Ramucirumab beyond progression plus TAS‐102 in patients with advanced or metastatic esophagogastric adenocarcinoma, after treatment failure on a ramucirumab‐based therapy

Abstract

Based on results of prior trials (TAGS, REGARD, RAINBOW), the combination of ramucirumab beyond progression with TAS‐102 (trifluridine/tipiracil) seems to be promising in advanced esophagogastric adenocarcinoma (EGA). In this multicenter, non‐randomized, open‐label, investigator‐initiated pilot trial, ramucirumab‐pretreated patients with metastatic EGA received a maximum of 4 cycles of ramucirumab (8 mg/kg i.v. on day 1 and 15, Q2W) plus TAS‐102 (35 mg/m2 p.o. bid on day 1‐5 and day 8‐12; Q2W). Primary endpoint was tolerability and toxicity, defining a positive trial if the SAE rate according to CTCAE 5.0 will increase <30% (up to 55%) compared to historical results from TAGS trial (SAE rate 43%). Secondary endpoints were further evaluation of safety and assessment of efficacy according to tumor response and overall and progression‐free survival (OS/PFS). Twenty patients, 20% gastric and 80% GEJ cancers and 55% with ECOG 0 were enrolled. In total, nine SAEs were reported in 25% [95% CI: 8.7‐49.1] of the patients, all without relationship to the systemic therapy. The median OS and PFS were 9.1 months [5.4‐10.1] and 2.9 months [1.7‐4.8], respectively. In addition, a disease control rate of 45% was obtained. The trial showed a favorable safety profile with a numerically lower incidence of SAEs for the combination of ramucirumab with TAS‐102 compared to historical TAGS trial. Furthermore, the combination demonstrated efficacy in the beyond progression setting and therefore warrants further evaluation in a randomized trial compared to TAS‐102 alone.

Trifluridine/tipiracil with and without ramucirumab for advanced gastric cancer: a comparative observational study

“…The outcomes of the FTD/TPI monotherapy group (DCR, 38.3%; median OS, 5.0 months) are consistent with those reported in the phase III TAGS trial, suggesting that our cohort is representative of the broader patient population with AGC receiving this treatment (DCR, 44%; median OS, 5.7 months) 5 . Moreover, the addition of ramucirumab in our study (ORR, 25.8%; median PFS, 2.9 months) showed a pattern of clinical benefit comparable with that observed in earlier phase II trials and retrospective studies (ORR, 0–16%; median PFS, 2.9–5.3 months) 10 , 11 , 21 . Despite these improvements in ORR and PFS, we did not observe a corresponding increase in OS.…”

“…Ramucirumab, an anti-VEGF-receptor 2 monoclonal antibody, is an established standard of care for AGC, as evidenced by the results of the REGARD and RAINBOW trials 8 , 9 . Several single-arm phase II trials of FTD/TPI combined with ramucirumab exhibited promising antitumor activity and feasible safety profile in pretreated patients with AGC 10 , 11 .…”