Paclitaxel/Ramucirumab versus 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 days 1, 8, 15) plus ramucirumab (8 mg/kg days 1, 15) (investigational arm A) versus paclitaxel alone (80 mg/m² days 1, 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 patients; arm B 10 patients) in 9 German centers. 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. Plain Language Summary: Metastatic and unresectable ESCCs still show poor prognosis. After failure or intolerance to first-line therapy, treatment options are limited and checkpoint inhibitors are the only approved therapeutic option. Our study adds further evidence to the use of antiangiogenic drugs in second-line treatment of advanced ESCC. Ramucirumab in combination with paclitaxel showed numerically improved OS and PFS compared to paclitaxel alone. However, due to the small sample size, the results have to be considered exploratory and more data are needed in this indication. We do not recommend the use of ramucirumab/paclitaxel in second-line treatment of advanced ESCC outside of clinical trials. [ABSTRACT FROM AUTHOR]