: Analysis of Age and Initial Dose of Irinotecan in Patients with Metastatic Colorectal Cancer

BackgroundThere is limited real-world evidence regarding the safety of ramucirumab plus FOLFIRI in patients with metastatic colorectal cancer (mCRC).ObjectiveWe evaluated the safety of ramucirumab plus FOLFIRI in patients with mCRC by age and initial dose of irinotecan.Patients and MethodsThis single-arm, prospective, multicenter, non-interventional, observational study was conducted between December 2016 and April 2020. Patients were observed for 12 months.ResultsOf 366 enrolled Japanese patients, 362 were eligible for study inclusion. The frequency of grade >= 3 adverse events (AEs) by age (>= 75 years vs < 75 years) was 56.1% versus 50.2%, indicating no substantial differences between age groups. Grade >= 3 notable AEs, including neutropenia, proteinuria, and hypertension, were also similar in both age groups, but the frequency of any grade venous thromboembolic events was higher in those aged >= 75 years than in those aged < 75 years (7.0% vs 1.3%). The frequency of grade >= 3 AEs was slightly lower in patients receiving > 150 mg/m(2) of irinotecan than in those receiving <= 150 mg/m(2) of irinotecan (42.1% vs 53.6%); however, the frequency of grade >= 3 diarrhea, but not any grade diarrhea, and liver failure/injury was higher in patients receiving > 150 mg/m(2) of irinotecan than in those receiving <= 150 mg/m(2) of irinotecan (4.6% vs 1.9% and 9.1% vs 2.3%, respectively).ConclusionsThe safety profile of ramucirumab plus FOLFIRI in mCRC patients was similar in subgroups by age and initial irinotecan dose in real-world settings. Plain Language SummaryColorectal cancer (CRC), also known as bowel cancer, is a common cancer and a leading cause of death. Chemotherapy is a treatment option for CRC. It consists of one or more powerful medications to destroy cancer cells with the aim of prolonging life and reducing symptoms. These medications can cause side effects such as nausea, vomiting, infections, and high blood pressure. Sometimes these side effects can be so severe that patients stop or reduce their treatment. The safety and efficacy of these anti-cancer drugs are established from clinical trials, but, in daily clinical practice, patient outcomes are affected by various factors, such as general health, age, prior treatments, and lifestyle. Ramucirumab plus FOLFIRI is considered a standard treatment for CRC in patients who have disease progression after first-line treatment. In this study, we collected data from patients with CRC who were given ramucirumab plus FOLFIRI under routine clinical practice in Japan. Data were collected for 12 months from the start of treatment and based on various patient demographics such as age less than or greater than 75 years and treatment with a lower or higher dose of the anti-cancer drug irinotecan. We found that ramucirumab plus FOLFIRI is manageable in patients with CRC regardless of these patient demographics and initial irinotecan dose. This article aims to inform patients and primary care providers regarding real-world treatment outcomes to assist with CRC treatment decision making.