Regorafenib (REG) is an oral multikinase inhibitor with survival benefit in salvage line therapy for metastatic colorectal cancer (mCRC); fatigue and malaise which are common adverse events (AEs) cause REG treatment discontinuation. Oral steroids are empirically used for treatment of cancer related fatigue, although there is only a few evidence. KSCC1402/HGCSG1402 is a phase II, randomized, double-blind, placebo-controlled study evaluating the prophylactic effects of oral dex on REG-related fatigue and malaise for pts with mCRC.
Eligibility included mCRC, objective failure of standard therapy, ECOG performance status 0 or 1. ≤Grade 1 fatigue or malaise was allowed to be enrolled in this study. Pts were 1:1 randomly assigned to an oral steroids group (dex 2 mg/day, 4 weeks) or a placebo (PLC) group with REG (160 mg/day, 3 weeks on/1 week off). The protocol period was scheduled for first 28 days of REG treatment. The primary endpoint was incidence of fatigue or malaise (CTCAE ver. 4, all grades) during the protocol period. Secondary endpoints included patient-reported outcome (PRO) (CTCAE and the Brief Fatigue Inventory), AEs, relative dose intensity of REG. Response, progression free survival and overall survival were also evaluated as exploratory endpoints.
Between October 2014 and December 2015, 74 pts were enrolled and randomized (dex: 37, PLC: 37). Baseline characteristics were balanced between the two arms. The incidence of all grade of malaise and/or fatigue based on CTCAE for dex group was 55.6% and 58.3% for PLC group (p = 0.8119), that based on PRO CTCAE for dex was 47.2% and 58.3% for PLC (p = 0.3450). The incidence of ≥ grade 2 of malaise and/or fatigue based on CTCAE for dex group was 19.4% and 38.9% for PLC group (p = 0.0695), that based on PRO for dex was 27.8% and 52.8% for PLC (p = 0.0306). The most common AE during protocol period was hand foot skin reaction in both groups (75.0 % vs. 86.1%).
The KSCC1402/HGCSG1402 study provided promising results that improve the supportive therapy for pts with REG-related fatigue and malaise. (NCT02288078)
Clinical trial identification
UMIN000015131 Release date: 2014/09/11; NCT02288078 Release date: 2014/10/28
Legal entity responsible for the study
Clinical Research Support Center Kyushu
Bayer Yakuhin, Ltd
S. Yuki: Honoraria: Taiho Pharmaceutical, Merck Serono, Bristol-Myers Squibb, Takeda Pharmaceutical, Chugai Pharmaceutical, Bayer Yakuhin, Eli Lilly Japan. Y. Komatsu: Taiho Pharmaceutical, Yakult Honsha, Chugai Pharmaceutical, Merck Serono, Pfizer Japan, Novartis Pharma, Ono Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, Eli Lilly Japan, Novartis Pharma, Daiichi Sankyo, Kureha Corporation. E. Oki: Honoraria: Bayer Yakuhin. H. Baba: Honoraria: Bayer Yakuhin. All other authors have declared no conflicts of interest.