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
3392 - Post-hoc analysis of the nintedanib exposure-response relationships in the CHIVA trial in advanced ovarian cancer: (a GINECO study)
Presenter: Skerdi HAVIARI
Session: Poster Display session 2
Resources:
Abstract
714 - The feasibility and efficacy of gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian insufficiency in patient with malignant ovarian germ cell tumors
Presenter: Min Kyu Kim
Session: Poster Display session 2
Resources:
Abstract
1753 - Ex vivo cytotoxicity and in vivo antitumor activity of a novel highly selective STAT3 inhibitor YHO-1701 for ovarian and endometrial cancer
Presenter: Kosei Hasegawa
Session: Poster Display session 2
Resources:
Abstract
3739 - Mutational landscapes and tumor mutational burden expression in endometrial cancer
Presenter: Yingli Zhang
Session: Poster Display session 2
Resources:
Abstract
2109 - Clinical features and frequency of mismatch repair protein deficiency in ovarian clear cell and endometrioid carcinoma patients.
Presenter: Kazuhiro Takehara
Session: Poster Display session 2
Resources:
Abstract
4554 - Prospective study evaluating white adipose tissue inflammation and clinicopathologic features in endometrial cancer
Presenter: Lea Moukarzel
Session: Poster Display session 2
Resources:
Abstract
3645 - Cancer-specific survival with or without adjuvant chemotherapy in high-risk stage I endometrial cancer
Presenter: Jenny Ko
Session: Poster Display session 2
Resources:
Abstract
3394 - Pembrolizumab in Patients with MSI-H Advanced Endometrial Cancer from the KEYNOTE-158 Study
Presenter: David Omalley
Session: Poster Display session 2
Resources:
Abstract
3388 - Who drops out of cervical cancer screening? Results from the EDIFICE 6 survey
Presenter: Thibault de La Motte Rouge
Session: Poster Display session 2
Resources:
Abstract
2485 - Identification of a RNA-Seq Based Signature to Improve Prognostic for Uterine Sarcoma
Presenter: Jian-Guo Zhou
Session: Poster Display session 2
Resources:
Abstract