Efficacy and Safety of Trifluridine/Tipiracil Treatment in Patients With Metastatic Gastric Cancer Who Had Undergone Gastrectomy

Ilson, David H.; Tabernero, Josep; Prokharau, Aliaksandr; Arkenau, Hendrik‐Tobias; Ghidini, Michele; Fujitani, Kazumasa; Cutsem, Éric Van; Thuss‐Patience, Peter; Beretta, Giordano Domenico; Mansoor, Wasat; Zhavrid, Edvard; Alsina, María; George, Ben; Catenacci, Daniel V.T.; McGuigan, Sandra; Makris, Lukas; Doi, Toshihiko; Shitara, Kohei

doi:10.1001/jamaoncol.2019.3531

Cited by 17 publications

(14 citation statements)

References 40 publications

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“…In both 3L and 4Lþ groups, gastrectomy before FTD/TPI treatment did not have Months from randomisation an impact on efficacy, which was previously shown for the whole population of the TAGS study. 14 QoL was maintained similarly in both subgroup populations analysed, and this is consistent with the population as a whole, in which any QoL deterioration that was observed was associated with deterioration of ECOG PS. 12 The safety profile of FTD/TPI was generally consistent in the two subgroups assessed in this analysis.…”

Section: Discussionsupporting

confidence: 83%

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Trifluridine/tipiracil versus placebo for third or later lines of treatment in metastatic gastric cancer: an exploratory subgroup analysis from the TAGS study

et al. 2021

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Background: Metastatic gastric cancer and cancer of the esophagogastric junction (GC/EGJ) is an aggressive disease with poor prognosis. In the TAGS study, trifluridine/tipiracil (FTD/TPI) improved overall survival (OS) compared with placebo in heavily pre-treated patients. This unplanned, exploratory subgroup analysis of the TAGS study aimed to clarify outcomes when FTD/TPI was used as third-line (3L) treatment and fourth-or later-line (4Lþ) treatment. Patients and methods: Patients were divided into a 3L group (126 and 64 in FTD/TPI and placebo arms, respectively) and 4Lþ group (211 and 106 in FTD/TPI and placebo arms, respectively). Endpoints included OS, progression-free survival (PFS), time to Eastern Cooperative Oncology Group performance status (ECOG PS) deterioration to !2, and safety. Results: Baseline characteristics were generally well balanced between FTD/TPI and placebo for 3L and 4Lþ treatment. Median OS (mOS) for FTD/TPI versus placebo was: 6.8 versus 3.2 months {hazard ratio (HR) [95% confidence interval (CI)] ¼ 0.68 (0.47-0.97), P ¼ 0.0318} in the 3L group; and 5.2 versus 3.7 months [0.73 (0.55-0.95), P ¼ 0.0192] in the 4Lþ group. Median PFS for FTD/TPI versus placebo was 3.1 versus 1.9 months [0.54 (0.38-0.77), P ¼ 0.0004] in the 3L group; and 1.9 versus 1.8 months [0.57 (0.44-0.74), P < 0.0001] in the 4Lþ group. Time to deterioration of ECOG PS to !2 for FTD/TPI versus placebo was 4.8 versus 2.0 months [HR (95% CI) ¼ 0.60 (0.42-0.86), P ¼ 0.0049] in the 3L group; and 4.0 versus 2.5 months [0.75 (0.57-0.98), P ¼ 0.0329] in the 4Lþ group. The safety of FTD/TPI was consistent in all subgroups. Conclusions: This analysis confirms the efficacy and safety of FTD/TPI in patients with GC/EGJ in third and later lines with a survival benefit that seems slightly superior in 3L treatment. When FTD/TPI is taken in 3L as recommended in the international guidelines, physicians can expect to provide patients with an mOS of 6.8 months.

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Section: Discussionsupporting

confidence: 83%

“…In both 3L and 4L+ groups, gastrectomy before FTD/TPI treatment did not have an impact on efficacy, which was previously shown for the whole population of the TAGS study. 14 …”

Section: Discussionmentioning

confidence: 99%

Trifluridine/tipiracil versus placebo for third or later lines of treatment in metastatic gastric cancer: an exploratory subgroup analysis from the TAGS study

et al. 2021

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“…The common adverse events were haematological side effects, which could be managed with routine procedures including G-CSF support, transfusions or dose reductions. As a rational concern for an oral drug for bioavailability, a post-hoc analysis for patients with gastrectomy was recently demonstrated, where the survival advantage in the trifluridine and tipiracil arm remained significant [39]. Quality of life data also indicates an improvement of cancer-related symptoms within the trifluridine/tipiracil group [40].…”

Section: Third and Further Linesmentioning

confidence: 99%

New Treatment Options for Advanced Gastroesophageal Tumours: Mature for the Current Practice?

