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Multicenter Study
. 2021 Apr;9(4):e002501.
doi: 10.1136/jitc-2021-002501.

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

Giovanni Fucà  1 , Francesca Corti  1 , Margherita Ambrosini  1 , Rossana Intini  2 , Massimiliano Salati  3 , Elisabetta Fenocchio  4 , Paolo Manca  1 , Chiara Manai  2 , Francesca Daniel  2 , Alessandra Raimondi  1 , Federica Morano  1 , Salvatore Corallo  1 , Michele Prisciandaro  1 , Andrea Spallanzani  3 , Virginia Quarà  4 , Carmen Belli  5 , Marta Vaiani  6 , Giuseppe Curigliano  5   7 , Chiara Cremolini  8   9 , Filippo De Braud  1   7 , Maria Di Bartolomeo  1 , Vittorina Zagonel  2 , Sara Lonardi  2 , Filippo Pietrantonio  10
Affiliations
Multicenter Study

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

Giovanni Fucà et al. J Immunother Cancer. 2021 Apr.

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.

Keywords: gastrointestinal neoplasms; immunotherapy; tumor biomarkers.

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Conflict of interest statement

Competing interests: GC reports the following competing interests outside the present work: advisory board member of Novartis, Roche, Lilly, Daichi-Sankyo, Astra Zeneca, Veracyte and Genomic Health; scientific advisor for Ellipsis. All the remaining authors declared no conflict of interest.

Figures

Figure 1
Figure 1
Kaplan-Meier estimates for OS (panel A) and PFS (panel B) according to ETS. ETS, early tumor shrinkage; OS, overall survival; PFS, progression-free survival.
Figure 2
Figure 2
Kaplan-Meier estimates for OS (A, C) and PFS (B, D) according to ETS and the type of ICI regimen. ETS, early tumor shrinkage; OS, overall survival; PFS, progression-free survival.
Figure 3
Figure 3
Kaplan-Meier estimates for OS (A) and PFS (B) according to DoR. DoR, depth of response; OS, overall survival; minPR, minor partial response; PFS, progression-free survival; VGPR, very good partial response.
See this image and copyright information in PMC

Comment in

  • Letter to the Editor from Colle et al.
    Colle R, Andre T, Menu Y. Colle R, et al. J Immunother Cancer. 2021 Jun;9(6):e002997. doi: 10.1136/jitc-2021-002997. J Immunother Cancer. 2021. PMID: 34162716 Free PMC article.

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