Predicting Benefit From FOLFOXIRI Plus Bevacizumab in Patients With Metastatic Colorectal Cancer.

Autor:	Bond MJG; Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., van Smeden M; Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Degeling K; Cancer Health Services Research, Centre for Cancer Research, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia.; Cancer Health Services Research, Centre for Health Policy, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia., Cremolini C; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, University Hospital of Pisa, Pisa, Italy.; Department of Oncology, University Hospital of Pisa, Pisa, Italy., Schmoll HJ; Department of Clinical Hematology-Oncology, University Clinic Halle, Martin Luther University, Halle, Germany., Antoniotti C; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, University Hospital of Pisa, Pisa, Italy.; Department of Oncology, University Hospital of Pisa, Pisa, Italy., Lonardi S; Department of Oncology, Veneto Institute of Oncology IOV -IRCCS, Padua, Italy., Murgioni S; Department of Oncology, Veneto Institute of Oncology IOV -IRCCS, Padua, Italy., Rossini D; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, University Hospital of Pisa, Pisa, Italy.; Department of Oncology, University Hospital of Pisa, Pisa, Italy.; Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy., Ibach S; X-act Cologne Clinical Research GmbH, Cologne, Germany., Koopman M; Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Swijnenburg RJ; Department of Surgical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands., Punt CJA; Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., May AM; Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Kwakman JJM; Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.; Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands.
Jazyk:	angličtina
Zdroj:	JCO clinical cancer informatics [JCO Clin Cancer Inform] 2024 Jul; Vol. 8, pp. e2400037.
DOI:	10.1200/CCI.24.00037
Abstrakt:	Purpose: Patient outcomes may differ from randomized trial averages. We aimed to predict benefit from FOLFOXIRI versus infusional fluorouracil, leucovorin, and oxaliplatin/fluorouracil, leucovorin, and irinotecan (FOLFOX/FOLFIRI), both plus bevacizumab, in patients with metastatic colorectal cancer (mCRC). Methods: A Cox model with prespecified clinical, molecular, and laboratory variables was developed in 639 patients from the TRIBE2 trial for predicting 2-year mortality. Data from the CHARTA (n = 232), TRIBE1 (n = 504), and CAIRO5 (liver-only mCRC, n = 287) trials were used for external validation and heterogeneity of treatment effects (HTE) analysis. This involves categorizing patients into risk groups and assessing treatment effects across these groups. Performance was assessed by the C-index and calibration plots. The C-for-benefit was calculated to assess evidence for HTE. The c-for-benefit is specifically designed for HTE analysis. Like the commonly known c-statistic, it summarizes the discrimination of a model. Values over 0.5 indicate evidence for HTE. Results: In TRIBE2, the overoptimism-corrected C-index was 0.66 (95% CI, 0.63 to 0.69). At external validation, the C-index was 0.69 (95% CI, 0.64 to 0.75), 0.68 (95% CI, 0.64 to 0.72), and 0.65 (95% CI, 0.65 to 0.66), in CHARTA, TRIBE1, and CAIRO5, respectively. Calibration plots indicated slight underestimation of mortality. The c-for-benefit indicated evidence for HTE in CHARTA (0.56, 95% CI, 0.48 to 0.65), but not in TRIBE1 (0.49, 95% CI, 0.44 to 0.55) and CAIRO5 (0.40, 95% CI, 0.32 to 0.48). Conclusion: Although 2-year mortality could be reasonably estimated, the HTE analysis showed that clinically available variables did not reliably identify which patients with mCRC benefit from FOLFOXIRI versus FOLFOX/FOLFIRI, both plus bevacizumab, across the three studies.
Databáze:	MEDLINE
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