preface
The 2024 European Society for Medical Oncology Annual Meeting (2024 ESMO) was held in Barcelona, Spain from September 13 to September 17. At that time, scholars from the field of oncology from all over the world will gather together to share the latest research progress in cancer diagnosis and treatment. On the occasion of this meeting, the latest results of a prospective, multi-center cohort study presided over by Professor Zhang Pin from the Cancer Hospital of the Chinese Academy of Medical Sciences were selected for poster presentation at the conference. The study aims to explore the neoadjuvant treatment option of "anthracene" for triple-negative breast cancer (TNBC) and has made positive progress.
Background:
Anthracyclines in combination with taxanes are the recommended regimens for neoadjuvant chemotherapy for TNBC. Some single-arm or phase II studies have shown that carboplatin plus taxanes (anthracycline) neoadjuvant therapy for TNBC is comparable to or better than anthracycline + taxane regimen, with milder adverse effects, but these studies have small sample sizes and lack survival data. Cell-free DNA (cfDNA) permethylome sequencing (WMS) is currently mainly used for early screening of a variety of cancers, and its use as a biomarker of breast cancer efficacy and prognosis has not been reported.
Research Methods:
This study is a prospective, multicenter cohort study. Patients with stage IIb~IIIc TNBC were selected and given carboplatin AUC 5 q3w or carboplatin AUC 4 q2w in combination with taxane (paclitaxel or nab-paclitaxel or docetaxel standard dose) for 6 cycles of neoadjuvant chemotherapy. Plasma samples were prospectively collected at baseline (T1) and at the end of neoadjuvant chemotherapy (T2). Biomarkers such as chromosome copy number variation (CAFF), fragment size index (FSI) and cfDNA methylation density score (MD) were obtained based on cfDNA WMS detection. Primary endpoint: recurrence-free survival (RFS); Secondary endpoints: overall survival (OS) and exploratory biomarker analysis.
Findings:
A total of 267 patients were enrolled in the study; The median age was 49 years, 156 (58.4%) had stage III, 206 (77.1%) had positive axillary lymph nodes, and 17.2% (46/267) had cN3. A total of 214 patients (80.1%) completed 6 cycles or more of treatment, and 257 patients (96.3%) completed more than 4 cycles of treatment. The most common grade 3/4 chemotherapy adverse reactions were neutropenia (30.0%) and leukopenia (12.0%). Eighty patients (30.0%) had their dose reduced due to adverse reactions, and 3 patients (1.1%) discontinued treatment due to adverse reactions.
In terms of surgery, a total of 263 patients underwent surgery, of which 106 (40.3%) achieved pathologic complete response (pCR, ypT0/isN0) and 33 (12.5%) had only minimal residual disease (ypT1mi/1a/1b N0). At a median follow-up of 36.0 months, the three-year RFS and OS were 77.9% and 87.6%, respectively. Those with pCR had better RFS and OS than those without pCR (RFS 95.5 versus 76.6 percent, respectively; OS was 97.7% vs 81.2%, P <0.001). The 3-year RFS and OS were 83.1% and 91.3%, respectively, and the 3-year RFS and OS of patients with minimal postoperative residual disease were comparable to those of patients with pCR, 80.2% vs 92.3% (P=0.060) and 90.5% vs 97.4% (P=0.247), respectively. The 3-year RFS and OS of patients with ≥3 residual lymph nodes were significantly lower than those with <3 lymph nodes (Log-rank P<0.0001).
In terms of cfDNA testing, 120 plasma samples (64 for T1 and 56 for T2) from 66 patients were included in the WMS analysis. The proportion of FSI-negative patients at T2 in the pCR group was significantly higher than that in the non-pCR group (86.2% vs 59.3%, P=0.034). The RFS of MD-positive patients at T1 was significantly lower than that of MD-negative patients (P=0.028).
Conclusions of the study
This study further confirmed that carboplatin combined with taxanes is an important option for neoadjuvant chemotherapy for TNBC, especially for patients who are not candidates for anthracycline chemotherapy. cfDNA WMS-based biomarkers can provide predictive and prognostic information and are worthy of expanding the sample for further study.
Participation in research centers
Cancer Hospital of Chinese Academy of Medical Sciences (PI)
Beijing Xuanwu Hospital, Capital Medical University
The Affiliated Hospital of Hebei University
Beijing Hospital
Expert Profile
Prof. Pin Zhang
- Chief physician, professor and doctoral supervisor of the Department of Internal Medicine, Cancer Hospital, Chinese Academy of Medical Sciences
- Vice Chairman of the Breast Disease Branch of Beijing Medical Association
- Vice Chairman of the Internal Medicine Professional Committee of the Beijing Society for the Prevention and Treatment of Breast Diseases
- Vice Chairman of the Breast Professional Committee of the Chinese Women Physicians Association
- Vice Chairman of the Breast Cancer Subcommittee of the Chinese Gerontological Society
- Member of the Standing Committee of the Breast Professional Committee of the Chinese Association of Research Hospitals
- Member of the Standing Committee of the Clinical Oncology Committee of the Chinese Association of Women Physicians
- Member of the Standing Committee of the Breast Disease Training Expert Committee of the Chinese Medical Doctor Association
- Member of the Breast Cancer Professional Committee of the Chinese Anti-Cancer Association
- He is a member of the Clinical Chemotherapy Committee of the Chinese Anti-Cancer Association
- He is a member of the Breast Disease Expert Committee of Beijing Medical Doctor Association
Bibliography:
Zhang Pin, et al. 2024 ESMO 333P.
扫码查看WCLC+ESMO大会精彩资讯
Editor: Prof. Pin Zhang
Reviewer: Ryland
Typography: Ryland
Execution: Squid
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