Irinotecan Drug-Eluting Beads Improve Outcomes in Colorectal Cancer Patients With Liver Metastases


Key Points

  • In a randomized controlled trial of patients with unresectable colorectal cancer and liver metastases, irinotecan drug-eluting beads given with FOLFOX and bevacizumab improved response rates.
  • Hepatic progression-free survival was also improved, as was the ability to downsize tumors for resection.

Irinotecan drug-eluting beads given simultaneously with FOLFOX (leucovorin, fluorouracil, oxaliplatin) and bevacizumab (Avastin) in patients with unresectable liver metastasis from colorectal cancer improved response rates, increased resectability and prolonged hepatic progression-free survival in a study reported by Robert C. Martin, MD, of the University of Louisville in Kentucky, at the 2014 Gastrointestinal Cancers Symposium in San Francisco (Abstract 174).

“Reports have demonstrated the activity of combining both irinotecan and oxaliplatin into a FOLFOXIRI [FOLFOX/irinotecan] therapy. An option to gain similar benefits and less toxicity would be to administer the irinotecan through a hepatic arterial approach. The aim of this study was to assess the maximal response and adverse event rates of irinotecan drug-eluting beads (DEBIRI) with FOLFOX and bevacizumab as a first-line treatment for unresectable colorectal liver metastasis,” Dr. Martin explained.

The drug-eluting beads are a proprietary product that contains 100-mg irinotecan in the form of 100- to 300-micron beads administered via infusion into the hepatic artery.

Study Methods

The study included 70 patients with metachronous and synchronous liver metastases from colorectal cancer who were randomly assigned to modified FOLFOX6 plus bevacizumab (n = 30) or modified FOLFOX6, bevacizumab and DEBIRI (FOLFOXDEBIRI) (n = 40).

FOLFOX/bevacizumab and the drug-eluting beads were generally administered on alternate weeks. All 40 patients in the experimental arm received one infusion of DEBIRI, 37 received two, 18 received three, 13 received four, 4 received five, and 3 received six infusions. 

The primary endpoints were response rates and adverse events. Secondary endpoints were conversion to resection and progression-free survival. Patients received a median number of eight chemotherapy cycles (with no differences between the arms).

High Response Rates

The overall response rate was significantly higher with FOLFOXDEBIRI than with FOLFOX/bevacizumab. By modified RECIST criteria, responses were observed in 79% vs 54%, respectively, at 2 months, 91% vs 59% at 4 months, 83% vs 64% at 6 months, 54% vs 27% at 9 months, and 50% vs 24% at 12 months. These differences were statistically significant; however, differences in response by standard RECIST 1.1 criteria were not.

Dr. Martin explained that standard RECIST 1.1 assessment depends upon the diameter of the tumor, while modified RECIST does not rely on this.

“The challenge with using any hepatic arterial therapy is that the diameter of liver tumors doesn’t change much, but you do see tumors go from hypervascular to partially vascular,” he said in an interview with The ASCO Post. “So by standard RECIST, we don’t see much tumor change (ie, response), but we see stable disease. By modified RECIST, we showed a statistically significant improvement in both overall response and target response.”

With FOLFOXDEBIRI, significantly more patients were downsized to resectability (35% vs 16%; P = .05), and in this group median progression-free survival was improved, from 7.6 months in the control arm to 15.3 months, with FOLFOXDEBIRI.

“The enhanced response rate led to great downsizing to resection and subsequent improvement in hepatic progression-free survival,” Dr. Martin noted.

Overall progression-free survival, however, was not improved in the experimental arm, whose median progression-free survival was 12 months, compared with 15 months with FOLFOX alone (P = .18).

Dr. Martin said due to the size of the study and limited follow-up, statistically significant differences in these endpoints would not be expected.

Adverse Events

“Simultaneous modified FOLFOX6 with bevacizumab and hepatic arterial irinotecan drug-eluting beads is safe, without causing chemotherapy delivery delays and without increasing chemotherapy toxicity,” Dr. Martin said.

There were 144 grade 3 to 4 adverse events in 32 patients on the DEBIRI arm and 36 among 18 patients in the control arm. Serious adverse events numbered 57 and 15, respectively, which was significantly higher for the DEBIRI arm (P = .03). Chemotherapy-related adverse events numbered 38 and 21, respectively (P = .08).

“Simultaneous FOLFOXDEBIRI leads to improved overall response rates, improved hepatic progression-free survival [not statistically significant], and more durable overall progression-free survival in patients in patients downsized to resection,” Dr. Martin concluded.

He suggested that the “keys to effectiveness and expansion” will be to define patients with liver-dominant disease, to maintain proper DEBIRI techniques and dosing, to collaborate with medical oncologists, and to follow an appropriate treatment strategy that follows up in the reevaluation for surgical resection.

Dr. Martin reported a consultant or advisory role with Biocompatibles International.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.