Abstract 1452P
Background
Our data (ASCO-GI 2017, ASCO 2018, ESMO-ASIA 2018) suggests that apatinib may enhance cytotoxicity by inhibiting cell membrane–bound ABC transporters. POF is effective in TNAGC, as reported in our phase II study (ASCO-GI 2019). In initial designation from a phase I study of apatinib plus POF in TNAGC, apatinib dose level (dl) is between 250 to 750 mg. The maximum tolerated dose (MTD) was not reached, with a response rate of 72.7% and good safety profile (ESMO 2019). In this study, we extended the dl to 850mg.
Methods
This was a phase I single centre study with standard 3+3 design for pts with TNAGC. The primary endpoints are determining dose limiting toxicities (DLT) and MTD. The study included 6 escalating dl of apatinib (250, 375, 500, 625, 750, and 850mg daily) plus POF, consisting 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-haematologic ≥ grade 3 toxicity (except for nausea and vomiting that could be improved with optimal supportive care, escalation of ALP).
Results
23 pts were treated in 6 different dl of apatinib plus POF (3 in each dl, except for 5 in dl 625 mg and 6 in dl 850 mg). Median age was 55 years (range 25-69) with 69.7% male. All pts were evaluated for toxicity; 21 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). One pt (1/6) had DLT at dl 850 mg with herpes in perineum and grade 3 stomatitis. Of 16 evaluable pts, 13 (81.25%) had partial response (PR), 1 had stable disease (SD), 2 had progressive disease (PD). Five evaluable pts in dl 850mg all had PR. Median progression-free survival (PFS) was 10.8m (95%CI 8.1-14.6m). Median overall survival (OS) was not reached. Grade 3 neutropenia, stomatitis, and herpes was observed in 7, 1, and 1 pts. The remaining toxicities were ≤ grade 2. Most frequent toxicities were anaemia (73.91%), hypoalbuminemia (60.87%), and neutropenia (52.17%).
Conclusions
Apatinib can be safely administered up to 850 mg daily plus POF for pts with TNAGC. The dose level is possibly related to the response. Phase II trials with apatinib 750 mg plus POF are ongoing.
Clinical trial identification
NCT03244774.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Jiangsu HengRui Medicine Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.