1581P - Total neoadjuvant chemotherapy with FOLFIRINOX regimen in patients with resectable locally advanced gastric and gastroesophageal junction cancer

Background

Surgery with perioperative chemotherapy has been standard of care in patients with locally advanced gastric and gastroesophageal junction (GEJ) cancer since FLOT4-AIO trial. However, less than half of patients complete all adjuvant cycles. We studied total neoadjuvant chemotherapy with FOLFIRINOX regimen followed by surgery in this setting.

Methods

We conducted non-randomized, open-label, single-center phase II study in 119 patients with locally advanced resectable gastric and GEJ cancer. Sixty patients were enrolled to received 8 cycles of FOLFIRINOX preoperatively. This prospective cohort was compared to the retrospective cohort (n = 59), that received standard perioperative FLOT regimen (4 cycles before and 4 cycles after surgery). The primary endpoint was disease-free survival (DFS). Secondary endpoints were safety profile and pathological complete response rate (pCR).

Results

In the FOLFIRINOX and FLOT groups 78,6% and 77,8% of patients completed all planned cycles and underwent surgery, respectively. Dose reductions and drug withdrawal rates were higher in the FLOT group. More patients achieved pCR and near-pCR in the FLOT group by three different tumor regression grading systems (TRG 1a/b by Becker, 1/2 by Mandart, and 3/4 by Lavnikova): 47,7%, 40,5%, and 35,7% in the FLOT group and 25%, 27,3%, and 29,6% in the FOLFIRINOX group, respectively, though statistically insignificant. pCR or partial pathological response by any of TRG systems did not predict one-year DFS regardless of the treatment regimen. One-year DFS was numerically higher in the FOLFIRINOX group - 90,4% vs 67,5 % in the FLOT group (hazard ratio [HR] 0,65, 95% CI 0,29 – 1,45, p=0,29). The risk of recurrence in the FOLFIRINOX group was lower than in the FLOT group (odds ratio [OR] 0,40, 95% CI 0,16-0,97, p=0,047). Regional lymph node involvement (ypN2), lymphatic, vascular and perineural invasion negatively affected DFS (p=0,046; p=0,014; p=0,0021; p=0,04, respectively).

Conclusions

The total neoadjuvant chemotherapy with FOLFIRINOX regimen in patients with locally advanced gastric and GEJ cancer demonstrated comparable to the perioperative FLOT one-year DFS rate regardless of pCR and manageable safety profile.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.