56P - Systemic inflammation in liver vs non-liver metastatic microsatellite stable (MSS) colorectal cancer (CRC): An analysis of 2186 patients (pts) from the observational study BMI-QoL and the phase II and III trials MACBETH, MOMA, ATEZOTRIBE, TRIBE, TRIBE2, T

Background

Liver metastases (mets) from MSS CRC have been associated with worse clinical outcome with immunotherapy. We investigated whether this might be due to a significant difference in unfavourable systemic inflammatory indexes.

Methods

Differences in 8 inflammatory markers were assessed in liver vs non-liver MSS mCRC pts treated with 1° line regimens. 128 pts from the BMI-QoL observational study (NCT03873064) were initially analysed. Findings from BMI-QoL were then validated in 2058 pts from phase II and III trials that were split in a discovery (70%) and a validation (30%) subset. The discovery subset was used to identify optimal variable cutoffs associated with liver mets which were then confirmed in the validation subset. The identified cutoffs were assessed for prediction of progression free and overall survival (PFS and OS).

Results

In the BMI-QoL cohort neutrophils(NEU), platelets (PLT) and Systemic Inflammatory Index (SII) were significantly different between liver and non-liver (p 0.003, 0.007 and 0.005, respectively). In the phase II/III trial cohort NEU, PLT, SII but also lymphocytes were found to be significantly different, with NEU being the most significant marker: median(m) NEU 5.0 vs 4.4*10⁶/μL in liver vs non-liver, respectively, p < 0.0001. In the discovery subset the optimal NEU cutoff was >5.0*10⁶/μL (NEU^high) and this was confirmed in the validation subset. Prevalence of NEU^high was 49% vs 37% in liver vs non-liver, respectively, p<0.0001. NEU^high was associated with shorter mPFS in liver but not in non-liver: NEU^high vs NEU^low 10.5 vs 12.1 months, HR 1.29, p<0.0001 and 11.7 vs 13.1, HR 1.09, p 0.489, respectively. Also in terms of mOS, NEU^high had the worst survival in liver pts: NEU^high vs NEU^low 23.7 vs 31.9 months in liver, HR 1.55, p<0.0001 and 28.3 vs 43.9 months in non-liver, HR 1.60, p 0.002, respectively.

Conclusions

Liver mets from MSS CRC were associated with high NEU which may partly account for the reduced efficacy of immunotherapy observed in this subgroup. Given the particularly unfavourable outcome, there is an urgent need for effective treatments for these patients.

Legal entity responsible for the study

GONO.

Funding

Has not received any funding.

Disclosure

V. Formica: Financial Interests, Personal, Invited Speaker: Merck, Servier, Amgen, Pierre Fabre. C. Cremolini: Financial Interests, Personal, Advisory Board: Roche, MSD, Pierre Fabre, Nordic Pharma, Takeda; Financial Interests, Personal, Invited Speaker: Bayer, Servier, Merck Serono; Financial Interests, Personal, Expert Testimony: Amgen; Financial Interests, Institutional, Invited Speaker: Roche, Bayer, Servier, Merck, Seagen, Hutchinson. A. Zaniboni: Financial Interests, Personal, Invited Speaker: Servier, Bristol, MSD, Merck Serono, Amgen, Pierre Fabre. F. Bergamo: Financial Interests, Personal, Invited Speaker: Lilly, BMS, MSD, Eisai, Bayer, Amgen; Financial Interests, Personal, Advisory Board: Servier, AAA; Other, congress: Bayer, Ipsen, AAA. All other authors have declared no conflicts of interest.