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12.08.2019 | Clinical trial

Exploratory biomarker analysis from a phase II clinical trial of eribulin plus gemcitabine versus paclitaxel plus gemcitabine for HER2-negative metastatic breast cancer patients (KCSG BR13-11)

verfasst von: Ji-Yeon Kim, Eunjin Lee, Kyunghee Park, Seock-Ah Im, Joohyuk Sohn, Keun Seok Lee, Yee Soo Chae, Jee Hyun Kim, Tae-Yong Kim, Kyung Hae Jung, Yeon Hee Park, the Breast Cancer Committee of the Korean Cancer Study Group

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2019

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Abstract

Purpose

We conducted an exploratory biomarker study from a phase II clinical trial of eribulin plus gemcitabine (EG) versus paclitaxel plus gemcitabine (PG) in HER2-negative metastatic breast cancer (BC) patients.

Methods

We performed targeted deep sequencing with a customized cancer gene panel and RNA expression assay. Tumor mutation burden (TMB) and mutation signatures were determined based on genetic alteration in targeted regions. Gene set variation analysis was performed with PanCancer Immune Profiling and PanCancer Pathway Panels. Statistical analyses were conducted to identify the associations between genetic alterations and clinical outcomes.

Results

Of 119 patients, 40 had available biomarker data. Among the 40 patients, 4 supported their post-treatment tissues. In targeted deep sequencing, FAT3 (48%) was the most frequently mutated gene, followed by PKHD1, TP53, GATA3, PARP4, and PIK3CA. In terms of gene expression, low expression of epithelial-mesenchymal transition (EMT) pathway genes was associated with prolonged progression-free survival (PFS) in the EG group, while high expression of the EMT pathway was associated with good prognosis in the PG group. Median TMB was 6.5 (range 2.44–46.34) and there was no relationship between TMB and patient prognosis. Analysis of mutation signatures showed that signatures 3, 20, and 26 were frequently observed in our cohort. Further survival analysis according to mutation signature showed that mutation signature 3, as a homologous recombinant deficiency-related signature, was highly associated with disease progression (hazard ratio (log2 scale) 8.21, 95% confidence interval 2.93–13.48, p = 0.002). Kaplan–Meier plot also showed that BCs with signature 3 had short PFS compared to those without these signatures (median PFS (months) for signature 3 (low vs. high): 17.2 vs. 8.1, p = 0.0026).

Conclusions

Mutation signature 3, found in about 30% of MBCs regardless of hormone receptor status, was associated with short PFS for patients with cytotoxic chemotherapy.

Trial registry

ClinicalTrials.gov number: NCT02263495.

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Titel: Exploratory biomarker analysis from a phase II clinical trial of eribulin plus gemcitabine versus paclitaxel plus gemcitabine for HER2-negative metastatic breast cancer patients (KCSG BR13-11)
verfasst von: Ji-Yeon Kim
Eunjin Lee
Kyunghee Park
Seock-Ah Im
Joohyuk Sohn
Keun Seok Lee
Yee Soo Chae
Jee Hyun Kim
Tae-Yong Kim
Kyung Hae Jung
Yeon Hee Park
the Breast Cancer Committee of the Korean Cancer Study Group
Publikationsdatum: 12.08.2019
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 2/2019
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-019-05400-y

Neu im Fachgebiet Onkologie

25.04.2024 | Nierenkarzinom | Nachrichten

Springer Medizin

Exploratory biomarker analysis from a phase II clinical trial of eribulin plus gemcitabine versus paclitaxel plus gemcitabine for HER2-negative metastatic breast cancer patients (KCSG BR13-11)

Abstract

Purpose

Methods

Results

Conclusions

Trial registry

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Trial registry

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