LBA27 - 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

Background

CAIRO5 aimed to find the optimal systemic induction regimen to convert initially unresectable CRLM to local treatment.Previously, we showed that for patients with right-sided and/or RAS/BRAFV600E mutated tumours PFS was significantly longer and complete local treatment (R0/R1 resection and/or ablation) higher with FOLFOXIRI vs FOLFOX/FOLFIRI, both plus bevacizumab. For patients with left-sided and RAS/BRAFV600E wild-type tumours these parameters were not different between adding panitumumab vs bevacizumab to FOLFOX/FOLFIRI.

Methods

Patients with right-sided and/or RAS/BRAFV600E mutated tumours randomly received FOLFOX/FOLFIRI-bevacizumab (arm A) or FOLFOXIRI-bevacizumab (arm B), and with left-sided and RAS/BRAFV600E wild-type tumours FOLFOX/FOLFIRI-bevacizumab (arm C) or FOLFOX/FOLFIRI-panitumumab (arm D). Resectability was assessed by an expert panel of surgeons and radiologists at baseline and 2-monthly thereafter. Patients were stratified by potentially resectable vs permanently unresectable, serum LDH, irinotecan vs oxaliplatin, and BRAFV600E mutation status (arm A/B). Overall survival (OS, secondary endpoint) was compared with a stratified log-rank test and hazard ratios were calculated with a Cox proportional hazards model.

Results

Between November 2014 and January 2022, 530 patients were randomised in 47 centres, 148/146/118/118 in arms A/B/C/D. 9 ineligible patients were excluded. Median follow up was 57 months. Median OS in arm A vs B was 23.6 vs 24.1 months (HR 0.92, 95% CI 0.70 – 1.20, p=0.52) with 229 events. Median OS in arm C vs D was 40.4 vs 38.3 months (HR 1.02, 95% CI 0.72 – 1.46, p=0.89) with 134 events. Recurrence within 6 months after complete local treatment occurred in 26 (49%) vs 29 (39%) patients in arm A vs B (p=0.28), and 28 (42%) vs 26 (39%) patients in arm C vs D (p=0.73).

Conclusions

In patients with initially unresectable CRLM, OS was not different between FOLFOXIRI-bevacizumab and FOLFOX/FOLFIRI-bevacizumab for right-sided and/or RAS/BRAFV600E mutated tumours, nor between adding panitumumab vs bevacizumab to FOLFOX/FOLFIRI for left-sided and RAS/BRAFV600E wild-type tumours.

Clinical trial identification

NCT02162563, EudraCT 2013-005435-24.

Editorial acknowledgement

Legal entity responsible for the study

Dutch Colorectal Cancer Group.

Funding

This study was supported by unrestricted grants from Roche and Amgen. The funders had no role in the design, conduct and submission of the study, nor the decision to submit the abstract for publication.

Disclosure

C.J.A. Punt: Financial Interests, Institutional, Advisory Board: Nordic Group BV. J.W. de Groot: Financial Interests, Advisory Role: BMS. All other authors have declared no conflicts of interest.