The combination of regorafenib (Stivarga) plus an oral fluoropyrimidine,
TAS-102, (trifluridine/tipiracil; Lonsurf), as third-line treatment in
patients with metastatic colorectal cancer (mCRC) achieved a clinically
meaningful disease control rate (DCR) in the phase I dose-escalation
trial REMETY, according to data presented at the 2020 Gastrointestinal
Of 12 patients treated at dose level 1 (n = 6) and dose level 2 (n = 6),
7 patients achieved stable disease after 8 weeks, with a DCR of 58.3%,
reported the investigative team led by Markus H. Moehler, MD, from the
University Medical Center of the Johannes Gutenberg University Mainz,
Germany, in a poster presentation at the symposium.
With >12 months of follow-up for all patients, the median overall
survival had not been reached, as only 6 events occurred. The estimated
median progression-free survival (PFS) based on the full analysis set of
12 patients was 3.81 months (95% CI, 1.51-5.29). The PFS rate at 6
months was 0.11 (95% CI, 0.0-0.3), and no PFS was observed at 12 months
after initiation of TAS plus regorafenib.
Dose level 1 was comprised of TAS-102 at 25 mg/m2 twice daily, and
regorafenib at 120 mg/day. TAS-102 was given on days 1 to 5 and 8 to 12
of 28-day cycles, and regorafenib was given on days 2 to 22. At dose
level 2, the dose of TAS was increased to 35 mg/m2 twice daily, while
the regorafenib dose remained at 120 mg/day.
One dose-limiting toxicity (DLT) was observed in 1 of the 6 patients
dosed at level 1. At dose level 2, there were 2 DLTs among 2 of the 6
patients dosed at this level. All DLTs were grade-3 hypertension, with
regorafenib determined to be the cause.
“The results indicate a recommended phase II dose of 25 mg/m2 of TAS-102
twice daily and 120 mg of regorafenib daily,” the researchers commented
in their poster.
At the recommended phase II dose, the DCR was 83.3% compared with 33.3%
at dose level 1. No remissions were observed at either dose level.
Historical data in patients with metastatic refractory CRC show a DCR of
41% with regorafenib alone2 and 44% for TAS-102 alone,3 the
“So far, the risk-benefit assessment of the combination is positive,
taking into consideration that hypertension is clinically manageable and
no additional DLT was attributed to TAS-102,” the investigations