A Phase II study of Trifluridine/Tipiracil (FTD/TPI) in Combination with Ramucirumab in Advanced, Refractory Gastric or Gastroesophageal Junction adenocarcinomas
Mené sur 23 patients atteints d'un adénocarcinome de l'estomac ou de la jonction oesogastrique, réfractaire et de stade métastatique (âge médian : 62 ans), cet essai de phase II évalue l'efficacité, du point de vue de la survie globale à 6 mois, et la toxicité d'un traitement combinant ramucirumab et trifluridine/tipiracil
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 non-inferior to ramucirumab/paclitaxel. The trial was registered at www.clinicaltrials.gov (NCT03686488).
The Oncologist , résumé, 2025