Abstract 2753
Background
Perioperative chemotherapy improves survival in locally advanced gastric and esophago-gastric adenocarcinoma (EGA), in comparison with surgery alone. The pathologic complete response rate (pCR) is as a possible surrogate for survival and is influenced by the chemotherapy regimen given. We and others have previously described the efficacy of docetaxel/cisplatin/fluorouracil (DCF) in the perioperative management of this cancer. Research by other groups has shown equivalent efficacy and lesser toxicity of a modified DCF regimen. Given the promising activity of immune checkpoint inhibitors in these malignancies, we hypothesize that the addition of immunotherapy with avelumab, an anti-PD-L1 agent, to mDCF chemotherapy (immunochemotherapy), will result in improved outcomes. Our trial is approved by Health Canada and our hospital Research Ethics Board. It is registered as NCT03288350 (www.clinicaltrials.gov).
Trial design
Eligible patients will receive neoadjuvant therapy consisting of 4 cycles of avelumab + mDCF, followed by surgery and assessment of pathologic response. Then they will receive 4 cycles of adjuvant therapy of mDCF + avelumab. Primary endpoint is pCR. Secondary endpoints are 2-year disease-free survival rate and incidence of non-hematological grade 3-4. Exploratory translational studies are planned. We hypothesize that immunochemotherapy will yield a pCR rate of 20% in comparison with 7% for chemotherapy only (historical data). Main inclusion criteria are : diagnosis of gastric or EGA adenocarcinoma, locally advanced disease, adequate organ function, performance status 0-1, stages Ib-III. Main exclusion criteria are: other histologies, metastatic disease, use of immunosuppressants, serious autoimmune disease, daily prednisone intake > 10 mg or equivalent. To validate the hypothesis with power of 0.80 and α error of 0.05, 50 participants will be needed. Enrolment has started and is following a 2-stage Simon rule : accrual will stop if no more than 1 pCR is seen in the first 16 patients ; if more than 6/50 patients show pCR, the trial will be considered successful in that the alternate hypothesis cannot be rejected.
Clinical trial identification
NCT03288350, posted September 20, 2017.
Legal entity responsible for the study
Research Institute of the McGill University Health Centre.
Funding
EMD Serono.
Editorial Acknowledgement
Disclosure
T. Alcindor: Consultant: EMD Serono, BMS, Lilly. J. Asselah: Taiho, Ipsen, Pfizer. M. Vanhuyse: BMS. All other authors have declared no conflicts of interest.