BARCELONA-A chemotherapy combination consisting of trifluridine with tipiracil showed a "clinically meaningful and statistically significant" improvement in overall survival and progression-free survival (PFS) compared with placebo in patients with heavily pretreated metastatic gastric cancer (mGC) refractory to standard therapies in the randomized phase III TAGS study reported at the ESMO World Congress on Gastrointestinal Cancer 2018 (Abstract LBA-002).
"The TAGS study has shown in a randomized phase III setting that trifluridine-tipiracil is an available option for treating patients with gastric or gastroesophageal cancer in the metastatic refractory setting," said lead author Josep Tabernero, MD, PhD, Chair of Medical Oncology at Vall d'Hebron University Hospital in Barcelona, Spain.
Research Details
Study results show that patients lived a median of 5.7 months when treated with the new combination compared with 3.6 months in the control group receiving best supportive care-a 2.1 months extension of life and a 31-percent reduction in the risk of death (HR=0.69).
The researchers found that the safety profile was "predictable and manageable" with "no new safety signals" and concluded that the combination represented an effective treatment option for patients with heavily pretreated mGC.
The TAGS study randomized 507 patients with mGC (including gastroesophageal junction cancer) who had at least two prior regimens, including fluoropyrimidine, platinum, taxane, irinotecan, or a HER2 inhibitor. The 170 patients in the control group were given a placebo plus best supportive care, while the experimental arm of 337 patients (randomized 2-to-1) were treated with a combination of the novel oral thymidine analog trifluridine together with the thymidine phosphorylase inhibitor tipiracil and best supportive care.
"The study met the primary endpoint of increasing overall survival. Patients also benefit in long-term survival-in 1 year, for example," said Tabernero. The study also observed an advantage in PFS that was statistically significant. "There were no differences in safety profile between the two arms in the number of patients who had to discontinue treatment because of treatment-emergent adverse events," he noted. The safety profile in gastric cancer was found to coincide with documented toxicities in patients with metastatic colorectal cancer treated with trifluridine plus tipiracil.
Discussion Points
Tabernero told Oncology Times the data were clinically promising, "especially for this highly unmet need population" and that he hoped trifluridine with tipiracil would be approved by regulatory authorities for gastric cancer as it had already been "in more than 50 countries" for metastatic colorectal cancer.
Commenting on the study findings David Cunningham, MD, FRCP, Consultant Medical Oncologist and Director of Clinical Research at the Royal Marsden Hospital in London, said the significant survival advantage among patients treated with the new combination was interesting and that it was another option.
"When patients have gone through the standard treatment options-usually including 5-FU, a platinum drug, and a taxane-and they have progressed, we can think about offering them the possibility of trifluridine and tipiracil," he explained.
However, for clinical practice, Cunningham recommended that patients be assessed before receiving such treatment, especially as some were not likely to be fit for further therapy after failing three lines of treatment.
"We need to be clear about this. This won't be for everybody. But for those patients who are still fit, have good organ function, and wish to explore the possibility of further treatment these drugs represent a genuine alternative," he said.
Cunningham concluded that trifluridine with tipiracil had emerged as an option for patients who had failed standard chemotherapy. "Other options include the checkpoint antibodies like nivolumab. But this represents a regimen that can help some patients."
Peter M. Goodwin and Sarah Maxwell are contributing writers.
Learn About More Conferences
Start looking ahead to 2019 hematology/oncology conferences by visiting the Oncology Times online conference listing at http://bit.ly/1B38kF4. Here you will find dates, locations, and links for more information.