Initial Report of Second‐Line FOLFIRI in Combination with Ramucirumab in Advanced Gastroesophageal Adenocarcinomas: A Multi‐Institutional Retrospective Analysis

BACKGROUND. The randomized phase III RAINBOW trial established paclitaxel (pac) plus ramucirumab (ram) as a global standard for second‐line (2L) therapy in advanced gastric and gastroesophageal junction adenocarcinoma, together gastroesophageal adenocarcinoma (GEA). Patients (pts) receiving first‐line (1L) FOLFOX often develop neuropathy that renders continued neurotoxic agents in the 2L setting unappealing and other regimens more desirable. As such, FOLFIRI‐ram has become an option for patients with 2L GEA. FOLFIRI‐ramucirumab (ram) has demonstrated safety and activity in 2L colorectal cancer, but efficacy/safety data in GEA are lacking. SUBJECTS, MATERIALS, AND METHODS. Patients with GEA treated with 2L FOLFIRI‐ram between August 2014 and April 2018 were identified. Clinicopathologic data including oxaliplatin neurotoxicity rates/grades (G), 2L treatment response, progression‐free survival (PFS), overall survival (OS), safety, and molecular features were abstracted from three U.S. academic institutions. Kaplan‐Meier survival analysis was used to generate PFS/OS; the likelihood ratio test was used to determine statistical significance. RESULTS. We identified 29 pts who received 2L FOLFIRI‐ram. All pts received 1L platinum + fluoropyrimidine, and 23 of 29 (79%) had post‐1L neuropathy; 12 (41%) had G1, and 11 (38%) had G2. Patients were evenly split between esophagus/gastroesophageal junction (12; 41%) and gastric cancer (17; 59%). Among evaluable pts (26/29), the overall response rate was 23% (all partial response) with a disease control rate of 79%. Median PFS was 6.0 months and median OS was 13.4 months among all evaluable pts. Six‐ and 12‐month OS were 90% (n = 18/20) and 41% (n = 7/17). There were no new safety signals. CONCLUSION. We provide the first data suggesting FOLFIRI‐ram is a safe, non‐neurotoxic regimen comparing favorably with the combination of pac + ram used in the seminal RAINBOW trial. IMPLICATIONS FOR PRACTICE. Results of this study provide initial support for the safety and efficacy of second‐line (2L) FOLFIRI‐ramucirumab (ram) after progression on first‐line platinum/fluoropyrimidine in patients with gastroesophageal adenocarcinoma (GEA). The overall response, progression‐free survival, overall survival, and toxicity profile compare favorably with paclitaxel (pac) + ram and highlight the importance of the ongoing phase II RAMIRIS trial examining FOLFIRI‐ram versus pac + ram in 2L GEA (NCT03081143). FOLFIRI‐ram may warrant consideration for inclusion as an alternate regimen in consensus guidelines for GEA.