Safety and efficacy of intensified preoperative management of locally advanced gastrorsophageal junction cancer (INPROVE).

Abstract

e16110 Background: The optimal management of locally advanced gastroesophageal junction adenocarcinoma (LAGEJad) is not fully established yet. Both neoadjuvant chemoradiotherapy (CRT) and perioperative taxane-based triplet chemotherapy (CT) are acknowledged treatment options for Siewert I and II cancers. In this retrospective study, we aimed to assess the safety and outcomes of an intensified preoperative regimen combining taxane-based triplet CT and CRT. Methods: We conducted a retrospective analysis of a cohort comprising 16 consecutive HER2 negative patients (pts) with LAGEJad treated at the Centro di Riferimento Oncologico of Aviano between 2019 and 2022. All pts received induction CT (iCT) consisting of fluoropyrimidine, oxaliplatin and docetaxel, followed by CRT (45Gy/25Fr) with simultaneous boost and concomitant CT. Surgery (Ivor-Lewis or McKeown) was performed 8 weeks post-CRT. Clinico-pathological (CP) and treatment features were analyzed using logistic regression to assess their association with response to iCT-CRT. The association of iCT-CRT with survival outcomes was investigated using the Kaplan-Meier method. Results: Key CP data are summarized in Table 1. Median age was 59 years, all pts were male. At diagnosis, 81.2% of pts exhibited cT3+ and cN+ disease. All pts received iCT and CRT. The rate of partial responses was 50% after iCT and 68.8% after CRT. Overall, 12 pts underwent surgery, all achieving R0 resections within a median timeframe of 9 [8.5;11] weeks post-CRT. Among them, 25% had a pathologic complete response, while 62.5% attained a Mandard tumor regression grade (TRG) of 1-2. No new safety signals emerged from iCT (only 2 pts had ≥G3 diarrhea) or CRT (≥G3 mucositis occurred in 6.2% and anemia in 6.2% of pts). No significant surgical delays were observed, although 5 pts experienced post-operative complications (4 grade I, 1 grade IIa). There were no statistically significant associations between CP variables and response to the iCT-CRT. Relapses were seen in 8 pts (2 locoregionally); 3-year survival was 46%. Median event-free survival was 5 [5;11] months, while median overall survival 34 [14;NR] months. Conclusions: The intensification of preoperative treatment in pts with LAGEJad is active and safe: the surgical schedule was not significantly delayed, and the safety profile remained comparable to standard regimens, with no major complications reported. Randomized clinical trials are ongoing to assess the clinical benefits of this approach. [Table: see text]