Plasma Angiogenic Factors as Predictors of the Efficacy of Second-line Chemotherapy Combined with Angiogenesis Inhibitors in Metastatic Colorectal Cancer: Results From the GI-SCREEN CRC-Ukit Study.
Clin Colorectal Cancer
; 23(2): 147-159.e7, 2024 Jun.
Article
in En
| MEDLINE
| ID: mdl-38331650
ABSTRACT
BACKGROUND:
The significance of angiogenic factors as predictors of second-line (2L) chemotherapy efficacy when combined with angiogenesis inhibitors for metastatic colorectal cancer (mCRC) remains unestablished. PATIENTS ANDMETHODS:
In this multicenter prospective observational study, 17 angiogenic factors were analyzed in plasma samples collected at pretreatment and progression stages using a Luminex multiplex assay. Patients who received chemotherapy plus bevacizumab (BEV group), FOLFIRI plus ramucirumab (RAM group), or FOLFIRI plus aflibercept (AFL group) as the 2L treatment were included. Interactions between pretreatment and treatment groups for progression-free survival (PFS), overall survival (OS), and response rate (RR) were assessed using the propensity-score weighted Cox proportional hazards model.RESULTS:
From February 2018 to September 2020, 283 patients were analyzed in the 2L cohort. A strong interaction was observed for PFS between BEV and RAM with HGF, sNeuropilin-1, sVEGFR-1, and sVEGFR-3. Interactions for RR between the BEV and RAM groups were observed for sNeuropilin-1 and sVEGFR-1. Contrarily, OS, PlGF, sVEGFR-1, and sVEGFR-3 differentiated the treatment effect between BEV and AFL. Plasma samples were evaluable for dynamic analysis in 203 patients. At progression, VEGF-A levels significantly decreased in the BEV group and increased in the RAM and AFL groups.CONCLUSION:
The pretreatment plasma sVEGFR-1 and sVEGFR-3 levels could be predictive biomarkers for distinguishing BEV and RAM when combined with chemotherapy in 2L mCRC treatment. Based on the VEGF-A dynamics at progression, selecting RAM or AFL for patients with significantly elevated VEGF-A levels may be a 2L treatment strategy, with BEV considered for the third-line treatment. CLINICAL TRIAL NUMBER UMIN000028616.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Camptothecin
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Colorectal Neoplasms
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Antineoplastic Combined Chemotherapy Protocols
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Leucovorin
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Angiogenesis Inhibitors
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Bevacizumab
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Fluorouracil
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Ramucirumab
Type of study:
Clinical_trials
/
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
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Aged
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Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Clin Colorectal Cancer
Journal subject:
GASTROENTEROLOGIA
/
NEOPLASIAS
Year:
2024
Document type:
Article