Introduction and objectives
In colorectal cancer liver metastases, Irinotecan-TACE has the potential to be used as either salvage therapy to achieve tumor control or as post-inductive/consolidation therapy, combined with systemic therapy or thermal ablation.
CIREL provides a pan-European perspective on the use of Irinotecan-TACE in routine clinical practice, reporting data on both treatment characteristics and clinical outcomes.
Study design and methodology
- Multi-center, prospective cohort study, enrolling patients from 20 centers in 11 European countries, from February 2018 to August 2020
- Adult patients with histologically confirmed colorectal cancer liver metastases, treated at least once with Irinotecan-TACE, using LifePearl™ microspheres
- Primary endpoint: Observed usage of Irinotecan-TACE, categorized as salvage therapy or postinductive/consolidation therapy
- Secondary outcomes:
- Tumor response assessed via RECIST v1.1 at baseline, follow-up 1 (0.5-2.5 months) and follow-up 2 (2.7-6.9 months)
- Overall survival (OS)
- Health-related quality of life (HRQoL), assessed through EORTC QLQ-C30 at baseline and 0.5-3.6 months follow-up
- Predictors for OS and (hepatic) progression-free survival (hPFS/PFS), estimated via multivariable Cox proportional hazards regression analyses
Results
Baseline characteristics
Efficacy
91 patients for whom independent image review was available at follow-up 1 or follow-up 2, the ORR was 9.9% (95% CI 6.2% to11.5%).
| Whole cohort
| Salvage therapy
| Post-Inductive/Consolidation Therapy
|
OS (months)
| 14.5, 95%CI [11.6-17.0]
| 9.9, 95%CI [7.4-12.8]
| 19.1, 95%CI [16.2-24.2]
|
PFS (months)
| 4.6, 95%CI [3.9-5.5]
| 3.8, 95%CI [2.9-4.7]
| 6.0, 95%CI [4.5-8.7]
|
hPFS (months)
| 6.2, 95%CI [5.0-7.1]
| 4.4, 95%CI [3.6-6.2]
| 8.7, 95%CI [6.9-10.6]
|
* salvage therapy is defined as patients progressing after at least one line of systemic therapy, and inductive/consolidation therapy as before/after systemic therapy or before/after other local ablative measures, mostly microwave ablation. These groups deviate from a previously published methodology (Pereira et al., 2020, Dig Liver Dis), as the initially intended granularity of indications to be captured could not be transformed into daily practice.
Predictors of survival
A multivariable Cox proportional hazards regression analysis identified some predictors of OS:
• ECOG performance status, 2 prior lines of systemic therapy and lesion size of > 50 mm as negative predictors for OS
• Incomplete treatment plans as a negative predictor for OS and hPFS, but not for PFS
• >50% liver involvement, and the presence of progressive extrahepatic metastases, unlike the presence of extrahepatic metastases in general, as negative predictors for OS and (h)PFS
Quality of Life
• Overall HRQoL was stable in 52% and improved in 14% of patients, deteriorated in 34% of the patients
• Certain symptoms, including pain, nausea and vomiting, fatigue, and appetite loss, showed significant deterioration
• However, other symptoms such as constipation, diarrhea, dyspnea, insomnia, and financial difficulties did not exhibit significant deterioration
Discussion and conclusion
Irinotecan-TACE is not only used as salvage therapy, but also frequently as post-inductive/consolidation therapy in European clinical practice. Effectiveness data indicate a relatively long OS in the salvage setting, and promising results in the post-inductive/consolidation setting, along with a stable overall HRQoL.
Study limitations include a high number of missing data points, the lack of control group, and the potential for unaccounted confounding factors.
Key Takeaways
- Irinotecan-TACE shows promising results on OS and tumor response in colorectal cancer liver metastases, both in the salvage setting and in combination with systemic therapy and ablation
- HRQoL is largely maintained during follow-up, in line with the minimally invasive nature of the procedure
- Irinotecan-TACE could be integrated further into systemic treatment pathways
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