Puhr

Preusser

Prager

2020

Cancers

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Several clinical trials attempted to identify novel treatment options for advanced gastroesophageal tumours in first, second and further lines. Although results of targeted therapy regimens were mainly disappointing, novel immunotherapy agents showed promising activity, which led to their approval in second and third lines in many countries. This review focuses on the results of recent clinical trials investigating novel agents including targeted therapies, immunotherapy components and chemotherapies and discuss their current impact as well as current approval status on the treatment armamentarium of advanced gastroesophageal tumours.

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“…Result of this subgroup analysis indicates that treatment of patients with trifluridine/tipiracil was similarly tolerable in both subgroups, and the efficacy benefits may be greater in patients of the gastrectomy subgroup than the no gastrectomy subgroup. 14 The health-related quality of life (QoL) outcomes in the TAGS trial were analyzed and compared among patients treated with trifluridine/tipiracil and compared with placebo. Using the EORTC QLQ-30 and EORTC QLQ-ST022 questionnaires, QoL was evaluated at baseline and at each treatment cycle.…”

Section: Preclinical and Clinical Studies Using Trifluridine And Tipiracilmentioning

confidence: 99%

<p>Clinical Evaluation of the Safety and Efficacy of Trifluridine/Tipiracil in the Treatment of Advanced Gastric/Gastroesophageal Junction Adenocarcinoma: Evidence to Date</p>

Wheelden¹,

Yee²

2020

OTT

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Trifluridine/tipiracil or TAS-102 (Taiho Oncology, Lonsurf ® , Princeton, NJ, USA) is a combination tablet of trifluridine, a thymidine-based nucleoside analog, and tipiracil, a thymidine phosphorylase inhibitor, in a 1:0.5 molar ratio. This drug was first approved for use in metastatic colorectal cancer patients. Recently, the U S Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have granted approval of trifluridine/tipiracil for treatment of metastatic gastric and gastroesophageal junction adenocarcinoma in patients following at least two lines of chemotherapy including fluoropyrimidine and platinum chemotherapy agents, as well as taxanes or irinotecan. This approval was granted after the findings from first a Phase II trial (EPOC1201) investigating trifluridine/tipiracil, and later a global Phase III trial (TAGS trial) that compared trifluridine/tipiracil vs placebo with best supportive care. Both trials primarily utilized trifluridine/tipiracil at a dose of 35 mg/m 2 twice daily. In the EPOC1201 trial, the primary end point of disease control rate was greater than 50% after eight weeks of therapy. The most common grade three or four adverse event was neutropenia; additional toxicities included leukopenia, anemia, and anorexia. In the TAGS trial, overall survival in patients treated with trifluridine/tipiracil (5.7 months) was significantly improved as compared to the placebo-controlled group (3.6 months). Treatment with trifluridine/tipiracil not only did not impair quality of life but also tended to reduce the risk of deterioration of quality of life. The results of these studies along with the subsequent FDA and EMA approval have generated an important breakthrough in regard to treatment options for patients with refractory metastatic gastric or gastroesophageal junction adenocarcinoma.

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Efficacy and Safety of Trifluridine/Tipiracil Treatment in Patients With Metastatic Gastric Cancer Who Had Undergone Gastrectomy

Cited by 17 publications

References 40 publications

Trifluridine/tipiracil versus placebo for third or later lines of treatment in metastatic gastric cancer: an exploratory subgroup analysis from the TAGS study

Trifluridine/tipiracil versus placebo for third or later lines of treatment in metastatic gastric cancer: an exploratory subgroup analysis from the TAGS study

New Treatment Options for Advanced Gastroesophageal Tumours: Mature for the Current Practice?

<p>Clinical Evaluation of the Safety and Efficacy of Trifluridine/Tipiracil in the Treatment of Advanced Gastric/Gastroesophageal Junction Adenocarcinoma: Evidence to Date</p>

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