KEY TAKEAWAYS
- The EGA phase II trial aimed to investigate if adding avelumab to perioperative mDCF chemotherapy increases the pCR rate.
- The primary endpoint was determining the pCR with succession criteria needs to be ≥6 pts showing pCR.
- The study found that giving avelumab and chemotherapy before surgery for gastroesophageal adenocarcinoma was safe and effective and did not seem to depend on known biomarkers.
Chemotherapy before and after surgery can improve cure rates for advanced gastric and esophageal cancers. Immune checkpoint inhibitors are also active in these cancers.
Researchers aimed to test if adding avelumab to perioperative modified docetaxel/cisplatin/5-FU(mDCF) chemotherapy increases the pathologic complete response(pCR) rate, a potential surrogate for overall survival(OS), compared to a historical pCR rate of 7%.
The study’s primary endpoint was pCR in ≥6 patients (pts). Inclusion criteria were histologically proven GEA, locally advanced disease (cT3-4 and/or N+), adequate organ function, and WHO performance status 0-1, while exclusion criteria were other histology, metastatic stage, immunosuppressants, serious autoimmune disease, >10 mg prednisone/d. Adverse events(AEs) were recorded per NCI CTCAE. Pathological response and TRG per CAP criteria were 0=complete, 1=near complete, 2=moderate, and 3=poor/no response. Data presented as median (range) and survival was determined by KM.
The study enrolled 51 pts(45 M/6 F), aged 64 (18-79), ECOG 0 (35) and 1 (16), 1 patient withdrew consent after 2 treatment cycles and was excluded from the efficacy analysis. Tumor anatomic sites were present at esophagus = 19 (38%), gastroesophageal junction = 21 (42%), and subcardia stomach = 10 (20%). Staging was found to be cT3 (88%), cT4 (6%), N+ (62%). All adenocarcinoma; dMMR in 9/50 (18%); CPS<1, 1-5, 6-10, >10 in 0%/33%/27%/40%. Pre-operative cycles were administered to 48/50 (96%), ≥2 adjuvant cycles in 36/50, and all 8 cycles in 23/50 (46%). Grade 3-4 toxicity was identified in the GI tract (diarrhea 4%), respiratory system (pneumonia 4%), and endocrine system (adrenal insufficiency 2%). Common side effects (grades 1-2, incidence >15%) were fatigue, diarrhea, and skin rash/pruritus. Post-operative mortality at 30 and 90 days were 0/50 (0%) and 1/50 (2%).R0 resection was achieved in 48/50 (96%), and a median of 36 (13-78) lymph node resected. The pathological response was TRG 0/1/2/3 on 7/2/16/25 with pCR in 7 (14%), meeting the primary endpoint. Major pathologic response (TRG 0 and 1) in 9 (18%), without CPS or dMMR correlation. At 37.5 (9-71) months follow-up, OS at 1, 2, and 3 years is 93.6%, 75.7%, and 69.2%. MPR shows a trend of improved survival (P= 0.06).
The study found that giving avelumab and chemotherapy (mDCF) before surgery for gastroesophageal adenocarcinoma is safe and effective and does not seem to depend on known biomarkers.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.4055#
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03288350
Thierry Alcindor, Pierre-Olivier Fiset, Touhid Opu, Mehrnoush Dehghani, Nicholas Bertos, Carmen L. Mueller, Jonathan Cools-Lartigue, Marc Hickeson, Victoria Marcus, Sophie Camilleri-Broët, Alan Spatz, Gertruda Evaristo, Mina Farag, Giovanni Artho, Arielle Elkrief, Ramy Saleh, Veena Sangwan, and Lorenzo Ferri. DOI: 10.1200/JCO.2023.41.16_suppl.4055 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 4055-4055.
