Abstract 181P
Background
Perioperative chemotherapy changes the treatment paradigm in locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. S-1 shows compelling efficacy as a chemotherapeutic backbone. However, the efficacy of S-1-based triplet combination has not been well-established in these patients.
Methods
The trial was a prospective single-arm multi-centered phase II study incorporating 8 cycles of perioperative leucovorin, oxaliplatin, docetaxel and S-1 (LOTS) in patients with ≥cT2 or lymph node-positive non-metastatic gastric/GEJ adenocarcinoma in addition to a curative surgery. The primary endpoint was the treatment response assessed by image- or pathology-defined modalities. Secondary objectives included survivals, toxicities and the predictability of plasma-derived cell-free DNA (cfDNA).
Results
From Jul 2021 to Jan 2024 with a median follow-up time of 11.3 months, a total of 46 patients were enrolled. Patients with clinical ≥T2 or lymph node-positive disease accounted for over 90% of the population. Ninety-eight percent of the patients received the planned curative surgery. Objective response rate by image-based modality of preoperative LOTS was 39%. An above partial tumor regression was observed in 54% of the patients. The toxicities were tolerable, with grade III/IV reactions in neutropenia (28%), diarrhea (24%), nausea (13%) and vomiting (13%). The cfDNA levels were statistically different in responders versus non-responders after preoperative LOTS (2.6 vs 8.6 ng/mL, p=0.0285 by Mann-Whitney test). Table: 181P
| Before PreOP CT | After PreOP CT | |||
| Mandard TRG, n (%) | ||||
| 1 (pCR) | - | 1 | (2.4) | |
| 2 | - | 8 | (19.5) | |
| 3 (pPR) | - | 13 | (31.7) | |
| 4 | - | 17 | (41.5) | |
| 5 (NR) | - | 2 | (4.9) | |
Conclusions
Perioperative LOTS demonstrates reasonable therapeutic efficacy and manageable toxicity in patients with locally advanced gastric or GEJ adenocarcinoma in addition to surgery. Plasma-derived cfDNA levels correspond to treatment response and might provide clues as a predictive biomarker.
Clinical trial identification
NCT04999332.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
1) TTY Biopharm, Taipei, Taiwan; 2) Ministry of Health and Welfare (MOHW110-TDU-B-211-124003), Taipei, Taiwan.
Disclosure
All authors have declared no conflicts of interest.