OS benefit for trifluridine/tipiracil in advanced gastric cancer from third-line onward

Presented by

Prof. Josep Tabernero, Vall d'Hebron Institute of Oncology, Spain

Conference

ASCO GI 2021

Trial

TAGS

In third- and later-line, treatment with TAS-102 (trifluridine/tipiracil, FTD/TPI) provided a 33% reduction in the risk of death compared with placebo in patients with heavily pretreated metastatic or advanced gastric cancer. There was also a higher numerical difference between the arms for progression-free survival (PFS) and time to deterioration to ECOG ≥2. Quality of life was consistent in the third- and later-line when compared with earlier lines.

New exploratory subgroup findings from the TAGS study (NCT02500043) were presented by Prof. Josep Tabernero (Vall d'Hebron Institute of Oncology, Spain), specifically focused on results for third- and later-line treatment with trifluridine/tipiracil [1]. The TAGS study investigated the efficacy and safety of TAS-102 (trifluridine, an antineoplastic thymidine-based nucleoside analogue, and tipiracil, a thymidine phosphorylase inhibitor) plus best supportive care (BSC) compared with placebo plus BSC in patients with metastatic gastric cancer (including adenocarcinoma of the gastroesophageal junction) that was refractory to standard treatments.

Patients were randomised in a 2:1 ratio to receive TAS-102 at a 35 mg/m² twice daily on days 1 to 5 and 8 to 12 of each 28-day cycle (n=337) or placebo (n=170). CT scans were performed every 8 weeks and quality of life (QoL) assessments every 4 weeks. Crossover to open-label TAS-102 was allowed. The primary endpoint of the TAGS study was overall survival (OS), which was already met and published [2]. Key secondary endpoints were PFS and QoL. Patient characteristics were similar in the treatment arms; the primary cancer site was gastric in 71% of patients in both arms and 44% of patients per arm had received prior gastrectomy. Approximately 37% of patients in each group had received 2 prior treatments, and about 63% had received 3 or more prior treatments, including fluoropyrimidine, platinum, irinotecan, taxanes, ramucirumab, and immunotherapy.

Results showed a superior survival benefit with FTD/TPI in patients treated in the third- and later-line, with a median OS of 6.8 months in the FTD/TPI arm versus 2.8 months in the placebo arm (HR 0.67; 95% CI 0.47-0.97; P=0.032, see Figure). There was also a higher PFS benefit in the FTD/TPI arm for third-line (HR 0.54; P=0.004) and fourth- or later-line (HR 0.57; P<0.001). Time to deterioration to ECOG ≥2 was also superior in the FTD/TPI arm for third-line (HR 0.60; P=0.005) and fourth- or later-line (HR 0.75; P=0.03). QoL was consistent in the third- and later-line with the overall population.

Figure: Median overall survival in the ITT population and 3L and 4L + subgroups [1]

In short, this exploratory subgroup analysis of the TAGS study confirms the efficacy of FTD/TPI versus placebo for third- and later-line treatment of metastatic gastric cancer.

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