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 Giovanni Fucà
A1 Francesca Corti
A1 Margherita Ambrosini
A1 Rossana Intini
A1 Massimiliano Salati
A1 Elisabetta Fenocchio
A1 Paolo Manca
A1 Chiara Manai
A1 Francesca Daniel
A1 Alessandra Raimondi
A1 Federica Morano
A1 Salvatore Corallo
A1 Michele Prisciandaro
A1 Andrea Spallanzani
A1 Virginia Quarà
A1 Carmen Belli
A1 Marta Vaiani
A1 Giuseppe Curigliano
A1 Chiara Cremolini
A1 Filippo De Braud
A1 Maria Di Bartolomeo
A1 Vittorina Zagonel
A1 Sara Lonardi
A1 Filippo Pietrantonio
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.