Background The correlations between circulating tumour DNA (ctDNA)-derived genomic markers and treatment response and survival outcome in Chinese patients with advanced breast cancer (ABC) have not been extensively characterized. Methods Blood samples from 141 ABC patients who underwent first-line standard treatment in Peking University Cancer Hospital were collected. A next-generation sequencing based liquid biopsy assay (PredicineCARE) was used to detect somatic mutations and copy number variations (CNVs) in ctDNA. A subset of matched blood samples and tumour tissue biopsies were compared to evaluate the concordance. Results Overall, TP53 (44.0%) and PIK3CA (28.4%) were the top two altered genes. Frequent CNVs included amplifications of ERBB2 (24.8%) and FGFR1 (8.5%) and deletions of CDKN2A (3.5%). PIK3CA/TP53 and FGFR1/2/3 variants were associated with drug resistance in hormone receptor-positive (HR +) and human epidermal growth factor receptor 2-positive (HER2 +) patients. The comparison of genomic variants across matched tumour tissue and ctDNA samples revealed a moderate to high concordance that was gene dependent. Triple-negative breast cancer (TNBC) patients harbouring TP53 or PIK3CA alterations had a shorter overall survival than those without corresponding mutations (P = 0.03 and 0.008). A high ctDNA fraction was correlated with a shorter progression-free survival (PFS) (P = 0.005) in TNBC patients. High blood-based tumor mutation burden (bTMB) was associated with a shorter PFS for HER2 + and TNBC patients (P = 0.009 and 0.05). Moreover, disease monitoring revealed several acquired genomic variants such as ESR1 mutations, CDKN2A deletions, and FGFR1 amplifications. Conclusions This study revealed the molecular profiles of Chinese patients with ABC and the clinical validity of ctDNA-derived markers, including the ctDNA fraction and bTMB, for predicting treatment response, prognosis, and disease progression. Trial registration: ClinicalTrials.gov ID: NCT03792529. Registered January 3rd 2019, https://clinicaltrials.gov/ct2/show/NCT03792529.
Purpose To evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) heavily pretreated with anthracycline and taxanes. Methods In this single-arm, phase II study, patients with HER2-negative MBC previously treated with anthracycline and taxanes as second- to fifth chemotherapy received PLD (Duomeisu®, generic doxorubicin hydrochloride liposome) 40 mg/m2 every 4 weeks until disease progression, unacceptable toxicity, or completion of six cycles. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), and safety. Results Of 44 enrolled patients (median age, 53.5 years; range, 34–69), 41 and 36 were evaluable for safety and efficacy, respectively. In total, 59.1% (26/44) of patients had ≥ 3 metastatic sites, 86.4% (38/44) had visceral disease, and 63.6% (28/44) had liver metastases. Median PFS was 3.7 months (95% confidence interval [CI] 3.3–4.1) and median OS was 15.0 months (95% CI 12.1–17.9). ORR, DCR, and CBR were 16.7%, 63.9%, and 36.1%, respectively. The most common adverse events (AEs) were leukopenia (53.7%), fatigue (46.3%), and neutropenia (41.5%), with no grade 4/5 AEs. The most common grade 3 AEs were neutropenia (7.3%) and fatigue (4.9%). Patients experienced palmar-plantar-erythrodysesthesia (24.4%, 2.4% grade 3), stomatitis (19.5%, 7.3% grade 2), and alopecia (7.3%). One patient displayed a left ventricular ejection fraction decline of 11.4% from baseline after five cycles of PLD therapy. Conclusion PLD (Duomeisu®) 40 mg/m2 every 4 weeks was effective and well-tolerated in patients with HER2-negative MBC heavily pretreated with anthracycline and taxanes, revealing a potentially viable treatment option for this population. Trial registration Chinese Clinical Trial Registry: ChiCTR1900022568.
IntroductionEribulin is currently recommended for the treatment of patients with metastatic breast cancer (MBC) pre‐treated with taxanes and anthracyclines. The aim of the present study was to evaluate the effectiveness and safety of eribulin and its impact on health‐related quality of life in heavily pre‐treated patients with MBC.MethodsData from MBC patients who had received eribulin‐based therapy at Beijing Cancer Hospital between January 2020 and July 2022 were analyzed retrospectively. Progression‐free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), adverse effects (AEs) and health‐related quality of life (HRQoL) were assessed.ResultsData from 118 patients who had received eribulin to treat MBC were included. Median PFS was 4.2 months and median OS had not been reached. The ORR was 13.6% (16/118) and DCR was 75.4% (89/118). The median PFS in patients who received eribulin in second‐line (26/118), third‐line (29/118), or fourth‐line or later (63/118) was 4.5, 4.2, and 3.9 months, respectively. The median OS in patients who received eribulin in third‐ or later line (n = 92) was 14.1 months. Patients who received eribulin combination therapy had a significantly longer median PFS compared with those who received eribulin monotherapy (4.5 vs. 3.4 months, p = 0.007) and there was a trend towards a longer median OS (not reached vs. 12.1 months). The most common grade 3–4 adverse events were neutropenia (22.9%), leukocytopenia (13.6%) and asthenia/fatigue (8.5%), without significant differences in safety between eribulin monotherapy and combination therapy. Quality of life was similar in patients who received eribulin monotherapy and combination therapy, except for cognitive function and nausea and vomiting symptoms, which were better with combination therapy.ConclusionsThe present study suggests that eribulin‐based therapy is an effective treatment option and well tolerated for heavily pre‐treated patients with MBC. Eribulin combination therapy might improve PFS and HRQoL compared with eribulin monotherapy.
Background: The differential mutation landscape between ethnics is more comparable when using the identical detecting platform.We explored the differences in genomic landscape of patients with hormone-receptor positive (HR+), HER2-negative MBC of first recurrence or Stage IV at diagnosis from the United States (US) and China (CN).Methods: Twenty-seven US patients and 65 CN patients had circulating tumor DNA (ctDNA) sequencing from plasma using the harmonized CLIA-certified, 152-gene PredicineCareTM liquid biopsy assay. Clinical outcomes were correlated with ctDNA variants. Progression-free survival (PFS) and overall survival analysis was performed for patients and compared using log-rank test. Results: Mutations were detected in 23 of 27 (85%) US patients and 54 of 65 (83%) CN patients. The most common mutations detected included TP53, PIK3CA, CDH1, AKT1, ESR1, and BRCA2 in both US and CN patients. AKT1(18.5% vs. 3.1%, P = 0.008) and CDH1 mutations were more frequent in the US population (18.5% vs. 1.5%, P = 0.021), and gain of FGFR1 was more common in the CN cohort (7.4% vs. 24.6%, P = 0.048). PTEN deletion (5.7 months vs. 13.2 months, P = 0.03) and ESR1 alterations (9.0 months vs. 13.2 months, P = 0.02) were associated with significantly shorter PFS in CN cohort. Conclusions: To our knowledge, this is the first real world study using a single harmonized ctDNA assay to profile plasma samples of patients from the US and CN. Differential prevalence of the mutations with therapeutic potential were found between US and CN.
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