Association of high microsatellite instability (MSI-H) with a high immunoscore (IS) compared to PD-L1 expression and increased survival in patients (pts) with metastatic colorectal cancer (mCRC) treated with oxaliplatin (Ox) and fluoropyrimidine (FP): A pooled analysis of the AIO KRK 0207 and RO91 trials.

3595 Background: MSI-H is an established prognostic marker in early colon cancer. Moreover, MSI-H, tumor immune cell infiltration and PD-L1 expression are also discussed as potential predictive biomarkers for immunotherapy. However, little is known about the prognostic value of these biomarkers and their association among each other in mCRC. Methods: We analyzed samples from pts. with mCRC uniformly treated with a FP and Ox within two randomized AIO trials (KRK 0207 and RO91). MS status was assessed by immunohistochemistry (IHC) of mismatch repair proteins and subsequent fragment length analysis in case of protein loss or incoherent results. PD-L1 expression was determined by IHC (1% expression threshold). Tumor lymphocytic infiltration (CD8 and CD45RO) was scored according to the immunoscore (IS) concept by Galon et al (J Transl Med 2016). Results: 41/550 cases (7.5%) displayed MSI-H. The mean IS of the total population was 0.57 (SD 0.97), the IS of MSI-H pts. was significantly higher (mean of 2.4; SD 1.4; p≤0.0001). 17 cases were PD-L1 positive (pos.) (3 %), only four of these were MSI-H. MSI-H status was significantly correlated with a higher IS, but not with PD-L1 expression (table 1). There was no difference in median overall survival (mOS) between MSI-H and MS stable (MSS) pts. (mOS MSI-H/MSS: 17.6/22.5 months (mos.), log rank: p=0.85), PD-L1 negative (neg.) and pos. pts. (mOS PD-L1 neg./pos.: 22.1/28.9 mos., log rank: p=0.49) and IS high or low pts. (mOS IS high/low: 21.1/22.1mo., log rank: p=0.25). Conclusions: In contrast to early stage colon cancer, none of these parameters was prognostic in mCRC patients. Panel-sequencing with a total of 35 genes including RAS, BRAF and POL-E on cases with PD-L1 expression, high IS or MSI-H status to further characterize these cases will be reported. Clinical trial information: AIO-R091, AIO-KRK-0207: EudraCT-Nr: 2008-007974-39. [Table: see text]