Overall survival in patients with initially unresectable colorectal liver metastases does not depend on choice of induction regimen 

CAIRO5, the first randomised study to prospectively evaluate 4 systemic induction regiments in patients with initially unresectable colorectal cancer liver metastases (CRLM), did not find differences in overall survival (OS).

Patients with initially unresectable CRLM might qualify for local treatment with curative intent after reducing the tumour size by induction systemic treatment. The current phase 3 CAIRO5 trial (NCT02162563) aimed to find the optimal systemic induction regimen to convert initially unresectable CRLM to local treatment in 121 participants. Previously, it was reported that the progression-free survival was significantly longer and the complete local treatment (R0/R1 resection and/or ablation) higher with FOLFOXIRI (arm A) versus FOLFOX/FOLFIRI (arm B), both plus bevacizumab for participants with right-sided and/or RAS/BRAF^V600E-mutated tumours [1]. For patients with left-sided and RAS/BRAF ^V600 wildtype tumours, these parameters were not different between adding bevacizumab (arm C) versus panitumumab (arm D) to FOLFOX/FOLFIRI. Prof. Cornelis J. Punt (University Medical Center Utrecht, the Netherlands) presented the OS results from the CAIRO5 trial [2].

The median follow-up was 58 months and the median OS in arm A versus B was 23.6 months versus 24.1 months (HR 0.92; 95% CI 0.70–1.20; P=0.52). In both arms A and B, OS in participants who had local treatment was significantly longer than OS in participants without local treatment (HR 0.27 vs 0.30 in arm A vs arm B, respectively). The median OS in arm C versus D was 40.4 months versus 38.3 months (HR 1.02; 95% CI 0.72–1.46; P=0.89). As for arms A and B, OS in participants who had local treatment in arms C and D was significantly better compared with participants without local treatment (HR 0.22 and HR 0.19). Recurrence within 6 months after complete local treatment occurred in 49% versus 39% of participants in arm A versus B (P=0.28), and 42% versus 39% of participants in arm C versus D (P=0.73).

“In this first randomised study to prospectively evaluate 4 systemic induction regimens in participants with initially unresectable CRLM, no benefit in median OS was observed

between FOLFOXIRI-bevacizumab and FOLFOX/FOLFIRI-bevacizumab for right-sided and/or RAS/BRAF^V600E-mutated tumours, nor between adding panitumumab versus bevacizumab to FOLFOX/FOLFIRI for left-sided and RAS/BRAF ^V600 wildtype tumours,” concluded Prof. Punt.

1. 
   
   1. Bond MJG, et al. Lancet Oncol. 2023;24(7):757–771.
   2. Punt CJ, et al. First-line systemic treatment in patients with initially unresectable colorectal cancer liver metastases (CRLM): overall survival of the phase III CAIRO5 study of the Dutch Colorectal Cancer Group. Abstract LBA27, ESMO 2023, 20-24 October, Madrid, Spain.

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Posted on 18 December, 202318 December, 2023