Regorafenib/TAS-102 gives clinically meaningful DCR in Metastatic CRC

The data from the REMETY phase 1 dose escalation trial, unveiled at the Gastrointestinal Cancers Symposium 2020, reportedly shows that the combination of regorafenib (Stivarga) and oral fluoropyrimidine TAS-102 provided a clinically meaningful DCR in third line treatment of individuals suffering from metastatic colorectal cancer (CRC).

The Regorafenib/TAS-102 combination also showed toxicities that were consistent with either agent’s safety profiles. Out of the 12 trial participants that were treated dose level 1 and dose level 2, seven people attained stable disease after a period of eight weeks, showing a disease control rate of 58.3%.

The investigative team was helmed by Dr Markus H. Moehler, MD, University Medical Center of Johannes Gutenberg University Mainz, Germany.

With more than 12 months of follow up of all participating patients, only six events occurred, and the median overall survival was not reached. The estimated PFS (progression-free survival), based upon the complete analysis of the 12 patients was approximately 3.81 months. At six months, the PFS rate was 0.11, and at 12 months, no PFA was seen after the initiation of regorafenib and TAS.

In one of the six patients that were given doses at level 1, one DLT (dose-limiting toxicity) was observed. Two DLTs were observed in two of the six patients at dose level 2. All the observed DTLs were found to be grade-3 hypertension caused by regorafenib.

During the poster presentation of the trial data, researchers commented that the outcomes indicate a phase II recommended TAS-102 dose of 25 mg/m2 twice daily as well as regorafenib dose of 120 mg daily.

The investigators further added that up until now, the Regorafenib/TAS-102 risk benefit assessment has been positive, considering that the grade-3 hypertension is manageable clinically and that no additional DLT was tracked back to TAS-102.

Overall, 152 adverse events were encountered, however, only five of them were considered serious. Hypertension, decreased neutrophil count, fatigue, diarrhea and nausea were the most common adverse events. 

Source credit: https://www.onclive.com/conference-coverage/gi-2020/regorafenibtas102-induces-clinically-meaningful-dcr-in-refractory-metastatic-crc