Trifluridine/tipiracil: Benefits persist regardless of surgery for heavily pretreated gastric cancer
Whether patients had prior gastrectomy did not attenuate the survival benefit conferred by oral trifluridine/tipiracil for those with heavily pretreated metastatic gastric/gastroesophageal junction (G/GEJ) adenocarcinoma, according to new updates from the TAGS study presented at ASCO GI Cancers Symposium (GICS) 2019.
“The data from this analysis reinforce the benefit for trifluridine/tipiracil at prolonging survival versus placebo, and this is regardless of prior gastrectomy,” said Dr David Ilson of the Memorial Sloan Kettering Cancer Center in Manhattan, New York City, US.
As gastrectomy can affect the pharmacokinetics of oral therapies, it is important to understand whether this factor affects response to trifluridine/tipiracil in patients with metastatic G/GEJ cancer — of which an estimated 40 percent had gastrectomy during the course of the disease.
In a subanalysis of 221 patients who had gastrectomy in the TAGS study, patients in the trifluridine/tipiracil arm lived significantly longer than the placebo arm (median overall survival [OS], 6.0 vs 3.4 months, hazard ratio [HR], 95 percent confidence interval [CI], 0.57, 0.41–0.79). Median progression-free survival (PFS) was also longer in patients on trifluridine/tipiracil compared with placebo (2.2 vs 1.8 months, HR, 0.48, 95 percent CI, 0.35–0.65). [GICS 2019, abstract 3]
These findings were consistent with those in the overall population, which had previously been reported in the ESMO 2018 congress. The primary analysis showed that patients treated with trifluridine/tipiracil had longer OS (median, 5.7 vs 3.6 months, HR, 0.69; p=0.0006) as well as PFS (median, 2.0 vs 1.8 months, HR, 0.57, p<0.0001) compared with those who received placebo.
“Prior gastrectomy was not identified as a prognostic or predictive factor in multivariate Cox regression analyses in which all prespecified factors were included,” said Ilson. “Treatment effect size remained the same after adjusting for all identified potential prognostic factors, such as ECOG PS, age, number of prior regimens, number of metastatic sites, and HER2 status.”
Trifluridine/tipiracil has previously been approved by the US FDA for refractory metastatic colorectal cancer. The current phase III, double-blind, multicentre TAGS study involved 507 patients with metastatic G/GEJ adenocarcinoma previously treated with at least two chemotherapy regimens, of which 221 who had gastrectomy were included in the current subanalysis. The patients were randomized 2:1 to receive oral trifluridine/tipiracil or placebo, both in addition to best supportive care.
Noting that at least 40–50 percent of patients with gastric cancer had disease recurrence despite first- or second-line treatments, the investigators highlighted that effective therapies for heavily pretreated patients “are a persisting unmet medical need”.
“Trifluridine/tipiracil is an effective treatment option with a manageable safety profile for patients with metastatic gastric cancer regardless of prior gastrectomy,” said IIson.
Although haematologic adverse events such as grade ≥3 neutropenia (44 percent vs 34 percent) and grade ≥3 leukopenia (14 percent vs 9 percent) appeared to be more common among trifluridine/tipiracil-treated patients with gastrectomy than in the overall population, Ilson pointed out that “this did not result in more treatment discontinuations.”
Exposure to trifluridine/tipiracil was also similar between patients with prior gastrectomy and the overall population, he added.
“The toxicity differences do not always translate in functional impact and treatment cessation. This is only part of the picture,” said invited discussant Dr Martine Extermann of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida, US. “Quality of life and functional status add to the picture.”