Abstract 4805
Background
Apatinib, is a novel, small molecule, selective VEGFR-2 TKI and is approved in China as third-line treatment for patients with AGC. Preclinical and clinical data suggests that apatinib may enhance the chemotherapeutic drugs cytotoxicity by inhibiting cell membrane–bound ATP-binding cassette transporters.POF is effective in pts with TNAGC reported in our phase II study. We evaluated the safety and efficacy of apatinib plus POF in TNAGC.
Methods
This was a phase I single center study with standard 3 + 3 design for pts with TNAGC. The primary endpoints are determining dose limiting toxicities (DLT) and maximum tolerated dose (MTD). Secondary endpoints include overall survival (OS), progression free survival (PFS), response rate (RR), and quality of life (QOL). Initial plan was to enroll pts in 5 escalating dose levels of apatinib (250/375/500/625/750mg daily) plus POF, consisted of paclitaxel 135 mg/m2, followed by mFOLFOX6 omitted 5-Fu bolus, every 14 days repeated. Eligible pts had ECOG PS 0-1, age 18-70, and adequate organ function. DLT was any treatment-related hematologic ≥ grade 4 toxicity (except for neutropenia lasting for ≤ 5 days), or non-hematologic ≥ grade 3 toxicity (except for nausea and vomiting that could be improved with optimal supportive care, escalation of alkaline phosphatase).
Results
17 pts were treated in 5 different dl of apatinib plus POF (3 in each dl, except for 5 in dl 625 mg). Median age was 55 years (range 25-69) with 76.5% male. All pts were evaluated for toxicity, but only 15 were evaluable for DLT. 2 pts in dl 625mg were replaced as they came off of study within 28 days (1 due to poor adherence to take apatinib as prescribed, 1 due to concealing his prior chemotherapy). Zero DLTs were observed at all dl. Only 3 pts had grade 3 neutropenia. The rest of toxicities were ≤ grade 2. Most frequent of toxicity were anemia (64.71%), hypoalbuminemia (58.82%), and neutropenia (47.06%). 11 pts were evaluable for response (8 PR [72.73%], 1 SD, 2 PD).5 pts have been on treatment > 6 months.
Conclusions
Apatinib can be safely administered up to 750 mg daily combined with POF for pts with TNAGC.Phase II will begin after phase I completion and will evaluate efficacy of apatinib 750 mg plus POF.
Clinical trial identification
NCT03244774; Release date: August 10, 2017.
Editorial acknowledgement
Legal entity responsible for the study
Rongbo Lin.
Funding
Jiangsu HengRui Medicine Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5612 - Evaluation of germ line mutational status among women with triple-negative breast cancer in Russia
Presenter: Elena Shagimardanova
Session: Poster Display session 2
Resources:
Abstract
4142 - Association of derived neutrophil-to-lymphocyte ratio (dNLR) with pathological complete response (pCR) after neoadjuvant chemotherapy (CT)
Presenter: Alberto Ocaña
Session: Poster Display session 2
Resources:
Abstract
1733 - Competing nomogram for late-period breast cancer-specific death in patients with early-stage hormone receptor-positive breast cancer
Presenter: Jianfei Fu
Session: Poster Display session 2
Resources:
Abstract
1978 - A Nomogram to Predict Pathologic Complete Response of Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Based on Simple Blood Indicators
Presenter: Fanrong Zhang
Session: Poster Display session 2
Resources:
Abstract
3062 - Identification of GSTP1 transferred by extracellular vesicles responsible for adriamycin-resistance in breast cancer cells
Presenter: Sujin Yang
Session: Poster Display session 2
Resources:
Abstract
5274 - Expression of X-linked Inhibitor of Apoptosis Protein (XIAP) and its Association with Clinicopathological Parameters in Invasive Breast Cancers
Presenter: Gayathri Devi
Session: Poster Display session 2
Resources:
Abstract
1324 - The prognostic significance of preoperative tumor marker (CEA, CA15-3) elevation in breast cancer patients
Presenter: Soo Youn Bae
Session: Poster Display session 2
Resources:
Abstract
4877 - Correlation of clinical and pathological features with the tumour microenvironment in DCIS. An institutional experience
Presenter: Ann Eapen
Session: Poster Display session 2
Resources:
Abstract
2471 - Correlation between radiologic complete response (rCR) in contrast-enhanced magnetic resonance imaging (CE-MRI) after neoadjuvant chemotherapy for early breast cancer and pathologic complete response and their impact in recurrence-free survival
Presenter: Ariadna Gasol Cudos
Session: Poster Display session 2
Resources:
Abstract
2632 - Ring-like uptake appearance on dedicated breast positron emission tomography before chemotherapy predicts outcome of neoadjuvant chemotherapy in breast cancer
Presenter: Norio Masumoto
Session: Poster Display session 2
Resources:
Abstract