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
1058 - Assessment of CPS+EG, Neo-Bioscore and modified Neo-Bioscore in breast cancer patients treated with preoperative systemic therapy: a multicenter cohort study
Presenter: LING XU
Session: Poster Display session 2
Resources:
Abstract
1156 - The concordance of treatment decision guided by Oncotype and the PREDICT tool in early stage breast cancer
Presenter: Hadar Goldvaser
Session: Poster Display session 2
Resources:
Abstract
3447 - Influence of first treatment delay on survival among breast cancer subtypes
Presenter: Irene Zarcos Pedrinaci
Session: Poster Display session 2
Resources:
Abstract
3505 - Clinical features of early-stage (I-III) triple-negative breast cancer (TNBC) patients with tumors exhibiting low-overall change in molecular profile after neoadjuvant therapy.
Presenter: Nour Abuhadra
Session: Poster Display session 2
Resources:
Abstract
5442 - Meta-analysis in HER2+ early breast cancer therapies and cost-effectiveness in a Brazilian perspective
Presenter: Marcos Magalhaes
Session: Poster Display session 2
Resources:
Abstract
1570 - Anti-mullerian hormone (AMH) levels and antral follicle counts (AFC) may predict ovarian reserves before systemic chemotherapy (SC) in women with breast cancer(BC); a prospective clinical study
Presenter: Cetin Ordu
Session: Poster Display session 2
Resources:
Abstract
2698 - Prognosis of selected triple negative apocrine breast cancer patients who did not receive adjuvant chemotherapy.
Presenter: Giuseppe Cancello
Session: Poster Display session 2
Resources:
Abstract
3104 - Novel Blood Based Circulating Tumor Cell Biomarker For Breast Cancer Detection
Presenter: Chun-Yu Liu
Session: Poster Display session 2
Resources:
Abstract
4631 - Multi-Gene Prognostic Signatures and Prediction of Pathological Complete Response of ER-Positive HER2-Negative Breast Cancer Patients to Neo-Adjuvant Chemotherapy
Presenter: Claudia Mazo
Session: Poster Display session 2
Resources:
Abstract
4632 - Impact of menopause status on breast cancer outcomes and amenorrhea incidence during adjuvant tailored dose dense chemotherapy
Presenter: Andri Papakonstantinou
Session: Poster Display session 2
Resources:
Abstract