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Regorafenib Plus TAS-102 Clinically Meaningful Disease Control in mCRC

Date : 2/9/2020 / Visit Count : 988
Regorafenib Plus TAS-102 Clinically Meaningful Disease Control in mCRC

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 Cancers Symposium.

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 investigators noted.

“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 concluded.

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