Prognostic impact of early tumor shrinkage and depth of response in patients with microsatellite instability-high metastatic colorectal cancer receiving immune checkpoint inhibitors.
J Immunother Cancer
; 9(4)2021 04.
Article
de En
| MEDLINE
| ID: mdl-33849927
ABSTRACT
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.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tumeurs colorectales
/
Charge tumorale
/
Instabilité des microsatellites
/
Inhibiteurs de points de contrôle immunitaires
Type d'étude:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limites:
Aged
/
Female
/
Humans
/
Male
Pays/Région comme sujet:
Europa
Langue:
En
Journal:
J Immunother Cancer
Année:
2021
Type de document:
Article
Pays d'affiliation:
Italie