Hendrik-Tobias Arkenau, MD, PhD
Although gastric and gastroesophageal junction (GEJ) cancers are heterogeneous diseases with a number of FDA-approved regimens, TAS-102 (trifluridine/tipiracil; Lonsurf) may have a place in the management of previously treated patients, according to Hendrik-Tobias Arkenau, MD, PhD.
at the 2018 ESMO Congress, Arkenau, founding medical director, executive medical director, Sarah Cannon Research Institute United Kingdom, discussed TAS-102 and how the therapy could potentially impact patients with gastric cancer.
OncLive: Please provide some background to TAS-102 and the TAGS trial.
: Gastric cancer is one of the most common cancers worldwide. One-fifth of cancer deaths that occur every year come from gastric cancer. There is very good clinical evidence that TAS-102 works very well in [patients with] colorectal cancer. It was recently proven in phase II and III trials, so there was rationale to test this on patients who failed standard-of-care therapy.
What were the findings presented at the 2018 ESMO Congress?
TAS-102 combined with best supportive care was shown to be superior in terms of OS compared with best supportive care and placebo. There was a 2-month advantage in OS, and these were patients who sometimes failed on 2 or 3 prior lines of therapy. PFS was also superior with the addition of TAS-102.
Patients who received the drug had more stable disease and a longer duration of response. Importantly, TAS-102 had a better time to disease deterioration. The drug was very well tolerated.
If approved by the FDA, how do you see this drug fitting into the landscape?
Gastric cancer is a moving field at the moment. We now have 2 FDA-approved immunotherapies in the third-line setting, but not all patients can receive these drugs. TAS-102 would be a very valid drug for the third-line setting and beyond. After frontline and second-line chemotherapy regimens, TAS-102 will find its place. It has shown meaningful PFS.
What is the impact of immunotherapy in this space?
Nivolumab (Opdivo) and pembrolizumab (Keytruda) are FDA approved for third-line treatment. However, not all patients benefit from these agents or are eligible for this type of treatment. Right now, in terms of biomarkers, PD-L1 seems to be an effective biomarker. At the same time, there are PD-L1–negative patients who benefit. Microsatellite instability high and mismatch repair deficiency are also biomarkers for immunotherapy.
What is the biggest unmet need in gastric cancer?
We have such a short window to treat these patients. We need to detect the disease much earlier for these patients. More aggressive, upfront treatment with curative intent can also help us. Gastric cancer is so complex because it is a very heterogeneous disease.
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. In: Proceedings from the 2018 ESMO Congress; October 19-23, 2018; Munich, Germany. Abstract LBA25.
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