European journal of cancer (Oxford, England : 1990) · 2025
Molecularly directed therapy in cancers of unknown primary: A systematic review and meta-analysis.
СтатьяСистематический обзорМетаанализНазвание и аннотация: Перевод в очереди
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Labaki Chris, Eid Marc, Bakouny Ziad, Hobeika Charbel, Chehade Razane El Hajj, Chebel Roy, Boussios Stergios, Anthony Greco F, Pavlidis Nicholas, Rassy Elie
Аннотация
BACKGROUND: Cancers of unknown primary (CUP) are associated with a high mortality rate, with limited therapeutic options available and platinum-based chemotherapy recommended as standard of care. Over the past decade, molecularly guided approaches aiming to adapt treatment strategies in patients with CUP based on predicted site of origin (site-specific approach) or genomic characteristics (tissue-agnostic approach) have been explored in clinical studies, with heterogenous findings identified.
METHODS: PubMed/MEDLINE, Scopus, Web of Science, Embase, the Cochrane Library, and conference abstracts of American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) meetings were searched from inception until October 2024, for clinical studies that assessed molecularly directed therapies (MDT) in the management of patients with CUP, as compared to empiric treatment. A meta-analysis using a random-effects model and the inverse variance method was conducted, with a subgroup analysis by study design (randomized versus non-randomized). The primary endpoint was overall survival (OS), and the secondary endpoint was progression-free survival (PFS).
RESULTS: Six studies encompassing 1644 patients were included, of which 4 randomized controlled trials. A significant improvement of OS in patients with CUP treated with MDT versus empiric therapy was identified (HR: 0.75, 95 %CI: 0.62-0.91), with consistent results seen across randomized (HR: 0.86, 95 %CI: 0.73-1.01) and non-randomized (HR: 0.50, 95 %CI: 0.26-0.96). Similarly, PFS was significantly improved with MDT, as compared to empiric treatment (HR: 0.79, 95 %CI: 0.67-0.94).
CONCLUSION: The use of MDT is associated with improved survival outcomes among patients with CUP. These findings provide evidence that support the role of MDT as a potential novel standard of care in CUP treatment.
METHODS: PubMed/MEDLINE, Scopus, Web of Science, Embase, the Cochrane Library, and conference abstracts of American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) meetings were searched from inception until October 2024, for clinical studies that assessed molecularly directed therapies (MDT) in the management of patients with CUP, as compared to empiric treatment. A meta-analysis using a random-effects model and the inverse variance method was conducted, with a subgroup analysis by study design (randomized versus non-randomized). The primary endpoint was overall survival (OS), and the secondary endpoint was progression-free survival (PFS).
RESULTS: Six studies encompassing 1644 patients were included, of which 4 randomized controlled trials. A significant improvement of OS in patients with CUP treated with MDT versus empiric therapy was identified (HR: 0.75, 95 %CI: 0.62-0.91), with consistent results seen across randomized (HR: 0.86, 95 %CI: 0.73-1.01) and non-randomized (HR: 0.50, 95 %CI: 0.26-0.96). Similarly, PFS was significantly improved with MDT, as compared to empiric treatment (HR: 0.79, 95 %CI: 0.67-0.94).
CONCLUSION: The use of MDT is associated with improved survival outcomes among patients with CUP. These findings provide evidence that support the role of MDT as a potential novel standard of care in CUP treatment.