Abstract 112P
Background
Preliminary evidence suggests that liver metastases (LM) have an immune-suppressive tumor microenvironment and are associated with poor efficacy of immune checkpoint inhibitor (ICI) in different solid malignancies. However, limited data are available from randomized clinical trials investigating ICI-based treatments in mCRC. We performed a comprehensive evaluation of LM among mCRC patients enrolled in the phase II randomized AtezoTRIBE trial, that showed a modest benefit from the addition of atezolizumab (atezo) to 1-line FOLFOXIRI/bevacizumab (bev) and identified Immunoscore IC as a predictor of ICI efficacy in the proficient mismatch repair (pMMR) population.
Methods
We investigated the association of LM disease with tumor immune-related biomarkers – including MMR, TMB, Immunoscore IC, Immunoscore, Tumor-Infiltrating lymphocytes (TILs) assessed by optical microscope, PD-L1 expression by Tumor Proportion Score (TPS), and the immune 27-gene signature DetermaIO – and treatment outcome, in the cohort of patients with pMMR tumor enrolled in the AtezoTRIBE study.
Results
151 (75%) out of 202 enrolled patients with pMMR tumor had LM. No differences in terms of immune-related features were observed between tumors with and without LM, with the exception of a lower prevalence of high TILs-tumors in the presence of LM (33% vs 52%, p =0.03). Immunoscore IC was more frequently high in the absence of LM but without reaching statistical significance (45% vs 28%, p =0.09). LM disease had a negative prognostic impact both in the FOLFOXIRI/bev (HR for PFS 1.81 [95% CI: 1.02-3.21]; HR for OS 2.00 [95% CI: 1.01-3.99]) and in the FOLFOXIRI/bev/atezo arm (HR for PFS 1.75 [95% CI: 1.18-2.61]; HR for OS 1.69 [95% CI: 1.04-2.75]), confirmed in the multivariable models. No interaction effect between the presence or not of LM and treatment arm was evident in terms of both PFS (p=0.99) and OS (p=0.80).
Conclusions
In our cohort of pMMR mCRC patients, the immune microenvironment of tumors with LM spread does not differ from that of tumors with no liver involvement. The presence or not of LM does not affect the efficacy of adding atezo to first-line FOLFOXIRI/bev, differently than Immunoscore IC.
Legal entity responsible for the study
GONO foundation.
Funding
Has not received any funding.
Disclosure
D. Rossini: Financial Interests, Personal, Other, Honoraria: Merck Sharp & Dohme (MSD). S. Lonardi: Financial Interests, Institutional, Advisory Board: Amgen, Merck Serono, Lilly, AstraZeneca, Incyte, Daiichi Sankyo, BMS, Servier, and MSD; Financial Interests, Institutional, Funding: Amgen, Merck Serono, Bayer, Roche, Lilly, AstraZeneca, and BMS; Financial Interests, Personal, Invited Speaker: Roche, Lilly, BMS, Servier, Merck Serono, Pierre Fabre, GSK, and Amgen. J. Galon: Financial Interests, Institutional, Other, Co-Founder: HalioDx. C. Cremolini: Financial Interests, Personal, Other, Personal fees: Roche, Amgen, Bayer, Servier, Merck, MSD, Pierre Fabre, Nordic Pharma, and Organon; Financial Interests, Institutional, Funding: Merck Serono, Servier, Bayer, and Amgen; Financial Interests, Institutional, Advisory Board: Bayer, Amgen, Servier, Pierre Fabre. All other authors have declared no conflicts of interest.