to other commonly used regimens, according to results of a randomized, open-label, phase 3 trial.
Median progression-free survival for patients receiving the S-1–containing regimen was 14.0 months, compared with 10.8 months for patients receiving either mFOLFOX6 or CapeOX plus bevacizumab (P less than .0001 for noninferiority; P less than .0815 for superiority), Yuji Yamada, MD, of National Cancer Center Hospital, Tokyo, and coauthors reported.
Based on these results, “we consider S-1 and irinotecan plus bevacizumab to be an effective first-line therapy for mCRC and believe that it can be included as one of the recommended standard regimens,” Dr. Yamada and colleagues said (Ann Oncol. 2017 Dec 17.).
S-1, a combination preparation that includes the 5-fluorouracil prodrug tegafur plus the modulators gimeracil and oteracil potassium, has been approved in Japan and is approved by the European Medicines Agency for gastric cancer, authors wrote.
Their phase 3 trial, known as TRICOLORE, included 487 patients randomly assigned to receive S-1 and irinotecan plus bevacizumab or a control group that received an oxaliplatin-based regimen (either mFOLFOX6 or CapeOX).
Oxaliplatin-based regimens are associated with milder alopecia and gastrointestinal toxicity, compared with irinotecan-based regimens but can result in prolonged peripheral neuropathy that can negatively impact quality of life and may lead to treatment discontinuation, Dr. Yamada and associates said.
Adverse events of grade 3 or higher occurred in 58.6% of the S-1/irinotecan/bevacizumab group and 64.9% of the control group. The most common grade 3 or greater adverse events were neutropenia and diarrhea in the S-1 group, and neutropenia and peripheral sensory neuropathy in the controls.
The median 14-month progression-free survival for S-1/irinotecan/bevacizumab establishes its noninferiority to the standard regimens, according to the authors: “Although superiority could not be proven, the median progression-free survival was 3.2 months longer in the experimental group than in the control group, and the quality of life results were favorable,” they wrote.
Quality of life was not statistically different between arms as measured by the Functional Assessment of Cancer Therapy-Colorectal Trial Outcome Index, according to the report. However, scores on the FACT/Gynecologic Oncology Group-Neurotoxicity subscale showed a “significantly more favorable trend over time in the experimental group,” authors noted.
The study was supported in part by Taiho Pharmaceutical. Dr. Yamada reported receiving honoraria from Taiho, Chugai, and Yakult.
SOURCE: Yamada Y et al. Ann Oncol. 2017 Dec 17. .