RAMucirumab in combination with TAS102 versus TAS102 monotherapy in metastatic colorectal cancer: Safety results from the phase IIb part of the RAMTAS phase II/III trial of the German AIO (AIO-KRK-0316).

Abstract

3566 Background: Patients (pts) with mCRC progressing on standard chemotherapy have limited therapeutic options. Trifluridine/tipiracil (TAS102) significantly improved survival in patients with refractory mCRC. Ramucirumab (ram) is approved in combination with FOLFIRI for second-line treatment. There is a strong rationale to evaluate the efficacy and safety of ram in combination with TAS102 in pts with refractory mCRC. Methods: This is a randomized, open-label, multicenter, starting as phase IIb and extended to a phase III study in pts with advanced mCRC. Eligible pts were randomized to receive either ram (8 mg/kg on d1+15, q4w) and TAS102 (35 mg/m² on d1-5 and d8-12, q4w, arm A) or TAS102 alone (arm B). The primary endpoint is overall survival. A total of 145 pts were enrolled into phase IIb. Here, we present the data from an interim safety analysis comprising the first 80 treated pts. The trial was extended to phase III including a total of 426 pts. Enrolment of additional 281 pts started in Dec 2020. The trial endpoints remained unchanged. Results: Pts (40 arm A, 40 arm B) received a median of 2.5 treatment cycles in arm A and 2 cycles in arm B; 31 pts in treatment arm A and 32 pts in arm B discontinued participation prematurely, mainly due to cancer progression. Most patients developed adverse events (AEs): grade 3 AEs were observed in 28 pts (70%) in arm A (24 treatment-related) and 27 pts (67%, 17 treatment-related) in arm B. More grade 4 AEs were seen in arm A (13 pts, 32.5%) than in arm B (5 pts, 12.5%). In total, 46 Serious AEs (SAEs) occurred, 27 in arm A (10 treatment-related) and 19 in Arm B (2 treatment-related). Five SAEs (3 in arm A, 2 in arm B) had a fatal outcome (one in arm A treatment-related). Within the analyzed population, no SUSAR occurred. Conclusions: This safety analysis demonstrates a minor increase in AEs in the experimental arm but no unexpected events. There were no excessive toxicity or unacceptable risks. In summary, a favorable risk-benefit-profile was confirmed. Based on these safety results and the ongoing need for efficient treatment in the tested population, the trial was extended to phase III. Clinical trial information: NCT03520946.