Clinical experience: FOLFIRI/XELIRI after failure of a fluoropyrimidine/platinum combination regimen in advanced gastroesophageal adenocarcinoma.
Authors: Leão Inês , Marinho Joana Catarina Lima , Neto Ema Silva , Guedes Helena , Joaquim Ana , Moreira Pinto António , Dias Enrique , Costa Telma , Custódio Sandra , Capela Andreia 
Published: June 2021

e16104 Background: Portugal has the highest gastric cancer incidence in western Europe. In our institution, FOLFIRI/XELIRI is the standard second line (2L) chemotherapy (CT) in advanced gastroesophageal adenocarcinoma (aGEA). Other treatment option is paclitaxel/ramucirumab combination. There is no prospective trial comparing these regimens. Our global aim was to investigate efficacy and safety of FOLFIRI/XELIRI after failure of a fluoropyrimidine/platinum (FP) regimen in patients with aGEA. Methods: Single center, retrospective cohort study of all patients with aGEA who failed FP regimen and received > 1 cycle of FOLFIRI/XELIRI between 2015-2020. Failure of a FP regimen defined as: 1) progression after first line (1L) palliative CT; 2) progression < 6 months after a curative intent strategy. Kaplan-Meier method was used to estimate median overall (mOS) / progression free survival (mPFS) and multivariate Cox regression analysis to assess PFS predictors. Results: Thirty-three patients analyzed. FOLFIRI/XELIRI regimen was used as 1L palliative CT (after failure of curative intent CT) in 48.5% of patients and as 2L palliative CT in 51.5%. Median age was 63 years (IQR 54–68.5), 72.7% were men. ECOG performance status (ECOG-PS) was 0-1 in 84.8%. Primary tumor site was stomach (87.9%), gastroesophageal junction (9.1%), esophagus (3.0%). All but one patient had metastatic disease (57.6% ≥2 metastatic sites; 42.4% peritoneal disease). Histology subtypes identified were diffuse and intestinal (14 patients each). Signet ring cell features were present in 12,1% of cases. 6 had HER2 positive tumors and in 1 there was microsatellite instability. 30,3% of patients had surgery of the primary tumor. Median number of cycles was 12 (IQR 5–17.5). Tumor response was accessed in 27 patients. Disease control rate was 74,1% (1 complete response, 8 partial responses, 11 stable disease). With a median follow-up of 9.4 months, mPFS was 5.1 months (95%CI 4.3-5.9) and the mOS 9.8 months (95%CI 6.6-13.0). 6-month overall survival was 69.7%. In multivariate analysis ECOG-PS (HR 6.20, p = 0.002), age (HR 0.94, p = 0.011), pre-treatment level CEA (HR 1.01, p = 0.011) and FOLFIRI/XELIRI as 1L palliative CT (HR 0.25 p = 0.004) were predictors of PFS. Treatment was discontinued in 31 patients (20 disease progression, 10 worsening of ECOG-PS). The main treatment-related grade 3 or 4 adverse events were neutropenia (12.1%), mucositis (9.1%) and anemia (6.6%). No treatment-related deaths occurred. Fifteen patients initiated a subsequent treatment line (7 taxane, 2 ramucirumab, 5 taxane/ramucirumab, 1 Tas102). Conclusions: FOLFIRI is an active and well tolerated regimen after failure of a FP regimen in patients with aGEA. Population with poor prognostic features was well represented. Efficacy outcomes were similar to the ones reported for the paclitaxel/ramucirumab combination RAINBOW trial.