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

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.

• Authors: Giovanni Fucà, Francesca Corti, Margherita Ambrosini, Rossana Intini, Massimiliano Salati, Elisabetta Fenocchio, Paolo Manca, Chiara Manai, Francesca Daniel, Alessandra Raimondi, Federica Morano, Salvatore Corallo, Michele Prisciandaro, Andrea Spallanzani, Virginia Quarà, Carmen Belli, Marta Vaiani, Giuseppe Curigliano, Chiara Cremolini, Filippo De Braud, Maria Di Bartolomeo, Vittorina Zagonel, Sara Lonardi, Filippo Pietrantonio
• Journal: Journal for immunotherapy of cancer (J Immunother Cancer) Vol. 9 Issue 4 (04 2021) ISSN: 2051-1426 [Electronic] England
• PMID: 33849927 (Publication Type: Journal Article, Multicenter Study)
• Copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Immune Checkpoint Inhibitors

Topics

• Aged
• Colorectal Neoplasms (drug therapy, genetics, immunology, pathology)
• Disease Progression
• Female
• Humans
• Immune Checkpoint Inhibitors (adverse effects, therapeutic use)
• Italy
• Male
• Microsatellite Instability
• Neoplasm Metastasis
• Progression-Free Survival
• Retrospective Studies
• Risk Assessment
• Risk Factors
• Time Factors
• Tumor Burden (drug effects)