The hepatic artery accounts for the primary blood supply of liver metastases from CRC.
First-line therapy with up to 12 series of HAI with oxaliplatin 100 mg/m2 day 1 and capecitabine 3500 mg/m2 day 1-7 every second week. When the hepatic arterial anatomy did not permit a permanent catheter pts had intravenous oxaliplatin 130 mg/m2 day 1 every third week combined with capecitabine 2000 mg/m2 day 1-14 (CAPOX). RAS mutations were retrospectively determined by next generation sequencing of KRAS Exon (E) 2, codon (C) 12 and 13, E3C59 and 61, E4C117 and 146 and NRAS E2C12 and 13, E3C59 and 61, E4C117 and 146. Pts had a baseline PET/CT scan and was evaluated by liver surgeons for resectability.
Included were 93 pts, 66 had HAI and 27 CAPOX. The groups were comparable with an equal distribution of RAS wildtype (RAS-W) and mutants (RAS-M) tumours. Follow-up was 95-154 mths. Overall response rate (ORR) with complete (CR) and partial remission (PR) was 89% vs 59% in the HAI vs. CAPOX group (P = 0.0008). Progression-free survival (PFS) was independent of RAS status and treatment. Median overall survival (OS) was 6 mths. longer in the HAI vs CAPOX group (HR 1.62, 95% Confidence Interval (CI) 1.0-2.6, P = 0.05). OS was independent of RAS status in the CAPOX group and equal to OS in the HAI RAS-M group. Pts with RAS-W tumours treated with HAI survived double that of all the other groups (HAI-RAS-W vs HAI-RAS-M: HR 1.88, 95%CI 1.1-3.2, P = 0.023, HAI-RAS-W vs. CAPOX-RAS-W: HR 1.60 95%CI 1.12-2.27, P = 0.009). Toxicity of HAI was comparable to CAPOX with abdominal pain, neuropathy, and hand foot syndrome as the most common adverse events.Table: 518P
|PR||51 (77%)||25||26||16 (59%)||10||6|
|mOS 1||36 (28-44)||64 (45-81)||29 (24-35)||30 (24-35)||30 (20-41)||22 (16-29)|
|mPFS 1||12 (10-15)||14 (11-17)||11 (8-15)||11 (9-13)||12 (7-17)||10 (8-13)|
Mths with 95%CI in brackets. NA=not applicable, SD =stable disease and PD=progressive disease.
ORR and OS was significantly higher when pts with LLmCRC was treated with Capecitabine and HAI with oxaliplatin compared to CAPOX. Survival benefit is limited to pts with RAS-W tumours treated with HAI.
Clinical trial identification
Legal entity responsible for the study
Benny Villars Vittrup.
The Danish Cancer Society.
All authors have declared no conflicts of interest.