Expert Highlights Promising Findings With Trifluridine/Tipiracil in Heavily Pretreated Gastric/GEJ Cancer


Ben George, MD, discusses the findings from the phase III TAGS study and how these data can impact the treatment landscape of metastatic gastric cancers.

Ben George, MD

TAS-102 (trifluridine/tipiracil; Lonsurf), also known as FTD/TPI, was recently granted a priority review by the FDA for use in pretreated patients with advanced or metastatic gastric adenocarcinoma, including cancer of the gastroesophageal junction (GEJ), based on encouraging results seen in the phase III TAGS study.

In this trial, patients were randomized to receive either FTD/TPI or placebo in a 2:1 ratio. Both the primary endpoint of this study, overall survival (OS), and secondary endpoint, progression-free survival (PFS), were met and considered statistically significant. Patients in the experimental arm also had a disease control rate of 44% compared to 14% in the placebo arm.

Patients in this trial were heavily pretreated with around 62% of patients having at least 3 prior lines of chemotherapy, including either fluoropyrimidine, platinum, taxane, or irinotecan (Camptosar). According to Ben George, MD, the results from this trial are encouraging in the third-line or as a salvage therapy.

“FTD/TPI will definitely be a very viable treatment option for patients who failed fluoropyrimidine, platinum, taxane, or irinotecan,” said George, associate professor of medicine and director of Phase I Program at the Medical College of Wisconsin.

In an interview withTargeted Oncologyat the 2018 ISGIO Annual Conference,George discussed the findings from the TAGS study and how these data can impact the treatment landscape of metastatic gastric cancers.

TARGETED ONCOLOGY:Can you provide us with the rationale for the phase III TAGS study?

George: Metastatic gastric cancer has limited treatment options and there is a huge unmet medical need in this area. We know that the 5-year survival in metastatic gastric cancer is roughly 4%. Current standard of care for patients with gastric cancer involve treatment with a fluoropyrimidine, platinum, taxane, or irinotecan, along with a few targeted agents in specific sub populations. There is clearly a need for the new drug in the salvage setting in patients who have failed standard chemotherapy agents.

TAGS is a randomized study that was launched on promising results from a phase II study, EPOC1201, that was done in Japan and evaluated the effect of FTD/TPI in patients who had failed at least 2 prior chemotherapy programs. Based on those promising results, TAGS was launched as a multicenter randomized phase III study run in about 110 centers across 17 countries.

TARGETED ONCOLOGY:What were the findings from this study?

George: The TAGS study, again, is a multicenter phase III study where patients were randomized either to FTD/TPI or placebo in a 2:1 fashion. FTD/TPI was administered at 35 mg/m2twice daily on days 1 to 5 and 8 to 12 of a 28-day cycle. Then, patients had a control arm of placebo. About 507 patients were randomized in a 2:1 fashion with a primary endpoint of OS. Patients were stratified by their ECOG performance status, region, and prior [chemotherapy] treatment. Patients continued treatment until progression, withdrawal, or intolerance to the drug.

The primary endpoint was met in a very good fashion in a sense that FTD/TPI demonstrated a clinically significantly and statistically significant improvement in OS compared to the placebo with a very strong hazard ratio of 0.69.

I think there are a few key, important things that we need to think about when we put this in context. One is that this is a very heavily pretreated population. Just about 62% of patients had at least 3 prior lines of chemotherapy. We also know that the secondary endpoints of PFS was met in a statistically significant fashion. One of the things that was looked at in the study that is unique to this is time to deterioration of ECOG performance status 2 or more. Again, FTD/TPI clearly demonstrated that the time ECOG performance status deterioration to 2 or more was meaningfully longer in the FTD/TPI arm versus the placebo arm.

One of the key findings of the TAGS study was that in a heavily pretreated patient population, a disease control rate of 44% was achieved with FTD/TPI compared to about 12% in the placebo. This is meaningful because the disease control rate encompassed both objective response rate and stable disease, somewhat impressive in a heavily pretreated population.

TARGETED ONCOLOGY:How do you see these results impacting the field?

George: I think FTD/TPI is currently awaiting priority review with the FDA based on these promising results that have been published inLancet Oncology. I do think this will become a very meaningful salvage treatment for patients who have been exposed to 2 or more lines of prior chemotherapy.

TARGETED ONCOLOGY:What advice would you give to a community oncologist treating this patient population?

George: I think it is important to think about the treatment strategy that you decide for these patients. For the most part, I would say that every patient who walks in the door with advanced or metastatic gastric cancer should have a treatment plan across lines of therapy. No matter what you decide to do in the frontline—and in this country, very often people are treated with a fluoropyrimidine and platinum, with or without a taxane in the frontline in this setting—you need to have a treatment plan lined up for your second-line and third-line patients, keeping in mind the efficacy data and survival data with frontline, second-line, and salvage treatments available.

Based on the TAGS study, FTD/TPI will definitely be a very viable treatment option for patients who failed fluoropyrimidine, platinum, taxane, or irinotecan, becoming an effective third-line treatment for these patients.


Arkenau H-T, Tabernero J, Shitara K, et al. TAGS: a phase 3, randomised, double-blind study of trifluridine/tipiracil (TAS-102) versus placebo in patients with refractory metastatic gastric cancer. Presented at: 2018 ESMO Congress; October 19-23, 2018; Munich, Germany. LBA25.

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