Continuing ramucirumab in combination with trifluridine/tipiracil (TAC-102) beyond progression for patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma demonstrated a favorable safety profile and promising efficacy, according to data from a phase 2 study presented at 2023 ASCO Gastrointestinal Cancers Symposium.

Results from previous trials have suggested that combining ramucirumab beyond progression with trifluridine/tipiracil may be beneficial for this patient population. The RE-ExPEL trial aimed to investigate the tolerability, safety, and benefit of this treatment regimen.

This multicenter, non-randomized, open-label, single arm pilot trial enrolled 20 patients with advanced gastric or GEJ adenocarcinoma pretreated with ramucirumab between October 2020 and August 2021 (20% gastric cancers, 80% GEJ cancers). Most patients received the study medication in the third-line setting (90%), with the rest in further lines of treatment.

Patients received 8 mg/kg ramucirumab every 2 weeks plus 35 mg/m² trifluridine/tipiracil twice a day for a maximum of 4 cycles. The primary end point was tolerability and toxicity with secondary end points including efficacy data, overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).

There was at least 1 serious adverse event reported in 25% of patients, with 9 total serious adverse events. There was 1 fatal outcome. All serious adverse events were without relationship to systemic therapy and there were no suspected unexpected serious adverse reactions. The median OS was 9.07 months and the DCR was 45%.

Limitations of this trial include the small number of patients enrolled and the single arm design.

Study authors concluded, “safety data showed a favorable safety profile with a low rate of severe toxicity” …adding there was “very promising efficacy data for the combination” and the combination of ramucirumab plus trifluridine/tipiracil “seems to be more effective than TAS-102 alone.” Further evaluation via a randomized phase 3 trial is needed.

Source:

Goetze TO, Stein A, Lorenzen S, et al. Ramucirumab beyond progression plus TAS 102 in patients with advanced or metastatic adenocarcinoma of the stomach or the gastroesophageal junction, after treatment failure on a ramucirumab-based therapy: Final results of the phase II RE-ExPEL study. Presented at 2023 ASCO Gastrointestinal Cancers Symposium; January 19-21, 2023; San Francisco, CA. Abstract 359