Long-term survival results of perioperative chemoimmunotherapy with DCF and avelumab in locally advanced gastro-esophageal adenocarcinoma.

Abstract

4096 Background: We have shown that avelumab, an anti-PD-L1 antibody, added to perioperative modified DCF chemotherapy (aDCF regimen), improves the pathologic complete response rate from 7% to 14% in locally advanced gastro-esophageal adenocarcinoma (GEA), in comparison to historical controls from our own institution. Little is known about the long-term survival results obtained with perioperative chemoimmunotherapy, a new standard of care. We are here reporting the 5-year survival results of our cohort of patients treated with aDCF. Methods: Single-arm phase II study of aDCF given every 2 weeks for 4 cycles before and after surgery with planned sample size of 50 operated patients in order to test hypothesis that pCR rate would improve from 7 to 20%. Main inclusion criteria were: histologically proven GEA, locally advanced disease (cT3-4 and/or N+), adequate organ function, WHO performance status 0-1. Main exclusion criteria were: histology other than adenocarcinoma, metastatic disease (M1), use of immunosuppressants, serious autoimmune disease, daily intake of more than 10 mg of prednisone. Pathological response (Tumour Regression Grade -TRG) was determined by the College of American Pathologists criteria: 0 = complete;1 = near complete/microscopic residual disease; 2 = moderate; 3 = poor/no response. MPR was defined as TRG 0 or 1. Data presented as median (range), KM determined survival. Patients with less than 5 years follow-up and who were disease free / alive were censored. Results: One of the 51 patients enrolled into the trial withdrew consent, leaving 50 patients in the survival analysis. Clinical disease burden was high (cT3 44/50, 88%, N+ 31/50, 62%) with 49/50 (98%) completing neoadjuvant aDCF. All patients proceeded to surgery with MPR found in 9/50 (18%) patients. The median follow-up for the cohort was 71.5 months (range 43-105) with an estimated mean DFS and OS of 62.5 months and 68.5 months corresponding to a 5-year DFS and OS of 55.3% and 61.1%. For patients with MPR, 5-year DFS and OS were 100%. There were no new safety signals. Conclusions: Perioperative aDCF resulted in long-term survival in the majority of patients treated on our trial, bringing more evidence that chemoimmunotherapy improves outcomes of patients with locally advanced GEA. Those outcomes seem enhanced among patients with MPR. Clinical trial information: NCT03288350 .