A phase II study of trifluridine/tipiracil in combination with ramucirumab in advanced, refractory gastric, or gastroesophageal junction adenocarcinomas.

BACKGROUND: Ramucirumab plus paclitaxel after progression on fluoropyrimidine/platinum in metastatic gastric (GA) and gastroesophageal junction adenocarcinoma (GEJC) has shown improvement in overall survival over paclitaxel alone. However, the incidence of neuropathy was 46%. Therefore, there is an unmet need for novel treatment to minimize the long-term toxicity of neuropathy. We conducted a single arm phase II study of ramucirumab and trifluridine/tipiracil (FTD/TPI) in metastatic GA/GEJC. METHODS: Patients received ramucirumab at 8 mg/kg intravenously on day 1 and 15, and FTD/TPI at 35 mg/m2 orally twice daily on days 1-5 and days 8-12 on every 28-days cycle. The primary endpoint was 6-months overall survival (OS) rate and secondary endpoints were progression free survival (PFS), objective response rate and safety. RESULTS: At data cut-off of August 15, 2021, 23 pts were enrolled. The median age was 62 years. Most common treatment-related toxicities were diarrhea (39%), fatigue (39%), hypertension (39%), and nausea (35%). Most common treatment related Grade 3 or 4 adverse events were neutropenia (17%) and anemia (13%). The median PFS and OS was 4.8 and 6.1 months, respectively. The 6-month OS rate was 57% (95% CI: 36.4%-79.8%). Of the 18 evaluable patients with at least one post-baseline imaging, 2 (11%) patients demonstrated objective partial response, and 15 (83%) had stable disease. CONCLUSION: The combination of ramucirumab and FTD/TPI demonstrated well-manageable safety profile. Our study did not meet primary endpoint. Ongoing clinical trials will help us understand if ramucirumab plus FTD/TPI is noninferior to ramucirumab/paclitaxel. The trial was registered at www.clinicaltrials.gov (NCT03686488).