TAS-102 Phase III study for metastatic colorectal cancer showed improved survival -
ESMO 16th World Congress on the GI gastrointestinal cancer
The new TAS-102 combination agent is able to improve overall survival compared to placebo in patients with metastatic colorectal cancer refractory to standard treatments, the researchers said global ESMO 16 Congress gastrointestinal cancer intestinal Barcelona.
"About 50% of patients with colorectal cancer develop metastases but eventually many of them do not respond to standard treatments," said Takayuki Yoshino of the Hospital East National Cancer Center Chiba, Japan, the lead author of the Phase III trial RESORT. "The study shows that RESORT TAS-102 improves overall survival in these patients compared to placebo. I believe that this agent will become one of the standards of care in the context refractory metastatic colorectal cancer in Japan and the world."
TAS-102 is a novel anti-tumor nucleoside consists of trifluridine agent (FTD) and tipiracil hydrochloride (TPI). DFT is the active component of TAS-102 and is directly incorporated into the DNA of cancer, leading to dysfunction of DNA. However, where FTD is taken orally, it is largely degraded to an inactive form. TPI prevents the degradation of FTD. This mechanism of action is different from that fluoropyrimidine, oxaliplatin, and irinotecan.
The Phase II trial of TAS-102 had found an overall survival benefit in Japanese patients with refractory colorectal cancer metastases to fluoropyrimidine 5-fluorouracil (5-FU), irinotecan and oxaliplatin.
The current study was a RESORT global phase III trial conducted in 13 countries at 114 centers. The patients had refractory metastatic colorectal cancer to all standard therapies, including fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab and cetuximab or panitumumab in patients with KRAS wild type tumors. The patients were randomized 2: 1 to TAS-102 (534 patients) or placebo (266 patients). The primary endpoint was overall survival
The researchers found that TAS-102 prolonged overall survival compared to placebo (hazard ratio 0.68) :. Median overall survival was 7.1 months for TAS-102 and 5.3 months for the placebo group. TAS-102 also improved progression-free survival compared to placebo (hazard ratio 0.48), which was a secondary endpoint. Yoshino said. "We found a statistically significant difference in overall survival and progression-free and clinically significant improvement"
"TAS-102 has a soft safety profile and the most common side effect is hematologic toxicity including neutropenia. patients with refractory to standard therapies of metastatic colorectal cancer now have a strong treatment option. "
Commenting on these data, ESMO spokesperson Jean Yves Douillard, Professor of oncology medical Institute of Meteorology Canc-West (ICO) Ren- Gauducheau, Saint-Herblain, France, said: "the trial of TAS-102 phase III is a comprehensive study and confirms the results of the study Phase II in Japanese patients, whose response to fluoropyrimidine is slightly different from patients in Europe and the United States. It is good to know that the magnitude of the benefit shown in smaller phase II trial is confirmed in Phase III testing more and that the results are applicable to Asians and Caucasians alike. "
TAS-102 is a combination of two components. tipiracil hydrochloride (ITP) prevents degradation of trifluridine (FTD) and also has an angiogenic activity. "This is probably why TAS-102 is effective in fluoropyrimidine 5-fluorouracil classic (5-FU) resistant patients. The drug is very promising, the tolerance is good and is manageable with supportive care."
Douillard concluded "in RESORT, TAS-102 was tested in patients who received any type of chemotherapy available for colorectal cancer, I'd probably move this drug in an earlier line of treatment and I would also combine either irinotecan or oxaliplatin with .. "
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