Simultaneous FOLFOX/DEBIRI Leads to Resectability for Unresectable Colorectal Liver Metastases

By Robert Martin, MD, PhD

At the 2014 Gastrointestinal Cancers Symposium of the American Society of Clinical Oncology, I presented “Randomized Controlled Trial of Irinotecan Drug-Eluting Beads With Simultaneous FOLFOX and Bevacizumab for Patients With Unresectable Colorectal Liver-Limited Metastasis,” IDE submission #G080230-S001, which evaluated a randomized phase 2 study of irinotecan drug-eluting beads (DEBIRI) combined with biweekly oxaliplatin (FOLFOX) and bevacizumab that facilitated first-line conversion to liver resectability in a number of patients.

Sixty patients were randomized, half of whom received DEBIRI on off weeks and systemic FOLFOX and bevacizumab for 5 consecutive weeks, followed by biweekly doses until 22 weeks. The remainder was given FOLFOX. All patients had liver-dominant disease (defined as >80% of all metastatic tumor was within the liver) and were deemed unresectable by an HPB surgeon at outset. The primary endpoint was best overall response as defined by modified RECIST criteria and showed a significant improvement at 2, 4, and 6 month intervals (78% vs 54% at 2 months; 76% vs 60% at 6 months).

Fourteen in the multicenter (9 centers) study went on to resectability, compared to 5 in the control arm. Hepatic-specific progression-free survival (PFS) was 12.8 months (DEB) vs 10.5 months (control). We have been able to demonstrate that simultaneous FOLFOX/DEBIRI leads to improved overall response rates, improved hepatic PFS, and more durable overall PFS in patients downsized to resection. Other key findings where that there was no difference in chemotherapy related toxicity between the two arms of the study.

The main goal and downstream effects of the study will be to enhance the downsizing effects with combination therapy and allow more patients to get to surgical resection.

Editor’s note: Robert Martin, MD, PhD, is Sam and Lolita Weakley Endowed Chair in Surgical Oncology at the University of Louisville, Kentucky, and is a member of the Interventional Oncology 360 editorial board.