1535P - Paclitaxel + ramucirumab versus paclitaxel alone in patients with squamous-cell carcinoma of the oesophagus, refractory or intolerant to combination therapy with fluoropyrimidine and platinum-based drugs: Final results from the randomized phase II IKF-S627/RAMOS trial of the AIO

Background

Ramucirumab (Ram) combined with docetaxel is an approved 2^nd-line treatment in patients (pts) with squamous cell carcinoma (SCC) of the lung (REVEL study) and with paclitaxel for esophagogastric adenocarcinoma (RAINBOW study). In SCC of the oesophagus, nivolumab is currently the only evidence-based 2^nd-line treatment option. This study evaluates the safety and efficacy of Ram plus paclitaxel.

Methods

This prospective, randomized, open-label, multicentre, phase II trial evaluated paclitaxel plus Ram (Ram 8 mg/kg d1, 15 and paclitaxel 80 mg/m² d1, 8, 15) Arm A vs. paclitaxel alone (80 mg/m² d1, 8, 15) Arm B, both q4w. Primary endpoint was overall survival rate at 6 months (mos) (OS@6), main secondary endpoints were OS, PFS, objective response rate (ORR) and safety.

Results

From 3/2019 to 4/2021, 21/186 planned pts were treated within the study protocol (Arm A 11 pts; Arm B 10 pts) in 9 German centres. Due to slow accrual, the study was terminated prematurely. Median age was 63y, 71% were male and 86% had relevant concomitant disease. Pts received a median of 9 and 10 cycles in Arms A and B, respectively. Median follow-up was 9 mos (0.7 – 32.4 mos). OS@6 in Arm A was 73% for Ram/paclitaxel and 50% for paclitaxel. However, the study design did not allow for statistical comparison of the arms. ORR (CR+PR 18% vs. 20%) and DCR (CR+PR+SD 55% vs. 60%) were in the same range, as well as median PFS (3.8 vs. 3.5 mos) and OS (12.1 vs. 9.2 mos) for Arms A and B, respectively. The most common treatment related adverse events (AEs) in Arm A were leucopoenia (55%), fatigue (27%) and peripheral sensory neuropathy (18%). Treatment related AEs ≥ grade 3 occurred in 27% in Arm A and 50% in Arm B. Serious AEs (SAEs) occurred in 36% and 50% in Arms A and B, respectively.

Conclusions

Ram and Paclitaxel shows an acceptable tolerability and numerically improved OS@6. Due to the small number of pts the current trial must be considered exploratory, and more data are needed in this indication.

Clinical trial identification

NCT03762564.

Editorial acknowledgement

Legal entity responsible for the study

Institut für Klinische Krebsforschung IKF am Krankenhaus Nordwest.

Funding

Lilly Deutschland GmbH.

Disclosure

T.O. Goetze: Other, Advisory Role: Lilly, MSD Oncology, Bayer, Servier, Roche, Novartis, Incyte, Foundation Medicine, Bristol Myers Squibb; Other, Speaker’s Bureau: Lilly; Financial Interests, Research Funding: Deutsche Forschungsgemeinschaft, Gemeinsamer Bundesausschuss, Deutsche Krebshilfe, Lilly, AstraZeneca, Incyte. T.J. Ettrich: Other, Advisory Role: Eisai, MSD Oncology, Bayer, Roche, Sanofi, Bristol Myers Squibb, Incyte, AstraZeneca, Merck, Pierre Fabre, Servier, Lilly, Ipsen, BMS GmbH & Co. KG, Daiichi Sankyo Europe GmbH; Financial Interests, Other, Travel, Accommodations, Expenses: Ipsen; Financial Interests, Research Funding: Baxalta/Shire. H. Schmalenberg: Other, Advisory Role: Lilly, Novartis, BMS GmbH & Co. KG, MSD, Merck. R.J.C. Mahlberg: Other, Advisory Role: AstraZeneca. G. Hapke: Financial Interests, Research Funding: MSD, Bristol Myers Squibb, Gilead Sciences, BioNTech. P.C. Thuss-Patience: Other, Advisory Role: Bristol Myers Squibb, Merck, Lilly, Novartis, Pfizer, Roche, AstraZeneca, Daiichi Sankyo, Astellas Pharma, MSD, Servier; Financial Interests, Research Funding: Merck/Pfizer. S. Al-Batran: Other, Advisory Role: Lilly, Bristol Myers Squibb, Merck Sharp & Dohme, MacroGenics, AstraZeneca, Daiichi Sankyo; Other, Speaker’s Bureau: Lilly, AIO GmbH, Bristol Myers Squibb, MCI Group; Financial Interests, Stocks or ownership: Institut für Klinische Krebsforschung GmbH, Immutep; Financial Interests, Research Funding: Celgene, Lilly, Medac, Hospira, Sanofi, German Cancer Aid, German Research Foundation, Federal Ministry of Education and Research, Roche, Vifor Pharma, Eurozyto, Immutep, Ipsen, Bristol Myers Squibb, Merck Sharp & Dohme, AstraZeneca. All other authors have declared no conflicts of interest.