A Real-World, Propensity-Matched Analysis of Second-Line FOLFIRI-Ramucirumab Versus Ramucirumab-Paclitaxel in Patients With Advanced Upper Gastrointestinal Cancers

Objectives: There is an urgent need for effective second line treatments for advanced upper gastrointestinal (UGI) cancers. Ramucirumab and paclitaxel (Ram-Pac) has long been the standard therapy; however, this regimen is often complicated by cumulative neuropathy. FOLFIRI-Ramucirumab (FOLFIRI-Ram) may be an alternative second line option but real-world data to support its use are limited. Methods: The deidentified Flatiron Health Research Database was queried for patients treated for unresectable or metastatic UGI cancers with second line Ram-Pac or FOLFIRI-Ram from January 2011 to June 2024. Study cohorts were propensity score matched 1:6 (FOLFIRI-Ram:Ram-Pac) from key clinical and laboratory characteristics. The endpoints of interest were overall survival (OS) and real-world time to treatment discontinuation (rwTTD). Results: Of 15,908 patients with UGI cancer, 631 received second line Ram-Pac and 40 received second line FOLFIRI-Ram. After matching, 40 FOLFIRI-Ram and 240 Ram-Pac patients were included. Median OS was 9.7 months with FOLFIRI-Ram (95% CI: 6.9-12.3) and 7.7 months with Ram-Pac (95% CI: 6.2-8.8), with a hazard ratio (HR) for death of 0.74 with FOLFIRI-Ram versus Ram-Pac (95% CI: 0.50-1.11, P =0.14). The median rwTTD with FOLFIRI-Ram was 5.2 months (95% CI: 4.1-6.2), compared with 3.7 months with Ram-Pac (95% CI: 3.2-4.3), HR for treatment discontinuation =0.70 (95% CI: 0.48-1.00, P =0.048). Conclusions: In a real-world propensity-score matched analysis, no survival difference was noted with the combination of FOLFIRI-Ram compared with Ram-Pac; however, FOLFIRI-Ram was associated with a significantly longer rwTTD. Altogether, these data suggest FOLFIRI-Ram is a potential alternative for second line treatment of UGI cancers.