Abstract 1257P
Background
The phase I SYLT 007 study (ESMO 2020) suggested that the maximum tolerated dose (MTD) of apatinib did not reach with apatinib up to 850 mg daily plus POF in TNAGC. We present results of SYLT 007 in TNAGC after 2 additional years of follow-up (cutoff: Mar 30, 2022).
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 MTD. The study included 6 escalating dl of apatinib (250, 375, 500, 625, 750, and 850mg 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 ALP).
Results
Twenty-three 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 69.6% male. One pts (1/6) had DLT at dl 850 mg with herpes in perineum and grade 3 stomatitis. Of 16 evaluable pts, 13 (81.25%) were PR, 1 was SD, 2 was PD). Median PFS was 10.6m (95%CI 6.91-14.29m). Median OS was 18.667m (95%CI 10.443-26.891m). Most frequent of toxicity were anemia (82.6%), hypoalbuminemia (73.9%), and neutropenia (69.6%). Interestingly, patients with the high-dose apatinib (625, 750, and 850mg daily) plus POF were associated with better ORR (90.9% 10/11), DCR (100% 11/11), and longer mPFS (10.67m 95%CI 10.16-11.18m) and mOS (19.9m 95%CI 14.75-25.05m). Of the 5 pts who survived for more than 30 months, 2 accepted the re-challenge of the original protocol (625mg, 850mg respectively), 1 received immune checkpoint inhibitor combined with chemotherapy (750mg), 1 underwent radical surgery and is now free of recurrence (850mg), 1 received S-1 plus apatinib maintenance (850mg). Five evaluable pts in dl 850mg were all PR and 3 of them survived more than 30 months.
Conclusions
High-dose apatinib plus POF had encouraging antitumor activity with manageable safety profile in TNAGC.
Clinical trial identification
NCT03244774.
Editorial acknowledgement
Legal entity responsible for the study
Rongbo Lin.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.