November 07, 2019
4 min read

Trifluridine and tipiracil safe, effective for pretreated metastatic gastric cancer regardless of prior gastrectomy

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David H. Ilson, MD PhD
David H. Ilson

Trifluridine and tipiracil significantly extended PFS and OS compared with placebo among patients with previously treated metastatic gastric or gastroesophageal junction cancer, according to results of a subgroup analysis of the randomized phase 3 TAS-102 Gastric Study.

The oral nucleoside antitumor agent trifluridine and tipiracil (Lonsurf, Taiho Oncology) — also called TAS-102 — demonstrated safety and efficacy regardless of whether patients had undergone gastrectomy.

“This is an important observation, as TAS-102 is an oral agent potentially influenced by drug absorption and is potentially effective in patients with prior gastrectomy,” David H. Ilson, MD, PhD, medical oncologist at Memorial Sloan Kettering Cancer Center and a HemOnc Today Editorial Board Member, told HemOnc Today. “This follow-up analysis from the pivotal [TAS-102 Gastric Study] indicated that PFS and OS benefits were maintained in patients who had undergone prior gastrectomy — no differences were observed in toxicity or drug delivery.”

Third- and later-line therapy for metastatic gastric cancer, which eventually becomes refractory to chemotherapy, remains an unmet need. Results of previous studies showed trifluridine and tipiracil — which combines the thymidine analogue trifluridine with the thymidine phosphorylase inhibitor tipiracil — extended PFS and OS as late-line therapy compared with supportive care only. However, the agent’s activity among the subpopulation of patients who have undergone gastrectomy had not been determined.

The placebo-controlled TAS-102 Gastric Study enrolled 507 patients (mean age, 62.5 years; 72.8% men) with pretreated metastatic gastric cancer or gastroesophageal junction cancer between Feb. 24, 2016, and Jan. 5, 2018. Patients had an ECOG performance status of 0 or 1, received at least two prior chemotherapy regimens and were refractory to or unable to tolerate the most recent therapy.

The researchers randomly assigned patients 2:1 to oral trifluridine and tipiracil dosed at 35 mg/m² twice daily (n = 337) or placebo twice daily and best supportive care (n = 170) on days 1 through 5 and 8 through 12 of 28-day treatment cycles.

Ilson and colleagues conducted a preplanned subgroup analysis of patients who underwent gastrectomy (n = 221) or had not undergone gastrectomy (n = 286).

OS served as the primary endpoint. Secondary endpoints included efficacy and safety.

Among patients who underwent gastrectomy, those who received trifluridine and tipiracil (n = 147) had longer PFS (median, 2.2 months vs. 1.8 months; HR = 0.48; 95% CI, 0.35-0.65) and OS (median, 6 months vs. 3.4 months; HR = 0.57; 95% CI, 0.41-0.79) than those who received placebo (n = 74).


Among those who had not undergone gastrectomy, researchers also observed slightly longer PFS (median, 1.9 months vs. 1.8 months; HR = 0.65; 95% CI, 0.49-0.85) and longer OS (median, 5.6 months vs. 3.8 months; HR = 0.8; 95% CI, 0.6-1.06) with trifluridine and tipiracil (n = 190) vs. placebo (n = 96).

An analysis of median time to deterioration of ECOG performance status to 2 or higher in the study treatment vs. placebo groups showed HRs of 0.63 (95% CI, 0.46-0.87) for those who underwent gastrectomy and 0.74 (95% CI, 0.56-0.98) for those who did not.

Grade 3 or higher any-cause adverse events occurred more frequently among patients treated with trifluridine and tipiracil who underwent gastrectomy vs. no gastrectomy (84.1% vs. 76.3%). Patients in the gastrectomy subgroup appeared more likely to experience grade 3 or higher events such as neutropenia (44.1% vs. 26.3%), anemia (21.4% vs. 17.4%) and leukopenia (14.5% vs. 5.3%). However, patients who did not undergo gastrectomy were more likely to experience grade 3 or higher fatigue (10.5% vs. 2.1%).

Adverse events led to dosing modifications for 94 patients (64.8%) in the gastrectomy subgroup and 101 patients (53.2%) in the no-gastrectomy subgroup. A larger percentage of patients in the no-gastrectomy subgroup discontinued treatment due to adverse events (14.7% vs. 10.3%).

The subgroup analysis lacked power for statistical significance, which served as the study’s primary limitation.

“Given the activity of [trifluridine and tipiracil] in late-line treatment, the potential to move this drug up to earlier lines of therapy in combination with other agents or other early-line agents is now considered,” Ilson told HemOnc Today. – by Jennifer Southall

For more information:

David Ilson, MD, PhD, can be reached at Memorial Sloan Kettering Cancer Center, 300 E. 66th St., BAIC 1031, New York, NY 10065; email:

Disclosures: Ilson reports grants and advisory role support from Amgen, Astellas, AstraZeneca, Bayer AG, Bristol-Myers Squibb, Eli Lilly & Co., Merck, F. Hoffman-LaRoche, Pieris Pharmaceuticals and Taiho Oncology outside of the submitted work. Please see the study for all other authors’ relevant financial disclosures.