Ramucirumab plus irinotecan / leucovorin / 5-FU versus ramucirumab plus paclitaxel in patients with advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction, who failed one prior line of palliative chemotherapy: the phase II/III RAMIRIS study (AIO-STO-0415)

• Published in: BMC cancer 2023-06, Vol.23 (1), p.561-8, Article 561
• Main Authors: Lorenzen, Sylvie, Schwarz, Alix, Pauligk, Claudia, Goekkurt, Eray, Stocker, Gertraud, Knorrenschild, Jorge Riera, Illerhaus, Gerald, Dechow, Tobias, Moehler, Markus, Moulin, Jean-Charles, Pink, Daniel, Stahl, Michael, Schaaf, Marina, Goetze, Thorsten Oliver, Al-Batran, Salah-Eddin
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - pathology; Antimitotic agents; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Camptothecin; Cancer; Care and treatment; Chemotherapy; Chemotherapy, Combination; Clinical trials; Dosage and administration; Drug therapy; Esophageal cancer; Esophagogastric Junction - pathology; Fluorouracil; FOLFIRI; Humans; Irinotecan; Leucovorin; Metastasis; Metastatic esophagogastric adenocarcinoma; Paclitaxel; Quality of Life; Ramucirumab; Second line treatment; Stomach cancer; Stomach Neoplasms - pathology; Study Protocol; Testing
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-023-11004-z

Paclitaxel in combination with ramucirumab is the standard of care second-line therapy in gastro-esophageal adenocarcinoma (GEA). As the number of taxane pretreated patients in the perioperative or first-line setting is increasing, it is unknown whether these patients benefit from re-applying a taxane in using the combination of paclitaxel and ramucirumab. Furthermore, the rates of neurotoxicity with first-line FOLFOX or FLOT range from 30%-70%, making second-line taxane-containing therapy less suitable to a meaningful portion of patients. This patient group is likely to benefit from a taxane-free second-line chemotherapy regimen, such as FOLFIRI and ramucirumab (FOLFIRI-Ram). Therefore, the RAMIRIS phase III trial evaluates the effects of the regimen of FOLFIRI-Ram in the second-line treatment after a taxane-based chemotherapy in patients with advanced GEA. The RAMIRIS trial is a randomized, open-label, multicenter phase II/III study comparing treatment of FOLFIRI-Ram (arm A) with paclitaxel and ramucirumab (arm B). The Phase II is already closed with 111 enrolled patients. In the phase III, 318 taxane-pretreated patients with advanced GEA will be recruited and randomized 1:1 to FOLFIRI (5-FU 2400 mg/m over 46 h i.v., irinotecan 180 mg/m i.v.; 5-FU 400 mg/m bolus; leucovorin 400 mg/m i.v.; on day 1 and 15, q28) with ramucirumab 8 mg/kg every two weeks (Arm A) or paclitaxel 80 mg/m (days 1, 8, 15, q28) with ramucirumab 8 mg/kg every two weeks (Arm B). The primary endpoints are overall survival (OS) and objective overall response rate (ORR). Secondary endpoints are progression-free survival (PFS), disease control rate and safety and quality of life as assessed by EORTC-QLQ-C30 questionnaire. The already completed RAMIRIS phase II demonstrated feasibility and efficacy of FOLFIRI-Ram. Especially docetaxel-pretreated patients seemed to markedly benefit from FOLFIRI-Ram, with favorable response- and PFS rates and lower toxicity. This offers a rationale for the phase III trial. If the RAMIRIS III trial transfers and confirms the results, they will affect the current treatment guidelines, recommending the combination therapy of FOLFIRI-Ram for taxane-pretreated patients with advanced GEA. NCT03081143 Date of registration: 13.11.2015.