Safety and Effectiveness of Aflibercept + Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) for the Treatment of Patients with Metastatic Colorectal Cancer (mCRC) in Current Clinical Practice: OZONE Study

Abstract

For patients with metastatic colorectal cancer (mCRC) that have failed a first-line oxaliplatin-based regimen, the preferred treatment option is an irinotecan-based regimen. This prospective, observational, noncomparative, post-authorization safety study (OZONE) evaluated the safety and effectiveness of aflibercept plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) in patients with mCRC treated in daily practice after failure of an oxaliplatin-based regimen. Patients were grouped by age, renal impairment, hepatic impairment, race, number, and type of prior anticancer therapy. Of 766 treated patients enrolled, 59.5% were male, 94.8% had an Eastern Cooperative Oncology Group performance status of 0-1, all received previous chemotherapy (97.8% including oxaliplatin), and 58.6% had prior exposure to bevacizumab. At least one grade ≥ 3 treatment-emergent adverse event (TEAE) was reported in 68.3% of patients. Neutropenia, hypertension, diarrhea, and asthenia were the most frequently occurring grade ≥ 3 TEAEs. Antivascular endothelial growth factor class events were infrequent. Subgroup analyses did not reveal major differences in the safety profile according to age, renal and hepatic status, race, or prior anticancer therapy. For the total population, median overall survival was 12.5 months, median progression-free survival was 6.1 months, and overall response rate was 16.3%. Aflibercept in combination with FOLFIRI is a safe and efficacious regimen administered in current clinical practice to patients with mCRC previously treated with oxaliplatin. The study results, conducted in real-world clinical practice with a less selected patient population, are aligned with the VELOUR (NCT00561470) trial and no new safety issues were identified.

Keywords: FOLFIRI; aflibercept; antiangiogenic; clinical practice; metastatic colorectal cancer; observational.

Conflict of interest statement

IC has participated in advisory boards for Eli-Lilly, Bristol-Myers Squibb, MSD, Bayer, Roche, Merck Serono, Five Prime Therapeutics, Astra Zeneca, Oncologie International, and Pierre Fabre, has received research funding from Eli-Lilly, Janssen-Cilag, Sanofi Oncology, and Merck Serono, and has received honorarium from Eli-Lilly. MF has received personal fees from Amgen, Array BioPharma, and Bayer, has received grants from Amgen, Astra Zeneca, and Novartis, and has received personal fees from Seattle Genetics. PG-A has participated in advisory boards for Amgen, Bristol-Myers Squibb, MSD, Roche, Merck Serono, Sanofi Oncology, Ipsen, and Servier. ZL received personal fees from Sanofi, Amgen, and Servier, and travel support from Merck. ARC has received personal fees from Servier, Sanofi, Amgen, Merck, Eli-Lilly, Roche, Medtronic, and BTG, and grants from Sanofi. EPM has received personal fees from Roche, Amgen, Sanofi, and Merck Serono. PP is employed by Ividata on behalf of Sanofi. MC is employed by Sanofi. TC has received personal fees from Amgen and Taiho.

Figures

Figure 1

Overall survival (A) for the overall treated population; (B) according to age (< 65/≥ 65 years); (C) according to renal impairment (yes/no); (D) according to hepatic impairment (yes/no); (E) according to race (Caucasian/non-Caucasian); (F) according to prior anticancer therapy (0–1/> 1 lines); (G) according to prior use of bevacizumab (yes/no).CI, confidence interval; HI, hepatic impairment; HR, hazard ratio; OS, overall survival; RI, renal impairment.

Figure 2

OZONE summary of overall response rate.CR, complete response; NE, not evaluable; PD, progressive disease; PR, partial response; SD, stable disease.