RECAST: Updated Analysis of FOLFIRI, Ramucirumab Versus FOLFOXIRI, Ramucirumab for Metastatic CRC

The latest data from the RECAST trial shed light on the comparative effectiveness of FOLFIRI plus ramucirumab (RAM) versus FOLFOXIRI plus RAM as first-line treatment options for patients with metastatic colorectal cancer (CRC).

Results are presented at the European Society for Medical Oncology (ESMO) Congress 2024.

At ESMO Congress 2022, the results of the randomized phase 2 RECAST study comparing FOLFIRI plus RAM versus FOLFOXIRI plus RAM for patients with previously untreated metastatic CRC were reported. The confirmed objective response rate (ORR, 57.6% vs 60.3%, respectively) and median progression-free survival (PFS, 11.7 months vs 10.5 months, respectively) were similar, and overall survival (OS) data were immature.

In RECAST, 122 patients were randomized to FOLFIRI plus RAM (arm A; n=59) or eight cycles of FOLFOXIRI plus RAM followed by 5-FU/l-leucovorin plus RAM (arm B; n=63) from June 2017 to September 2020. Treatment was repeated every 2 weeks until disease progression or unacceptable toxicity.

Researchers noted that patient characteristics were similar across treatment arms with the exception of liver-limited disease, which was higher in arm A (32% vs 19%, respectively).

After a median follow-up of 42.1 months for arm A and 40.4 months for arm B, the median OS was 32.5 months (95% CI, 26.8-36.5) and 28.2 months (95% CI, 21.9-31.2), respectively (HR, 1.58; P=.003).

After treatment, R0 resection, radiotherapy, and chemotherapy were performed as subsequent treatment in both arms. In a biomarker analysis combining patients from both arms, no relationship was found between the OS and VEGF-D levels at pre- and post-treatment. Patients with high IL-8 level at post-treatment had shorter OS compared with those with low IL-8 level (29.3 months vs 31.6 months, respectively; HR, 0.60; P=.049), researchers reported, and patients with increased heparin-binding EGF-like growth factor level from pre-treatment to cycle 2 had longer OS compared with those with decreased heparin-binding EGF-like growth factor level (34.3 months vs 28.2 months, respectively; HR, 1.78; P=.024).

“[RECAST] did not show the superiority of FOLFOXIRI plus RAM in terms of OS, ORR, and PFS compared with FOLFIRI plus RAM as first-line treatment for metastatic CRC,” they concluded.