Intra-arterial hepatic beads loaded with irinotecan (DEBIRI) with mFOLFOX6 in unresectable liver metastases from colorectal cancer: a Phase 2 study

Abstract

Background Chemo-embolisation with drug-eluting beads loaded with irinotecan (DEBIRI) increased survival as compared with intravenous irinotecan in chemorefractory patients with liver-dominant metastases from colorectal cancer (LMCRC). First-line DEBIRI with systemic chemotherapy may increase survival and secondary resection. Methods In the FFCD-1201 single-arm Phase 2 study, patients with untreated, non-resectable LMCRC received DEBIRI plus mFOLFOX6. Four courses of DEBIRI were performed alternating right and left lobe or two sessions with both lobes treated during the same session. Results Fifty-seven patients were enrolled. Grade 3–5 toxicities were more frequent when both lobes were treated during the same session (90.5% versus 52.8%). Nine-month PFS rate was 53.6% (95% CI, 41.8–65.1%). The objective response rate (RECIST 1.1) was 73.2%, and the secondary R0 surgery was 33%. With a median follow-up of 38.3 months, median OS was 37.4 months (95% CI, 25.7–45.8), and median PFS 10.8 months (95% CI, 8.2–12.3). Conclusions Front-line DEBIRI + mFOLFOX6 should not be recommended as the hypothesised 9-month PFS was not met. However, high response rate, deep responses, and prolonged OS encourage further evaluation in strategies integrating biologic agent, in particular in patients with secondary surgery as the main goal. Clinical trial registration NCT01839877.

American Radium Society Appropriate Use Criteria for the use of liver‐directed therapies for nonsurgical management of liver metastases: Systematic review and guidelines

“…Another study compared DEBIRI combined with FOLFOX versus FOLFOX alone in patients with unresectable CRC LM who were naïve to systemic chemotherapy. 97 An improvement in response rates was observed in the DEBIRI-FOLFOX group compared with the FOLFOX group, without observed increase in systemic toxicity. PFS was longer in the DEBIRI-FOLFOX group (15.2 months vs. 7.6 months), and more patients in the combination group became eligible for hepatic resection.…”

Safety, Feasibility and Technical Considerations from a Prospective, Observational Study—CIREL: Irinotecan-TACE for CRLM in 152 Patients

“…Historically, irinotecan-TACE was associated with salvage therapy for patients who had failed first, second, and third-line systemic chemotherapy. However, due to its favorable toxicity profile and high local efficacy, irinotecan-TACE can be an attractive loco-regional treatment for earlier stages of the continuum care for CRLM cancer, such as in combination with systemic therapy or to obtain a sustained disease control, allowing halt of treatment (e.g., “chemo-holidays”) and/or to alleviate the toxicity-burden of maintenance systemic treatment [ 29 , 30 ]. The interim analysis of the first 50 patients enrolled in CIREL has already reported the use of LP-irinotecan TACE beyond the former indications limited to “salvage” therapy settings, such as in combination with ablation, with curative intent, and even as a first-line treatment [ 31 ].…”

Review of Intra-Arterial Therapies for Colorectal Cancer Liver Metastasis

“…No significant difference in chemotherapy-associated adverse events were reported between the study arms. A more recent phase II study [ 71 ] evaluated 57 chemo-naïve patients with liver-dominant CRLM who received both DEBIRI and mFOLFOX6. The majority of patients received 4 DEBIRI sessions, in an alternating fashion between the right and left lobe, although 37% patients had bilobar treatment in 2 sessions which subsequently resulted in more serious toxicities encountered in this subgroup.…”