PT - JOURNAL ARTICLE AU - FucĂ , Giovanni AU - Corti, Francesca AU - Ambrosini, Margherita AU - Intini, Rossana AU - Salati, Massimiliano AU - Fenocchio, Elisabetta AU - Manca, Paolo AU - Manai, Chiara AU - Daniel, Francesca AU - Raimondi, Alessandra AU - Morano, Federica AU - Corallo, Salvatore AU - Prisciandaro, Michele AU - Spallanzani, Andrea AU - QuarĂ , Virginia AU - Belli, Carmen AU - Vaiani, Marta AU - Curigliano, Giuseppe AU - Cremolini, Chiara AU - De Braud, Filippo AU - Di Bartolomeo, Maria AU - Zagonel, Vittorina AU - Lonardi, Sara AU - Pietrantonio, Filippo TI - Prognostic impact of early tumor shrinkage and depth of response in patients with microsatellite instability-high metastatic colorectal cancer receiving immune checkpoint inhibitors AID - 10.1136/jitc-2021-002501 DP - 2021 Apr 01 TA - Journal for ImmunoTherapy of Cancer PG - e002501 VI - 9 IP - 4 4099 - http://jitc.bmj.com/content/9/4/e002501.short 4100 - http://jitc.bmj.com/content/9/4/e002501.full SO - J Immunother Cancer2021 Apr 01; 9 AB - Background Immune checkpoint inhibitors (ICIs) are the new standard of care in microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC). Since tumor response dynamic parameters already shown a strong association with survival outcomes in patients with mCRC treated with first-line therapy, we investigated the association of early tumor shrinkage (ETS) and depth of response (DoR) in patients with MSI-H/dMMR mCRC treated with ICIs.Methods This is a retrospective, multicenter, cohort study in patients with dMMR and/or MSI-high mCRC treated with ICIs (anti-PD-1/PD-L1 with or without anti-CTLA-4 agents) with measurable disease and at least one post-baseline radiological disease reassessment. The Kaplan-Meier method and Cox proportional-hazards regression models were used for survival analyses. A maximally selected statistics method in a Cox regression model for progression-free survival (PFS) was used to determine the optimal cut-offs for ETS and DoR.Results We included a total of 169 patients: 116 (68.6%) were treated with anti-PD-1 monotherapy, whereas 53 (31.4%) with anti-PD-1 plus anti-CTLA-4 agents. Patients with primary progressive disease (N=37, 21.9%), experienced an extremely poor overall survival (OS) and were evaluated separately. In patients with clinical benefit, we observed a significant association between ETS and DoR with both OS and PFS, and we identified a relative reduction of at least 1% as the optimal cut-off for ETS and a relative reduction of at least 50% as the optimal cut-off for DoR.Conclusions ETS and DoR are important prognostic factors in patients with MSI-high mCRC treated with ICIs that might be useful to design treatment intensification/deintensification strategies. A prospective validation of both is warranted.Data are available on reasonable request. The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.