Novel Oral Agent Extends Survival in Relapsed/Refractory Colorectal Cancer, Phase II Study Shows
Hopes are high that TAS-102, a novel oral nucleoside agent, will turn out to be an advance in the treatment of advanced colorectal cancer, said Howard Hochster, MD, of the Gastrointestinal Cancer Program at Yale Cancer Center, New Haven, Connecticut, speaking at the Chemotherapy Foundation Symposium XXXI.
TAS-102 combines the cytotoxic agent trifluridine with the thymidine phosphorylase inhibitor tipiracil. TAS-102 is incorporated into DNA synthesis and inhibits DNA growth in cancer cells.
“This combination gives better pharmacology than either drug alone, and the compound is active in fluorouracil-resistant tumors,” Dr. Hochster noted.
Favorable Survival Results
A phase II study showed that TAS-102 improved overall survival by a median of 3 months in 172 patients with relapsed/refractory colorectal cancer; overall survival was 9 months in those treated with TAS-102 vs 6 months in the placebo group. Patients given TAS-102 were 44% less likely to die.
Additionally, 43% of patients receiving TAS-102 achieved stable disease vs 10% for those on placebo. Subgroup analysis showed favorable survival and progression-free survival outcomes for all subgroups independent of prior therapy and KRAS status.
Toxicities were mainly hematologic. In Dr. Hochster’s opinion, these were a primarily consequence of delayed neutrophil recovery.
The drug was most effective in improving survival in patients with KRAS-mutant tumors and had less of an effect on KRAS wild-type tumors.
Ongoing Phase III Study
“TAS-102 has entered phase III international study. It will be interesting to see if the KRAS results are replicated in the larger trial,” he said.
The hazard ratios for overall survival and progression-free survival in the phase II trial of TAS-102 were comparable with those in phase III trials comparing cetuximab (Erbitux), panitumumab (Vectibix), and regorafenib (Stivarga), respectively, vs best supportive care for third-line or greater treatment for metastatic colorectal cancer, Dr. Hochster said.
“If this holds up in phase III, TAS-102 may play an important role in colorectal cancer,” he said.
The phase III RECOURSE trial is enrolling patients with metastatic colorectal cancer who have been treated with two or more prior regimens and who are are refractory to fluoropyridines, irinotecan, oxaliplatin, bevacizumab (Avastin), and anti-EGFR therapy. Recruitment is being conducted in 13 countries and 122 cancer centers. Patients are randomly assigned to TAS-102 twice daily or best supportive care, and results are expected in 2014.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
