Paclitaxel/Ramucirumab vs. Paclitaxel in 2nd-line therapy of advanced esophageal squamous cell carcinoma: Randomized Phase II IKF-AIO-RAMOS Trial.

INTRODUCTION In squamous cell carcinoma of the esophagus (ESCC), therapeutical options in 2nd-line treatment are scarce with immune checkpoint inhibition being the only approved one. Ramucirumab/paclitaxel is an approved 2nd-line treatment in metastatic esophagogastric adenocarcinoma. We assessed safety and efficacy of ramucirumab/paclitaxel for ESCC. METHODS This prospective, randomized, open-label, multicenter, phase II trial evaluated paclitaxel (80 mg/m2 d1, 8, 15) plus ramucirumab (8 mg/kg d1, 15) (investigational arm A) vs. paclitaxel alone (80 mg/m2 d1, 8, 15) (standard arm B), both q4w, in advanced/metastatic ESCC refractory or intolerant to fluoropyrimidine and platinum-based drugs. Primary endpoint was overall survival (OS) rate at 6 months. RESULTS From 3/2019 to 4/2021, 21/186 planned patients were included (arm A 11 pts; arm B 10 pts) in 9 German centres. Due to slow accrual, the study was terminated prematurely. OS at 6 months was 72.7% for ramucirumab/paclitaxel and 50.0% for paclitaxel. The study design did not allow statistical comparison of the arms. PFS (3.8 vs. 3.5 months), OS (12.1 vs. 9.2 months), ORR (18.2% vs. 20.0%) and DCR (54.5% vs. 60.0%) were comparable in both arms. Most common treatment related adverse events (TRAEs) in arm A were leucopenia (54.5%), fatigue (27.3%) and peripheral sensory neuropathy (18.2%). 27.3% in arm A and 50.0% in arm B had TRAEs ≥ grade 3. CONCLUSION Ramucirumab/paclitaxel shows an acceptable tolerability and numerically improved OS at 6 months. Due to the small number of patients the current trial must be considered exploratory and more data are needed in this indication. REGISTRATION ClinicalTrials.gov, NCT03762564. IKF-s627 RAMOS Study.