Results from CIREL—the largest, pan-European, prospective study of irinotecan-eluting transarterial chemoembolization (TACE) for colorectal liver metastases (CRLMs), show a comparably long median overall survival (OS) when used as salvage therapy and “promising” hepatic progression-free survival (HPFS) when used with systemic therapy or thermal ablation as a post-inductive or consolidation therapy.
The study, published in European Society for Medical Oncology (ESMO) Open by Dirk Arnold (Asklepios Tumor Centre Hamburg, Hamburg, Germany) et al, was led by Philippe L Pereira (SLK Kliniken Heilbronn, Germany) and Julien Taieb (Georges Pompidou European Hospital, Paris, France), who sought to evaluate when and for whom irinotecan-TACE should be preferred over other locoregional treatments, or may be added to other treatments.
CIREL was conducted across 11 European countries including 20 centres, and enrolled 152 patients in total between February 2018 and August 2020. Patients aged ≥18 years with histologically confirmed CRLMs were eligible for inclusion following a multidisciplinary team (MDT) decision to be treated with irinotecan-TACE. All patients underwent at least one treatment session with LifePearl (MicroVention) microspheres and attended follow-up sessions between 4–8 weeks and 12–16 weeks following the last treatment session. Subsequent follow-up was then conducted every eight weeks until loss to follow-up, death or until the end of data collection.
The primary endpoint of the study was to identify the number of indications that the device is used for, assessed by stage and previous treatment(s). To this end, irinotecan-TACE was categorised into two treatment intentions: salvage therapy, which was defined by the authors as intensification of treatment with concomitant systemic therapy, and salvage treatment in progressive patients pre-treated with systemic therapy, with or without concomitant systemic therapy, and, as post-inductive/consolidation therapy, defined as LifePearl irinotecan as a first-line, consolidation or closing treatment with or without systemic therapy, or as combination treatment with ablation with curative intent.
The study cohort had an average age of 66 years, 61.2% of patients were male and extrahepatic metastases were present in 56.6% of patients. Irinotecan-TACE was used in 57.2% of patients as salvage therapy for those who had progressive disease after at least one line of systemic therapy, whereas 42.8% of patients received irinotecan-TACE as a post inductive/consolidation therapy with irinotecan-TACE before/after systemic therapy or before/after thermal ablation. The prespecified treatment plan was completed in 89% and 72% of patients in each respective group.
Overall, the median OS was 14.5 months. In the irinotecan-TACE as salvage therapy group, median OS was 9.9 months (7.4–12.8 months) and the median PFS was 3.8 months (2.9–4.7 months). The median OS for the treatment as post-inductive or consolidation therapy when used in combination with systemic therapy or thermal ablation was 19.1 months (16.2–24.2 months), and the median PFS was six months (4.5–8.7 months).
The authors highlight that the median HPFS was 6.2% with six- and 12-month HPFS rates of 52% and 24%, respectively. In the irinotecan-TACE as post-inductive/consolidation therapy group, HPFS was reported as 8.7 months, which “since irinotecan-TACE is a locoregional treatment that acts directly in the liver, an HPFS of 8.7 of the post-inductive/consolidation therapy should be highlighted”, state the authors.
Following a multivariable analysis, Arnold et al identified negative prognostic factors to be Eastern Cooperative Oncology Group performance status ≥2, >50mm lesion size, progressive extrahepatic disease, ≥2 prior systemic therapy lines, and >50% liver involvement. For PFS, progressive disease outside the liver and liver involvement of 25%-50%, or >50%, were identified as negative prognostic factors. Health-related quality of life (HRQoL) score was generally stable or improved overall, Arnold and colleague state.
“In both cohorts of patients receiving either salvage or post-inductive/consolidation therapy, HRQoL considerations can contribute to a better understanding of patient-oriented treatment selection,” Arnold and colleagues write. “Ultimately, since irinotecan-TACE is a locoregional therapy that can be repeated for progressive or new lesions or followed up by other locoregional or systemic therapies, early response and disease control should not be neglected.”
Moreover, the authors emphasise the potential for irinotecan-TACE to be combined with other treatment strategies to “either intensify the liver-directed treatment or target extrahepatic disease”. However, randomised trials are needed to provide “robust evidence on how irinotecan-TACE can be integrated into a treatment pathway that minimises patient burden while preserving HRQoL”, Arnold et al conclude.
