632P - Predictive value of C-reactive protein (CRP) in microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) patients given first-line alternating short-course oxaliplatin-based chemotherapy (FLOX) and nivolumab

Background

Tumour-associated systemic inflammation impedes immune checkpoint blockade (ICB) efficacy. We explored whether the initial two FLOX cycles of alternating short-course FLOX and nivolumab may affect circulating CRP and outcome (progression-free survival; PFS) in first-line treatment of MSS-mCRC.

Methods

In the METIMMOX randomised trial, patients were assigned to FLOX (oxaliplatin 85 mg/m² day 1, bolus 5-fluorouracil 500 mg/m² and folinic acid 100 mg day 1-2) Q2W (control arm) or alternating two cycles each of FLOX and nivolumab (240 mg) Q2W (experimental arm) with PFS as the primary endpoint. CRP was measured at baseline and every treatment visit. In this post hoc analysis, patients were categorised based on CRP ≥5.0 mg/L and <5.0 mg/L after the initial two FLOX cycles, immediately before the third FLOX (control arm) or first nivolumab (experimental arm) cycle was started.

Results

Patients were randomly assigned 2018/05-2021/10. At censoring 2023/01, median PFS was 9.3 months in both study arms. For the entire cohort, CRP was median 13.0 mg/L (range 0.70-112) at baseline (n=76) and 6.0 mg/L (range 0.50-60.0) after two FLOX cycles (n=73); p=0.014 (Mann-Whitney U-test). For experimental-arm patients, CRP <5.0 mg/L immediately before commencing nivolumab (n=17) was associated with significantly improved median PFS 15.7 months (range 2.6-41.6) compared to patients with CRP ≥5.0 mg/L (n=19) with median PFS 4.4 months (range 1.9-17.1); p=0.0004 (log-rank). No such difference was seen in the control arm; p=0.82 (log-rank). Experimental-arm patients with CRP <5.0 mg/L after the first two FLOX cycles had longer PFS compared to the corresponding control group; p=0.0082 (log-rank).

Conclusions

In MSS-mCRC patients receiving first-line therapy, CRP <5.0 mg/L after initial two FLOX cycles identified patients responding to sequential nivolumab with improved PFS compared to patients continuing FLOX. As a rapid, cost-effective analysis, and if early oxaliplatin-based chemotherapy counteracts tumour-associated systemic inflammation, CRP may predict ICB efficacy in MSS-mCRC.

Clinical trial identification

NCT03388190.

Editorial acknowledgement

Legal entity responsible for the study

A. H. Ree.

Funding

This work is supported by the Norwegian Cancer Society, including its Umbrella Foundation for Cancer Research (Grants 182496 and 215613), the South-Eastern Norway Regional Health Authority (Grant 18054) and Bristol Myers Squibb (by providing nivolumab free of charge and an associated research grant).

Disclosure

H.M. Hamre: Financial Interests, Personal, Invited Speaker, Personal Honorarium: Bayer; Financial Interests, Personal, Invited Speaker, Personal honorarium: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai, Incyte. C. Kersten: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche. H. Sorbye: Financial Interests, Personal, Invited Speaker, Personal honorarium: Ipsen, Pierre Fabre, SAM Nordic; Financial Interests, Personal, Advisory Board: Bayer, Hutchison MediPharma, ITM, AAA Pharma. A.H. Ree: Financial Interests, Institutional, Funding: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, Personal Honorarium: MSD. All other authors have declared no conflicts of interest.