Ramucirumab, FOLFIRI combination shows promise in gastroesophageal adenocarcinoma

CHICAGO — An interim analysis of data from the phase 2 RAMIRIS trial suggests that a combination regimen of FOLFIRI plus ramucirumab is a feasible second-line treatment option for patients with advanced or metastatic gastroesophageal adenocarcinoma, according to researchers at the ASCO Annual Meeting.

FOLFIRI (fluorouracil, leucovorin and irinotecan) plus ramucirumab (Cyramza, Eli Lilly) was associated with fewer serious treatment-related adverse events, as well as an improvement in overall objective response (ORR) and disease control compared with ramucirumab plus paclitaxel in patients who received first-line treatment with docetaxel, Sylvie Lorenzen, MD, of Klinikum Rechts der Isar in Munich, Germany, and colleagues reported.

“Ramucirumab as monotherapy and in combination with paclitaxel is a proven second-line option for advanced gastroesophageal adenocarcinoma (GEA),” the researchers wrote. “More and more patients are pretreated with docetaxel in the perioperative or first-line setting. For those patients, the benefit of a combination of ramucirumab and paclitaxel is unclear, and physicians would choose an irinotecan-based regimen as second-line treatment. This provides a rationale for the evaluation of FOLFIRI plus ramucirumab.”

Lorenzen and colleagues randomly assigned patients with advanced GEA in a 2:1 ratio to receive FOLFIRI plus ramucirumab every two weeks or paclitaxel (days 1, 8 and 15 of a 28-day cycle) plus ramucirumab every 2 weeks. During an interim analysis, the researchers assessed the safety of FOLFIRI plus ramucirumab in 58 patients and ORR rate in 50 patients.

The main grade 3 or higher adverse events included neutropenia, fatigue and diarrhea. In the FOLFIRI plus ramucirumab arm, 20% of patients experienced neutropenia, 6% experienced fatigue and 8% experienced diarrhea. In the paclitaxel plus ramucirumab arm, 22% of patients experienced neutropenia and 3% experienced diarrhea. There were no reports of fatigue in this group.

Serious treatment-related adverse events occurred in 14% of patients who received FOLFIRI plus ramucirumab arm vs. 23% of patients who received paclitaxel plus ramucirumab.

In an efficacy analysis limited to patients who previously received docetaxel (58%), FOLFIRI plus ramucirumab was associated with an ORR rate of 30% and disease control rate (DCR) of 65%. In contrast, paclitaxel plus ramucirumab was associated with an ORR rate of 8% and DCR of 50%.

“The interim safety analysis of the RAMIRIS trial has demonstrated the feasibility of the combination of FOLFIRI and ramucirumab,” the researchers concluded. “Docetaxel-pretreated patients had higher ORR and DCR when ramucirumab was combined with FOLFIRI instead of paclitaxel. A phase 3 trial will start soon to confirm this finding.” – by Stephanie Viguers

Reference:

Lorenzen S, et al. Abstract 4023. Presented at: ASCO Annual Meeting; May 31- June 4, 2019; Chicago.

Disclosures: Lorenzen reports receiving honoraria and research funding from Eli Lilly and Company and serving in consulting or advisory roles for Celgene, Eli Lilly and Company, MSD Oncology, Sanofi/Aventis and Servier Laboratories. Please see the abstract for all other authors’ relevant financial disclosures.