RT Journal Article
SR Electronic
T1 Prognostic impact of early tumor shrinkage and depth of response in patients with microsatellite instability-high metastatic colorectal cancer receiving immune checkpoint inhibitors
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e002501
DO 10.1136/jitc-2021-002501
VO 9
IS 4
A1 Fucà, Giovanni
A1 Corti, Francesca
A1 Ambrosini, Margherita
A1 Intini, Rossana
A1 Salati, Massimiliano
A1 Fenocchio, Elisabetta
A1 Manca, Paolo
A1 Manai, Chiara
A1 Daniel, Francesca
A1 Raimondi, Alessandra
A1 Morano, Federica
A1 Corallo, Salvatore
A1 Prisciandaro, Michele
A1 Spallanzani, Andrea
A1 Quarà, Virginia
A1 Belli, Carmen
A1 Vaiani, Marta
A1 Curigliano, Giuseppe
A1 Cremolini, Chiara
A1 De Braud, Filippo
A1 Di Bartolomeo, Maria
A1 Zagonel, Vittorina
A1 Lonardi, Sara
A1 Pietrantonio, Filippo
YR 2021
UL http://jitc.bmj.com/content/9/4/e002501.abstract
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.