E-viri
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Obermayr, Eva; Mohr, Thomas; Schuster, Eva; Braicu, Elena Ioana; Taube, Eliane; Sehouli, Jalid; Vergote, Ignace; Pujade‐Lauraine, Eric; Ray‐Coquard, Isabelle; Harter, Philipp; Wimberger, Pauline; Joly‐Lobbedez, Florence; Mahner, Sven; Moll, Ute Martha; Concin, Nicole; Zeillinger, Robert
International journal of cancer, 15 September 2024, Letnik: 155, Številka: 6Journal Article
Disease progression is a major problem in ovarian cancer. There are very few treatment options for patients with platinum‐resistant ovarian cancer (PROC), and therefore, these patients have a particularly poor prognosis. The aim of the present study was to identify markers for monitoring the response of 123 PROC patients enrolled in the Phase I/II GANNET53 clinical trial, which evaluated the efficacy of Ganetespib in combination with standard chemotherapy versus standard chemotherapy alone. In total, 474 blood samples were collected, comprising baseline samples taken before the first administration of the study drugs and serial samples taken during treatment until further disease progression (PD). After microfluidic enrichment, 27 gene transcripts were analyzed using quantitative polymerase chain reaction and their utility for disease monitoring was evaluated. At baseline, ERCC1 was associated with an increased risk of PD (hazard ratio HR 1.75, 95% confidence interval CI: 1.20–2.55; p = 0.005), while baseline CDH1 and ESR1 may have a risk‐reducing effect (CDH1 HR 0.66, 95% CI: 0.46–0.96; p = 0.024; ESR1 HR 0.58, 95% CI: 0.39–0.86; p = 0.002). ERCC1 was observed significantly more often (72.7% vs. 53.9%; p = 0.032) and ESR1 significantly less frequently (59.1% vs. 78.3%; p = 0.018) in blood samples taken at radiologically confirmed PD than at controlled disease. At any time during treatment, ERCC1‐presence and ESR1‐absence were associated with short PFS and with higher odds of PD within 6 months (odds ratio 12.77, 95% CI: 4.08–39.97; p < 0.001). Our study demonstrates the clinical relevance of ESR1 and ERCC1 and may encourage the analysis of liquid biopsy samples for the management of PROC patients. What's new? Treatment options for patients with platinum‐resistant ovarian cancer (PROC) are limited, leaving these patients highly vulnerable to disease progression. With the possibility of serial testing to monitor therapeutic response, however, it may now be possible to predict treatment outcomes in PROC patients using liquid biopsy (LB). Here, the authors applied a molecular LB approach in PROC patients with recurring disease and found that ESR1 is a predictive marker for lengthened progression‐free survival. Meanwhile, ERCC1 was associated with disease progression and short survival. The discovery of a prognostic role for ESR1 offers new insight into the biology and treatment of PROC.
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Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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