Multicenter, randomized phase II study of neoadjuvant pembrolizumab plus chemotherapy and chemoradiotherapy in esophageal adenocarcinoma (EAC).

• DOI: 10.1200/jco.2021.39.15_suppl.4005
• Publication Date: 2021-06-02T14:06:35Z
• Authors: Manish A. Shah; Khaldoun Almhanna; Syma Iqbal; Prashant Thakkar; Bryan J. Schneider; Rhonda Yantiss; Yiru Wu; Emma Futamura; Jeffrey L. Port; Cathy Spinelli; Sandipto Sarkar; Paul J. Christos; Gagandeep Brar; Doron Betel; Nicholas J. Sanfi...; Nasser K. Altorki
• Keywords: Carboplatin; Chemoradiotherapy; Pemetrexed; Clinical endpoint; Neoadjuvant Therapy

4005 Background: Recent transformative studies in the treatment of EAC support adjuvant nivolumab for patients with residual disease following neoadjuvant chemoradiotherapy (CRT) (Checkmate 577) and pembrolizumab (P) chemotherapy untreated metastatic (Keynote 590). We hypothesized that pre-operative P combined CRT can further improve outcomes locally advanced EAC. Methods: Patients cT3-4Nx or T2N1 M0 gastroesophageal junction (GEJ) adenocarcinoma eligible curative surgery were randomized (1:1) to receive either full-dose paclitaxel (T)/ carboplatin (C) T/C + induction therapy. All then received weekly T/C, RT 41.4Gy 23 fractions, every 3 weeks. Following resection, one year. The primary endpoint is rate major pathologic response (MPR), defined as complete near ( < 10% cancer), 80% power 0.1 one-sided significance level detect difference between a MPR proportion 30% (historical control) an alternative hypothesis 47% (with preoperative P). Tissue was collected tumor immune microenvironment (TIME) analysis including bulk single cell RNA(scRNA) expression analysis, DNA sequencing, flow cytometry. Results: From 8/4/17 10/26/20, 40 enrolled: median age 68 [38-81], male 32, esophagus/GEJ type I (n = 16), GEJ II/III 24). well tolerated, no grade 3-4 adverse events attributed P. Notable toxicity included pneumonitis (13%), anastomotic leak infection (35%). In 31 evaluable date, 50.0% (95% CI, 32.7%-67.3%). 1-yr free survival 100% vs. 31.8% without MPR, p 0.002. Esophageal/GEJ cancers had significantly higher when compared (76.9% vs 37.5%, 0.03). scRNA seq on > 100,000 cells revealed EAC/GEJ infiltration activated dendritic (p 0.12), whereas tumors have B 0.02). Conclusions: addition safe associated historical data. found be enriched II/III, important differences baseline microenvironment. Clinical trial information: NCT02998268.