Prognostic impact of early tumor shrinkage and depth of response in patients with microsatellite instability-high metastatic colorectal cancer receiving immune checkpoint inhibitors

• Published in: Journal for immunotherapy of cancer Vol. 9; no. 4; p. e002501
• Main Authors: Fucà, Giovanni, Corti, Francesca, Ambrosini, Margherita, Intini, Rossana, Salati, Massimiliano, Fenocchio, Elisabetta, Manca, Paolo, Manai, Chiara, Daniel, Francesca, Raimondi, Alessandra, Morano, Federica, Corallo, Salvatore, Prisciandaro, Michele, Spallanzani, Andrea, Quarà, Virginia, Belli, Carmen, Vaiani, Marta, Curigliano, Giuseppe, Cremolini, Chiara, De Braud, Filippo, Di Bartolomeo, Maria, Zagonel, Vittorina, Lonardi, Sara, Pietrantonio, Filippo
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.04.2021; BMJ Publishing Group
• Series: Original research
• Subjects: Aged; Cancer; Clinical/Translational Cancer Immunotherapy; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - immunology; Colorectal Neoplasms - pathology; Disease Progression; Female; Humans; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Italy; Male; Metastasis; Microsatellite Instability; Neoplasm Metastasis; Population; Progression-Free Survival; Regression analysis; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Tumor Burden - drug effects; Variables; Italy; tumor biomarkers; immunotherapy; gastrointestinal neoplasms
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1136/jitc-2021-002501

BackgroundImmune 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.MethodsThis 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.ResultsWe 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.ConclusionsETS 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.