The prognosis of locally advanced gastric cancer is poor, even if all known surgical interventions are done. To improve survival, different treatment strategies adjunctive to surgery have been developed. Since the FLOT4-AIO trial was announced, perioperative FLOT (periop-FLOT) is the new standard of care for locally advanced gastric and gastroesophageal junction (LAG/GEJ) cancers. As trials are conducted on well-selected patients, daily clinical practices and the results may differ. We aimed to analyze the tolerability, pathological response rate, and the role of an adjuvant phase of periop-FLOT.

We performed a retrospective study of LAG/GEJ cancers undergoing periop-FLOT during the last two years. The FLOT regimen was applied as in the FLOT4-AIO trial. Pathological tumor regression grade was done according to Modified Ryan Scheme (TRG0: complete response, TRG1: near-complete response, TRG2: partial response, TRG3: poor/no response) and DFS analysis was estimated by Kaplan-Meier method with SPSS.

Fifty-nine pts with LAG/GEJ cancers commenced on periop-FLOT. Demographics: male n=43 (73%), median age 63 (range;34-85), performance status; PS0 n=29 (49%), PS1 n=20 (34%), PS2 n=10 (17%). Tumor location gastric n=38 (64%), GEJ n=21 (36%). All of the pts were cT3/T4, and 55 (93%) were cN+. 53 pts (90%) received ≥4 cycles of neoadj-FLOT. 45 (76%) pts underwent curative surgery, and 40 (89%) of them had D1 lymphadenectomy. R0 resection was achieved in 44 pts (75%). TRG0 n=5 (8%), TRG1 n=9 (15%), TRG2 n=5 (8%) and TRG3 n=26 (44%) were reached, and 22 pts (37%) were detected as ypN0. 30 pts (51%) started adj-FLOT and 26 pts (44%) completed all cycles. The median follow-up was 11 months (range 4–27), with a median DFS of 21.8 months (95% CI 18.9–24.9), and 9 of 45 pts (20%) relapsed. Significant differences in DFS between pts who received adj-FLOT (25.4 months, 95% CI 23.1–27) compared with no-adjuvant (13.6 months, 95% CI 10.2–16.9) were found (p=0.001), and also among ypN0 (26 months, 95% CI 24-28.1) compared with ypN+ (15.6 months, 95% CI 12.4-18.9) (p=0.006). No effect of TRG's on DFS were detected (p>0,05). The median OS not reached. 56 pts (95%) had at least one any grade toxicity. Dose reduction was performed in 3 pts (5%). The most common grade 3/4 toxicities were neutropenia (n=11;19%) and neutropenic fever (n=7;12%) although we prescribed primary prophylactic G-CSF. Two toxic deaths occurred (3%) during the neoadjuvant period. Compared with the FLOT4-AIO trial, although our pts had a higher PS, they had similar rates of dose reduction (5% vs 6%), completing neoadjuvant (90% vs 90%) and adjuvant (44% vs 46%) treatments. R0 (75% vs 85%) and D2 (11% vs 92%) resection, ypN0 (37% vs 49%) and pCR rates (8% vs 16%) were lower in our pts, due to higher initial clinical stages.

This is an interim analysis of our experience. In our study, periop-FLOT was well tolerated although the pts had a higher PS. Due to the high initial clinical stages, pathological response rates were low. Besides, pts that received adjuvant treatment had increased DFS. The role of adjuvant phase of perioperative treatment is important in pts with higher initial clinical stages and sub-optimal pathological regression.