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Ramucirumab beyond progression plus TAS-102 in patients with advanced or metastatic esophagogastric adenocarcinoma, after treatment failure on a ramucirumab-based therapy – final results of the phase II RE-ExPEL study
Based on results of prior trials (TAGS, REGARD, RAINBOW), it seems promising to combine Ramucirumab (Ram) beyond progression (PD) with TAS-102 (trifluridine/tipiracil). The purpose of RE-ExPEL is to investigate the tolerability, safety and benefit of Ram beyond PD in combination with TAS-102 in advanced esophagogastric adenocarcinoma (EGA).
This is a multicenter, non-randomized, open-label investigator initiated pilot trial. 20 ram-pretreated patients (pts) with advanced EGA were enrolled to a maximum of 4 cycles of ramucirumab 8mg/kg every two weeks (days 1, 15; qd28) plus TAS-102 35 mg/m2 /p.o. bid (d1-5 and d8-12; qd28). Primary endpoint (EP) was tolerability and toxicity, defining a positive trial if SAE rate according (acc.) to CTCAE 5.0 will increase less than 30% (up to 55%) compared with results from TAGS (SAE-rate 43%). Secondary EPs are further safety data and efficacy data, OS, PFS and ORR.
20 pts (20% female) were enrolled between Oct 2020 and Aug 2021, 20% gastric and 80% GEJ- cancers, 55% of pts with ECOG 0. Results of the final analysis showed that only 25% of pts had at least one SAE and the total no. of SAEs was 9, one with fatal outcome, all without relationship to systemic therapy and no SUSAR reported. RE-ExPEL was able to show a median OS of 9.1 mo (95% CI 5.4;10.1), a PFS of 2.9 mo (1.7;4.8) and a DCR of 45%. 90% of pts got study medication in 3rd line whereas 10% were even further line pts.
The safety data showed a favorable safety profile with a low rate of severe toxicity for ram+TAS-102, maybe due to the long disease stabilization and therefore less tumor associated symptoms. Regarding the primary safety endpoint, the trial was positive with even a numerically lower SAE rate compared with TAGS. Furthermore, RE-ExPEL was able to show very promising efficacy data for the combination ram plus TAS-102 with a median OS of 9.1 mo. Ram+TAS-102 seems to be more effective than TAS-102 alone acc. to TAGS-trial respecting the limitation of the RE-ExPEL one arm study design with only 20pts. The combination needs further evaluation in a randomized phase III trial.
EudraCT-No.: 2020-001075-32.
Institut für Klinische Krebsforschung IKF GmbH.
Pharmaceutical Company: Lilly.
A. Stein: Honoraria (Institution): Servier, Lilly; Research grant / Funding (institution): Servier. S. Al-Batran: Advisory / Consultancy: Bristol-Myers Squibb, Immutep, Lilly; MacroGenics; MSD Sharp & Dohme; Speaker Bureau / Expert testimony: AIO Studien gGmbH, Bristol-Myers Squibb, Lilly; MCI Deutschland GmbH; Research grant / Funding (institution): AstraZeneca; German Research Foundation; Hospira; Immutep; Roche, Bristol-Myers Squibb; German Cancer Aid (Krebshilfe); Ipsen; Lilly; MEDAC, Celgene; Eurozyto; Federal Ministry of Education and Research; MSD Sharp & Dohme; Sanofi; Vifor; Officer / Board of Directors: Institute of Clinical Cancer Research IKF at Northwest Hospital. All other authors have declared no conflicts of interest.
