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.
Results of the phase III TAGS study, which were presented at the 2018 ESMO Congress, showed that TAS-102 was associated with a 31% reduction in the risk of death compared with placebo in patients with heavily pretreated metastatic or advanced gastric or GEJ cancer.
The median overall survival (OS) was 5.7 months with TAS-102 versus 3.6 months for those on the placebo arm (HR, 0.69; 95% CI, 0.56-0.85; P
= .0003). Twelve-month OS rates were 21.2% versus 13.0%, for TAS-102 and placebo, respectively. The median progression-free survival (PFS) was 2.0 months for TAS-102 compared with 1.8 months for placebo (HR, 0.57; P
<.0001). Moreover, the therapy was found to have a manageable safety profile.
Patients were randomized in a 2:1 ratio to receive TAS-102 (n = 337) at 35 mg/m2 twice daily on days 1 to 5 and 8 to 12 of each 28-day cycle or placebo (n = 170). Poststudy systemic therapy was received by one-quarter of patients in each group.
TAGS was conducted to confirm findings from a phase II Japanese study in patients with metastatic gastric cancer, in which TAS-102 was evaluated after failure of standard chemotherapies or irinotecan. Results showed a median OS of 8.7 months and a disease control rate of 65.5%.
Based on these data, the FDA granted a priority review designation to a supplemental new drug application for TAS-102 in this setting in October 2018. Under the Prescription Drug User Fee Act, the FDA is scheduled to decide on the approval by February 24, 2019.
In an interview with OncLive
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.