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

TY - JOUR

T1 - Ramucirumab beyond progression plus TAS-102 in patients with advanced or metastatic esophagogastric adenocarcinoma, after treatment failure on a ramucirumab-based therapy

AU - Goetze, Thorsten Oliver

AU - Stein, Alexander

AU - Lorenzen, Sylvie

AU - Habibzada, Timorshah

AU - Goekkurt, Eray

AU - Herhaus, Peter

AU - Loose, Maria

AU - Sookthai, Disorn

AU - Brulin, Tanita

AU - Ihrig, Kristina

AU - Pauligk, Claudia

AU - Al-Batran, Salah-Eddin

N1 - © 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

PY - 2023/11/15

Y1 - 2023/11/15

N2 - 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.

AB - 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.

KW - Humans

KW - Trifluridine/adverse effects

KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects

KW - Treatment Failure

KW - Adenocarcinoma/pathology

KW - Stomach Neoplasms/pathology

KW - Esophagogastric Junction/pathology

KW - Ramucirumab

U2 - 10.1002/ijc.34652

DO - 10.1002/ijc.34652

M3 - Short publication

C2 - 37455496

VL - 153

SP - 1726

EP - 1733

JO - INT J CANCER

JF - INT J CANCER

SN - 0020-7136

IS - 10

ER -