Phase 2 study of anlotinib combined with taxanes and lobaplatin in the neoadjuvant treatment of triple-negative breast cancer: Efficacy, safety and biomarker analysis
Journal of Clinical Oncology
; 40(16), 2022.
Article
in English
| EMBASE | ID: covidwho-2009574
ABSTRACT
Background:
Pathological complete response (pCR) is associated with improved prognosis in triple-negative breast cancer (TNBC). Anlotinib, a novel multi-target tyrosine kinase inhibitor that effectively inhibits VEGFR, FGFR, c-KIT, c-MET, and RET, monotherapy has been proven effective in HER-2 negative metastatic breast cancer, but its efficacy in early-stage TNBC is unknown. This phase 2 study aims to evaluate the efficacy and safety of adding anlotinib to neoadjuvant chemotherapy in patients (pts) with primary TNBC.Methods:
Pts with clinical stage II/III TNBC were to be treated with 5 cycles of anlotinib (12mg, d1-14, q3w) plus 6 cycles of taxanes (docetaxel 75 mg/m2 or nab-paclitaxel 260 mg/m2, d1, q3w) and lobaplatin (30 mg/m2, d1, q3w), followed by surgery. The primary endpoint was the total pCR (tpCR;ypT0/is ypN0). A Simon's two-stage optimum design was used, and > 5 of 11 pts were required to achieve tpCR in the first stage, with a pre-specified tpCR rate of 54.5% before proceeding to the second stage. A total of 31 participants was required for the study.Results:
Six out of 11 pts achieved tpCR in the first stage, reaching the threshold for the second stage. From Jan 2021 to Jan 2022, a total of 22 pts were enrolled and 12 received surgery after the completion of neoadjuvant therapy, but a total of 2 pts withdrew from the study due to the COVID-19 pandemic or serious adverse events. Of the 22 eligible pts, the median age was 49 years (range, 29-64), 64% were postmenopausal, and 73% were nodal involved. At the time of surgery, 58.3% (7/12) achieved tpCR. Of the 9 pts with the node-positive disease at diagnosis, 88.9% (8/9) became ypN0. The results of FUSCC TNBC classification (IHC-based) revealed the tpCR rates were 57.1% (4/7), 100% (3/3), and 0% (0/2) for BLIS subtype, IM subtype and LAR/unknown subtypes, respectively. Biomarker analysis showed the tpCR rates were 100% (3/3) and 100% (4/4) in patients with gBRCA1 mutation and MYC amplification, respectively. The most common grade 3 or 4 treatment-related adverse events were leucopenia (6/22, 27%), neutropenia (6/22, 27%), anemia (5/22, 23%), decreased appetite (5/22, 23%), hypertension (2/22, 9%), ALT increased (1/22, 5%) and oral mucositis (1/22, 5%). No treatment-related deaths occurred. The trial is ongoing.Conclusions:
The addition of anlotinib to neoadjuvant chemotherapy showed manageable toxicity and promising antitumor activity for patients with early-stage TNBC.
biological marker; catequentinib; docetaxel; endogenous compound; lobaplatin; paclitaxel; adult; anemia; antineoplastic activity; cancer classification; cancer patient; cancer staging; cancer surgery; clinical article; clinical trial; comparative effectiveness; conference abstract; controlled study; coronavirus disease 2019; decreased appetite; drug combination; drug efficacy; drug safety; drug therapy; female; gene amplification; genetic marker; human; human tissue; hypertension; immunohistochemistry; leukopenia; middle aged; neoadjuvant chemotherapy; neutropenia; oncogene myc; oral mucositis; pandemic; phase 2 clinical trial; remission; triple negative breast cancer
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
Journal of Clinical Oncology
Year:
2022
Document Type:
Article
Similar
MEDLINE
...
LILACS
LIS