Abstract 1429P
Background
Perioperative chemotherapy improves cure rate in locally advanced gastroesophageal adenocarcinoma (GEA), and immune checkpoint inhibitors are active at the metastatic stage. This trial tests the hypothesis that the addition of Avelumab to perioperative chemotherapy will increase the pathologic complete response rate (pCR) in comparison with historical controls.
Methods
Phase II study of Avelumab + chemotherapy (mDCF) given every 2 weeks for 4 cycles before and after surgery. Main inclusion criteria: GEA, cT3 and/or cN+, WHO PS 0-1. Main exclusion criteria: other histology, metastatic stage, use of immunosuppressants, serious autoimmune disease, daily intake >10 mg prednisone. Staging studies: CT, PET-CT, endoscopic ultrasound, diagnostic laparoscopy. Surgical resection: D2 lymphadenectomy, en-bloc esophagectomy for type I/II GEJ tumors. Statistical hypothesis: pCR is defined as tumor regression (modified Ryan scheme) grades 0-1; this experimental regimen will result in a 20% rate of pCR, compared with 7% with chemotherapy alone. Simon 2-stage design: if less than 2 pCR are seen in the first 16 patients, the study will be closed. The null hypothesis cannot be rejected if at least 6 pCR are seen in the first 50 patients. All adverse effects are prospectively recorded per CTCAE guidelines in patients who have received at least one treatment cycle.
Results
Feb 2018-Feb 2020: 28 patients enrolled (25 M/3 F, age 45-78). Location: gastroesophageal junction (23), stomach (5). Staging: cT3 (25), cT4 (1), cN+ (20). Grade 3 toxicity: stomatitis (2/28); nausea (2/28); vomiting (1/28); diarrhea (1/28); hypothyroidism (1/28); arthralgia (3/28); neutropenia (1/28). Grade 4 toxicity: pneumonia (1/28); neutropenia (2/28). Postoperative 30-day mortality: 0%. One patient was excluded from efficacy analyses for M1 staging; 27 patients underwent surgery, 26 with R0 (96%). Six cases (22%) show pCR: 3 grade 0 (11%) and 3 grade 1 (11%) tumor regressions.
Conclusions
The combination of mDCF chemotherapy with Avelumab demonstrates a promising safety and activity profile. Ongoing laboratory investigations are underway to correlate our findings with tumor molecular features before exposure to treatment.
Clinical trial identification
NCT03288350.
Editorial acknowledgement
Legal entity responsible for the study
Research Institute of the McGill University Health Centre (RI-MUHC).
Funding
EMD Serono.
Disclosure
T. Alcindor: Advisory/Consultancy: Roche; Research grant/Funding (self): EMD Serono; Advisory/Consultancy: Eisai; Advisory/Consultancy: Taiho; Advisory/Consultancy: Merck; Advisory/Consultancy: Pfizer. All other authors have declared no conflicts of interest.