Parameters associated with outcomes in pretreated MSI/dMMR metastatic colorectal cancer (mCRC) treated with immune checkpoint inhibitors (ICI): Subgroup analysis of a prospective cohort.

Abstract

3580 Background: Immune checkpoint inhibitors (ICI) have demonstrated efficacy in patients (pts) with MSI/dMMR mCRC. We aimed to evaluate clinical, pathological and molecular factors associated with progression-free survival (PFS) and overall survival (OS) in ICI-treated pretreated mCRC patients (pts). Methods: Pts are drawn from a prospective cohort of all patients treated with ICI for MSI/dMMR mCRC at Saint-Antoine Hospital, Paris, France. All MSI/dMMR mCRC pts with disease progression after ≥ 1 prior systemic treatment (fluoropyrimidine and oxaliplatin or irinotecan ± targeted therapy) were included. MSI/dMMR status was centrally reviewed. Lynch syndrome or sporadic status was determined according to MMR gene germline mutational testing, MLH1 methylation status and BRAFV600E mutation. PFS and objective response rate (ORR) were assessed using iRECIST criteria. The impact of Lynch syndrome on PFS was analyzed apart from the multivariate analysis due to the interaction with the BRAFV600E mutation status. Results: Of 130 included pts, 66 received anti-PD1 alone, 1 anti-PDL1 alone and 63 anti-PD1 plus anti-CTLA4. 71% have had at least 2 prior lines of treatment. 33 patients (25%) have BRAFV600Emutation (mt) and 49 (38%) RASmt. The ORR for the whole population was 62.8 % IC95% [53.8; 71.1]. Median follow-up was 21.0 months, median PFS and OS were not reached. Results of PFS unadjusted and adjusted analysis are displayed in the table. BRAFV600E and RAS mutation were not associated with PFS and OS in multivariate analyses. After adjustment for the treatment type, Hazard Ratio (HR) for PFS between patients with proven Lynch syndrome (N=44) and patients with proven sporadic tumors (n= 44) was 0.57 (95%IC 0.26 -1.26). Conclusions: In this cohort, main known clinical, pathological and molecular factors do not influence the efficacy of ICI in pre-treated MSI/dMMR mCRC.[Table: see text]