RAMTAS: Ramucirumab Plus TAS102 Shows Survival Benefit in Specific Subgroups of Metastatic Colorectal Cancer

The RAMTAS/IKF643 trial, a phase 3 study conducted by a team of German researchers, investigated the efficacy and safety of adding ramucirumab to TAS102 (trifluridin/tipiracil) in patients with chemotherapy-refractory metastatic colorectal cancer (mCRC). This patient population had already undergone multiple lines of therapy, including oxaliplatin, irinotecan, fluoropyrimidines, and anti-EGFR or anti-angiogenic agents.

The trial aimed to determine whether ramucirumab, an antiangiogenic agent, could enhance outcomes when combined with TAS102, a standard-of-care treatment for heavily pretreated mCRC patients. The findings were presented at the European Society for Medical Oncology Congress 2024 by Stefan Kasper-Virchow, MD, of University Hospital Essen in Germany.

The trial randomized 428 patients in a 1:1 ratio to receive TAS102 alone or in combination with ramucirumab. The primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS), disease control rate (DCR), and safety.

The study did not meet its primary endpoint, with no significant improvement in OS observed between the two arms (7.46 months for ramucirumab + TAS102 vs 7.06 months for TAS102 alone; hazard ratio [HR] 0.871; P=.1941). The addition of ramucirumab demonstrated an improvement in PFS (2.37 months vs 2.07 months; HR 0.774; P=.011) and DCR (39.4% vs 31.6%; P=.0336).

Certain subgroups derived a notable survival benefit from the combination therapy; female patients and those with left-sided tumors showed improved OS with ramucirumab plus TAS102 (HR 0.712; P=.0371 and HR 0.770; P=.0469, respectively).

The combination therapy resulted in a higher incidence of grade 3 or higher treatment-related adverse events (55.9% vs 36.8%), particularly hypertension and neutropenia, necessitating more frequent dose reductions of TAS102 (40.8% vs 24.2%).

While the RAMTAS trial did not achieve its primary endpoint, it highlighted the potential benefit of adding ramucirumab to TAS102 in specific subgroups, such as female patients and those with left-sided mCRC. These findings suggest that personalized treatment approaches may optimize outcomes in patients with chemotherapy-refractory mCRC.