Efficacy and safety of trifluridine/tipiracil plus ramucirumab in comparison with trifluridine/tipiracil monotherapy for patients with advanced gastric cancer-single institutional experience

Mashiro Okunaka; Akihito Kawazoe; Hitomi Nakamura; Daisuke Kotani; Saori Mishima; Yasutoshi Kuboki; Yoshiaki Nakamura; Kohei Shitara

doi:10.1007/s10120-023-01427-9

Efficacy and safety of trifluridine/tipiracil plus ramucirumab in comparison with trifluridine/tipiracil monotherapy for patients with advanced gastric cancer-single institutional experience

Gastric Cancer. 2023 Nov;26(6):1030-1039. doi: 10.1007/s10120-023-01427-9. Epub 2023 Sep 4.

Authors

Mashiro Okunaka¹, Akihito Kawazoe², Hitomi Nakamura¹, Daisuke Kotani³, Saori Mishima³, Yasutoshi Kuboki³, Yoshiaki Nakamura³, Kohei Shitara³

Affiliations

¹ Department of Pharmacy, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
² Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. akawazoe@east.ncc.go.jp.
³ Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.

PMID: 37665515
DOI: 10.1007/s10120-023-01427-9

Abstract

Background: Trifluridine/tipiracil plus VEGF inhibition with ramucirumab (RAM) for advanced gastric cancer (AGC) demonstrated clinical activity with an acceptable toxicity profile in previous phase II trial. However, little is known about its efficacy and safety in clinical practice in comparison with trifluridine/tipiracil monotherapy.

Methods: We retrospectively investigated efficacy and safety of trifluridine/tipiracil plus RAM and trifluridine/tipiracil monotherapy as third or later line treatment for AGC patients.

Results: Forty-one patients receiving trifluridine/tipiracil plus RAM and 60 patients receiving trifluridine/tipiracil monotherapy were analyzed. The objective response rate (ORR) and the disease control rate (DCR) were 13.5% and 64.9% in the trifluridine/tipiracil plus RAM group, and 3.8% and 42.3% in the trifluridine/tipiracil monotherapy group, respectively (ORR; P = 0.122, DCR; P = 0.052). The median progression-free survival (PFS) and the median overall survival (OS) were 3.0 months and 7.2 months in the trifluridine/tipiracil plus RAM group, and 1.8 months and 3.8 months in the trifluridine/tipiracil monotherapy group, respectively (HR for PFS = 0.66; P = 0.059, HR for OS = 0.50; P = 0.007). Multivariate analysis showed significantly longer PFS (HR = 0.52; P = 0.011) and OS (HR = 0.51; P = 0.031) in the trifluridine/tipiracil plus RAM group compared to the trifluridine/tipiracil monotherapy group. No unexpected adverse events were observed in both groups.

Conclusions: Trifluridine/tipiracil plus RAM might show favorable anti-tumor activity with an acceptable toxicity profile in comparison with trifluridine/tipiracil monotherapy, suggesting one treatment option for AGC patients in salvage line. The combination needs further evaluation in ongoing randomized trials.

Keywords: Advanced gastric cancer; Trifluridine/tipiracil monotherapy; Trifluridine/tipiracil plus ramucirumab.

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / adverse effects
Colorectal Neoplasms*
Drug Combinations
Humans
Ramucirumab
Retrospective Studies
Stomach Neoplasms* / drug therapy
Stomach Neoplasms* / pathology
Trifluridine / adverse effects
Uracil / therapeutic use

Substances

tipiracil
Uracil
Trifluridine
Drug Combinations