Real-World Data of Trifluridine/Tipiracil for Patients With Advanced Gastric Cancer: A Multi-Institutional Retrospective Study

Background: A trial with trifluridine/tipiracil (FTD/TPI) versus placebo in patients with heavily pretreated metastatic gastric cancer showed that FTD/TPI is effective with manageable toxicity in these patients. However, real-world data on the effects of FTD/TPI in patients with advanced gastric cancer (AGC) are limited. Methods: We retrospectively collected and analyzed the clinicopathological data of patients with AGC who received FTD/TPI monotherapy at our institutions (Kobe City Medical Center General Hospital, Osaka Red Cross Hospital, Himeji Red Cross Hospital, and Kansai Medical University Hospital) between September 2019 and July 2021. Tumor responses were evaluated based on the Response Evaluation Criteria in Solid Tumors, version 1.1. Overall survival (OS) and progression-free survival were estimated using the Kaplan-Meier method. Results: A total of 53 patients were included in the study. The median age was 70 (range, 37-85) years; 39 patients (74%) were men; the numbers of patients with Eastern Cooperative Oncology Group performance status scores of 0, 1, and 2 were 10 (19%), 39 (74%), and 4 (8%), respectively; and 27 patients (51%) had diffuse-type histology. A total of 29 patients (56%) had ascites. Prior nivolumab therapy was administered to 49 patients (92%). The response rate and disease control rate (DCR) were 2% and 35%, respectively. The median progression-free survival was 2.4 months, and OS was 5.8 months. Patients with ascites exhibited significantly shorter OS (8.6 vs 4.7 months, P = .0291) than those without ascites, and DCR (54% vs 18%, P = .0055) was significantly worse in patients with ascites. There was no significant difference in the frequency of adverse events of grade 3 or higher between patients with and without ascites. Conclusion: In a real-world setting, FTD/TPI has similar effectiveness as late-line chemotherapy for patients with AGC, including those who previously had received nivolumab.

[1]  Yoon-Koo Kang,et al.  Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. , 2022, The Lancet. Oncology.

[2]  J. Ajani,et al.  First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial , 2021, The Lancet.

[3]  T. Ando,et al.  Safety and activity of trifluridine/tipiracil and ramucirumab in previously treated advanced gastric cancer: an open-label, single-arm, phase 2 trial. , 2021, The lancet. Gastroenterology & hepatology.

[4]  I. Hyodo,et al.  Retrospective analysis for the efficacy and safety of nivolumab in advanced gastric cancer patients according to ascites burden , 2020, International Journal of Clinical Oncology.

[5]  T. Yamanaka,et al.  REVIVE study: a prospective observational study in chemotherapy after nivolumab therapy for advanced gastric cancer. , 2020, Future oncology.

[6]  E. Oki,et al.  Phase Ib/II Study of Biweekly TAS‐102 in Combination with Bevacizumab for Patients with Metastatic Colorectal Cancer Refractory to Standard Therapies (BiTS Study) , 2020, The oncologist.

[7]  H. Katayama,et al.  Randomized phase II/III study of 5-fluorouracil/l-leucovorin versus 5-fluorouracil/l-leucovorin plus paclitaxel administered to patients with severe peritoneal metastases of gastric cancer (JCOG1108/WJOG7312G) , 2020, Gastric Cancer.

[8]  G. Beretta,et al.  Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. , 2018, The Lancet. Oncology.

[9]  A. Jemal,et al.  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries , 2018, CA: a cancer journal for clinicians.

[10]  Tae Won Kim,et al.  Results of a Randomized, Double-Blind, Placebo-Controlled, Phase III Trial of Trifluridine/Tipiracil (TAS-102) Monotherapy in Asian Patients With Previously Treated Metastatic Colorectal Cancer: The TERRA Study. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  K. Yamashita,et al.  Propensity Score Analysis of Regorafenib Versus Trifluridine/Tipiracil in Patients with Metastatic Colorectal Cancer Refractory to Standard Chemotherapy (REGOTAS): A Japanese Society for Cancer of the Colon and Rectum Multicenter Observational Study , 2017, The oncologist.

[12]  T. Yoshikawa,et al.  Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial , 2017, The Lancet.

[13]  J. Lee,et al.  Response rates to single-agent chemotherapy after exposure to immune checkpoint inhibitors in advanced non-small cell lung cancer. , 2017, Lung cancer.

[14]  Marc Peeters,et al.  Randomized trial of TAS-102 for refractory metastatic colorectal cancer. , 2015, The New England journal of medicine.

[15]  J. Kinoshita,et al.  Oncotargets and Therapy Dovepress , 2022 .

[16]  Masahiro Kato,et al.  Weekly Intravenous and Intraperitoneal Paclitaxel Combined with S-1 for Malignant Ascites due to Advanced Gastric Cancer , 2010, Oncology.

[17]  F. Nakagawa,et al.  A novel antimetabolite, TAS-102 retains its effect on FU-related resistant cancer cells. , 2004, International journal of molecular medicine.

[18]  H. Tajiri,et al.  Sequential methotrexate and 5-fluorouracil therapy for gastric cancer patients with peritoneal dissemination: a retrospective study , 2001, Gastric Cancer.