5206 - Updated results of NORDIC 8, a randomised trial of cetuximab every 2 weeks with FOLFIRI or cetuximab with alternating FOLFIRI/FOLFOX in patients with RAS and BRAF wild type metastatic colorectal cancer.

Background

Cetuximab (cet) improves efficacy of first-line FOLFIRI in pts with RAS/RAFwt metastatic colorectal cancer (mCRC). Triplet chemotherapy improves efficacy further but with increased toxicity. Alternating FOLFIRI/FOLFOX is a different way to administer all 3 cytotoxic drugs. We report the updated results from Nordic 8, a multi-centre, randomised trial comparing cet with FOLFIRI (arm A) or with FOLFIRI alternating with FOLFOX (arm B).

Methods

In this investigator initiated randomised trial, 173 chemo-naïve mCRC patients received cet with FOLFIRI or cet with FOLFIRI (2 cycles) alternating with FOLFOX until PD. Main inclusion criteria were PS 0 or 1, RASwt and ESMO group 1-3 (prior to April 2014 only ESMO group 1 when 36 patients had been included)). The primary endpoint was RR (increase from 60% to 75%) and secondary endpoints were PFS, OS and safety. All endpoints were evaluated by the local investigator.

Results

From May 2012 to May 2018, 173 patients were randomized. Median age was 64 years (25% were at least 70 years), female 34%, PS 0 61%, ESMO group 1/2/3 64%/23%/13%. Baseline characteristics were well-balanced between the two groups. Median duration of therapy was 6.2 months in both arms and patients received a median of 11 and 12 cycles, respectively, without any difference in dose-intensity. In arm A and B overall RR was 69% and 78% (p = 0.17), median PFS was 11.9 (arm A) and 11.8 months (arm B) (HR 1.10; p = 0.60), and median OS was 40.7 and 39.2 months (HR 1.05; p = 0.82), respectively. Most important grade ≥ 3 adverse events were neutropenia (15% vs 17%), rash (9% vs 15%), diarrhoea (7% vs 11%), fatigue (7% vs 7%), and febrile neutropenia (3% vs 1%); 20% in arm B experienced neuropathy grade 2 (no grade 3). Final and updated PFS and OS with sub-group analysis will be presented.

Conclusions

Cet every two weeks in combination with FOLFIRI or alternating FOLFIRI/FOLFOX is well tolerated with high RR and long OS. We recommend FOLFIRI + cet every 2 weeks in patients with RAS and BRAFwt mCRC.

Clinical trial identification

2011-004188-65.

Editorial acknowledgement

Legal entity responsible for the study

Nordic Biomodulation Group.

Funding

Merck.

Disclosure

C. Kersten: Research grant / Funding (institution), Licensing / Royalties, Relationship is unrelated to this study: Merck KGaA. All other authors have declared no conflicts of interest.