A post-marketing safety study of ramucirumab with FOLFIRI in patients with metastatic colorectal cancer

BackgroundRamucirumab [human vascular endothelial growth factor (VEGF) receptor-2 monoclonal antibody] + levofolinate, fluorouracil, and irinotecan (FOLFIRI) was approved for the treatment of metastatic colorectal cancer (CRC) in Japan based on the results from the phase 3 RAISE trial ({"type":"clinical-trial","attrs":{"text":"NCT01183780","term_id":"NCT01183780"}}NCT01183780). However, safety information of ramucirumab + FOLFIRI in the real-world setting is limited. Therefore, the present study was conducted to evaluate the safety of ramucirumab + FOLFIRI under routine clinical practice in patients with metastatic CRC (mCRC) after first-line chemotherapy.MethodsA single-arm, prospective, multicenter, non-interventional, observational study was conducted between August 2016 and May 2020. Patients with mCRC treated with ramucirumab + FOLFIRI for the first time were included. Patients were observed for 12 months from the start of ramucirumab. Data were recorded using the electronic data capture system.ResultsIn total, 362 patients with a mean age of 64.1 years were evaluated for safety, of whom 355 patients were evaluated for effectiveness. A higher proportion of the patients were males (n=200; 55.2%), had metastases and recurrent sites (n=362, 100.0%), and had received prior anti-cancer treatment (n=355; 98.1%). Approximately 83.7% (n=303) and 25.4% (n=92) of patients had medication history of bevacizumab and anti-epidermal growth factor receptor (EGFR) antibodies, respectively. Overall, 84.3% (n=305) of patients experienced any grade adverse events (AEs). Neutrophil count decreased (n=138; 38.1%), hypertension (n=58; 16.0%), and diarrhea (n=57; 15.7%) were observed frequently. The clinically relevant grade ≥3 AEs of special interest (AESIs) with >2% incidence included neutropenia (n=101; 27.9%), hypertension (n=35; 9.7%), proteinuria (n=23; 6.4%), hepatic dysfunction (n=15; 4.1%), febrile neutropenia (n=10; 2.8%), and leukopenia (n=9; 2.5%). The presence of renal disease at baseline increased the risk of proteinuria [risk ratio: 2.1; 95% confidence interval (CI): 1.1–4.2]. Three deaths were reported due to AEs, of which 1 was study treatment related. The 12-month survival rate of the ramucirumab + FOLFIRI regimen was 59%, mortality mainly (90%) occurring due to progressive disease.ConclusionsAlthough the current observational study enrolled patients with various medication history, the regimen of ramucirumab + FOLFIRI was manageable under clinical practice. No new safety concerns beyond the findings observed in previous clinical trials were reported.