Clinical and metabolic predictors of complete response after neoadjuvant immune checkpoint blockade in resectable gastroesophageal adenocarcinoma (GEC).

Abstract

e16149 Background: Perioperative durvalumab + FLOT improves overall survival and is a new treatment option for patients with resectable GEC. FDG-PET SUV decline of ≥35% is commonly used as a benchmark of treatment response. We correlated FDG-PET and endoscopic response with pathologic outcomes to evaluate their utility in selecting patients for non-operative management (NOM). Methods: Patients with localized MSS GEC treated with curative intent ICB+chemotherapy at MSK between 2020-2025 were retrospectively analyzed. Association of primary tumor baseline FDG avidity and %SUV change with surgical pathological outcomes [pathologic complete response (pCR), defined as absence of residual carcinoma; ypT3-4; and ypN+] was determined. High avidity was defined as SUV > 8, metabolic response as 35% reduction in FDG, and clinical complete response (cCR) as a negative biopsy on post-neoadjuvant therapy endoscopy (EGD). Results: Among 48 patients (20 gastric, 28 GEJ) who received neoadjuvant FLOT (n = 30) or FOLFOX (n = 18) + ICB, 43 underwent surgery. pCR occurred in 7/43 [16.3%; pCR with FOLFOX+ICB 1/13 (7.7%); 6/30 (20%) with FLOT+ ICB]. 35/48 underwent FDG PET at baseline and after therapy and had FDG-avid disease at baseline (SUV > 5). Median baseline SUV was 8.7 (range 5.1-37.5) with median %SUV change -55% (range +12% to -100%) after therapy. Baseline SUV (≥8 vs < 8), %SUV reduction (≥35% vs < 35 and ≥75% vs < 35%), and residual post-therapy avidity were not associated with pCR, ypT3–4 disease, or ypN+ disease. Findings were consistent by site (gastric vs GEJ/esophagus) and among patients receiving triplet chemotherapy. Compared to patients without cCR or pCR (n = 26 PET evaluable), patients with cCR or pCR (n = 9 PET evaluable) had significantly reduced median post-treatment avidity (SUV 2.8 vs 4.1; p = 0.03), however the groups did not significantly differ in median percent reduction in avidity or percent with post-treatment SUV < 3. Among 6 patients with complete resolution of PET avidity, 2/6 had pCR, 1/6 had cCR and proceeded to NOM, and 3/6 had residual disease including 2 with ypT4aN+ disease. 12/48 patients had an EGD after neoadjuvant therapy; 5 had cCR of whom 3 had residual FDG avidity on post-treatment PET. 1/5 of the cCR had pCR; the other 4 proceeded to NOM. In both cases of complete metabolic resolution and cCR, patients proceeded to NOM with no evidence of recurrence after minimum follow up of 3 years. Conclusions: Percent reduction in primary tumor PET avidity following neoadjuvant chemoimmunotherapy in resectable GEC was not associated with surgical pathology outcomes in our cohort. The combination of PET and endoscopy may better select patients for NOM paradigms, though higher resolution tools to assess for residual disease are needed. Multimodal predictive models for surgical pathology and long-term survival outcomes are being developed.