Phase II study of FOLFIRI with low-dose irinotecan plus ramucirumab as second-line treatment in Japanese patients with metastatic colorectal cancer (Study rindo)

Objective This multicenter, single-arm, phase II study aimed to evaluate the efficacy and safety of fluorouracil, levofolinate, and irinotecan (150 mg/m², standard dose in Japan) (FOLFIRI) plus ramucirumab (RAM) as second-line treatment for metastatic colorectal cancer (mCRC) in Japanese patients. Methods On day 1 of each 2-week cycle, patients with unresectable mCRC who were refractory to oxaliplatin and fluoropyrimidine in combination with bevacizumab or anti-epidermal growth factor receptor antibodies as first-line treatment received 8 mg/kg RAM, followed by the FOLFIRI regimen with low-dose irinotecan (150 mg/m²). The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS), treatment compliance, and safety. Results A total of 62 patients were enrolled from 15 institutions between January 2018 and August 2021. The intent-to-treat and safety populations included 61 and 58 patients, respectively. Median PFS and OS were 5.9 months (95% CI, 4.8–6.9 months) and 17.0 months (95%CI, 12.0–21.0 months), respectively. The objective response rate and disease control rate were 8.2% and 74%, respectively. The median time to treatment failure was 4.8 months (95% CI, 3.2–5.9 months). Median relative dose intensities of irinotecan, 5-fluorouracil, and RAM were 73.8% (range, 40.3-102.4%), 58.5% (range, 22.8-102.4%), and 80.8% (range, 36.1-102.4%), respectively. Frequencies of Grade ≥ 3 hematologic, non-hematologic, and RAM-associated adverse events were 43%, 24%, and 17%, respectively. The observed Grade ≥ 3 adverse events included neutropenia (40%), diarrhea (8.6%), decreased appetite (10%), hypertension (6.9%), and proteinuria (3.4%). Conclusion FOLFIRI with low-dose irinotecan plus RAM is a feasible second-line treatment in Japanese patients with mCRC.