Patients and Disease Characteristics
This interim report includes the prospectively captured real-life use of LP-irinotecan TACE as a treatment for CRLM in the first 50 patients enrolled. Median age was 66 years; 29 patients (58%) were male. Patients and tumour characteristics are summarised in Table 1.
Liver metastases were synchronous in 68% and metachronous in 32% of patients. In total, 52% of those were located in the whole liver, 34%/14% limited to the right/left lobe, respectively. In total, 34% had a proven RAS mutation, 48% RAS wild-type status (18% unknown), 10% a proven BRAF mutation, 36% wild-type status, 54% unknown.
Before receiving LP-irinotecan TACE, 82% (41 patients) had received prior systemic chemotherapy for metastatic disease. In total, 18% (9 patients) were pretreated with one line, 12% (6 patients) with two lines and 52% (26 patients) with 3 or more treatment lines. Of the overall population 36% received anti-angiogenic and 20% anti-EGFR targeted therapy. In 20%, liver metastases had been resected with 4% of the total population having received adjuvant fluoropyrimidines and oxaliplatin and 4% having received adjuvant irinotecan. Prior ablation and intra-arterial liver-directed treatment were seen in 10% and 12% of patients.
LP-Irinotecan TACE Treatment and Treatment Intention
Information on 129 LP-irinotecan TACE treatment sessions in our 50 patients is shown in Table 2.
In total, 50% of patients received treatments in only one liver lobe (unilobar), with a median number of 2 sessions per patient (78% right lobe, 22% left lobe). The median number of treatments where both lobes were targeted alternatingly (bilobar) per patient was 2.6 sessions. The median intended dose per session was 100 mg (80% of patients) using a bead size of 100 µm (86%). Treatments were considered technically successful in 100% of cases, showing either a complete stasis in 36% or a complete delivery of dose in 64%.
For most patients, intention of LP-irinotecan TACE was salvage therapy (42%; 21 patients), meaning the patients had progressive disease and received three or more lines of chemotherapy before. LP- irinotecan TACE treatment was intended in 20% (10 patients) as an intensification treatment with concomitant systemic therapy for patients with progressive disease but maximum two previous lines of chemotherapy and 14% (7 patients) as a consolidation treatment with or without systemic chemotherapy for patients with stable disease. Only 16% and 8% (8 and 4 patients, respectively) of treatments were classified as first line for chemo-naive patients or patients that have not received prior systemic chemotherapy for the liver metastases and combination treatment with ablation with curative intent, respectively. Treatment intentions were distributed evenly across high-enrolling sites (supplementary Table 3).
When analysing peri-procedural medications, we observed different treatment strategies in different sites as seen in Fig. 1. While opioids were used in almost all sessions, some patients received additional medication such as local anaesthesia, additional non-opioid pain- or anti-inflammatory medication, anti-histamine, antibiotics and antiemetics.
Safety and Toxicity
Abnormal laboratory values of grade 3 or 4 were observed 7 times in 4 patients before the first treatment and 11 times in 5 patients before subsequent LP-irinotecan TACE treatments (Table 3). Haematological, renal and hepatic toxicity was only observed by single abnormal laboratory values of grade 3 and 4 in individual patients with no increase compared to abnormal laboratory values of grade 3 and 4 before the first treatment session.
Adverse events (AE) are summarised in Table 4. In total, 33 peri-interventional AEs were reported, with 26% of patients having experienced at least one AE. Most notably, patients were experiencing grade 1 and grade 2 post-embolisation syndrome, which is defined as pain, fever or nausea/vomiting, with grade 1 pain being reported most frequently.
Within 30 days following the last treatment, 20% (10 patients) experienced at least one AE. Grade 3 and 4 AEs were reported for 10% (5 patients). One patient experienced a grade 4 AE (colonic obstruction and sepsis), as well as a grade 3 AE (hepatic failure and blood bilirubin increase). Another patient experienced a grade 3 AE (renal failure and hyperkalemia), and one patient a grade 3 AE (infection and CPR increase) and one last patient experienced a grade 3 AE(abscess). No adverse event resulting in mortality was reported in the 30 days after the last treatment.
Health-Related Quality of Life Analysis
Median HRQOL deteriorated over time, as both—median global health and median functional—scores decreased and the median symptom score increased (Fig. 2). Figure 2a, c, e shows the difference in median HRQOL for 34 patients for the first follow-up compared to the baseline scores of the same patients. Median global health, functional and symptom score before the first LP-irinotecan TACE treatment was 75.0, 91.1 and 8.3, respectively, and 66.7, 88.5 and 11.1, at the first follow-up. When looking at the patients individually, we see that for the majority of patients the global health, functional and symptom scores remained similar or improved (Fig. 2b, d, f).
In total, 62% of patients reported that the global health status stayed the same or improved (18%) and 38% of patients showed a decrease of global health. For the functional score, 74% of patients reported a stable or increased (3%) score and 26% of patients reported a worsening of the functional score. For the symptom score 82% reported stable or improved (3%) score and 18% reported worsening of the symptom score. When looking at patients with deterioration in global health, functionality and symptoms, we observed that 54%, 77% and 50%, respectively, were salvage therapy patients (see Fig. 2b, d, f, red bars).