A phase II feasibility trial of neoadjuvant chemoradiotherapy combined with atezolizumab for resectable esophageal adenocarcinoma: The PERFECT trial.

Abstract

4045 Background: The CROSS study demonstrated the superiority of neoadjuvant chemoradiotherapy (nCRT) over surgery alone (van Hagen et al. NEJM. 2012). However, for resectable esophageal adenocarcinoma (rEAC) 5y survival is only 43%. PD1/PDL1 checkpoint inhibitors have shown promising efficacy for several cancer types, including esophageal cancer. To further improve outcomes in rEAC, we performed a phase II trial of nCRT combined with atezolizumab, a PD-L1 inhibitor. Methods: Pts with rEAC received standard dose CROSS regimen (5 cycles of IV: carboplatin AUC2, paclitaxel 50 mg/m2 and concurrent 23 fractions of 1.8 Gy on weekdays) with atezolizumab (5 cycles: 1200 mg IV, 3 weekly). Primary endpoint was the percentage of pts completing treatment with atezolizumab. Secondary endpoints included: toxicity, post-operative complications (Clavien-Dindo), Mandard score, R0 resection rate, PFS and OS. In total 40 pts will be enrolled. Results: Since July 2017, 39 pts have been enrolled (87% males, median age 63). Neoadjuvant treatment was completed by 31 pts and is ongoing in 8 pts. All cycles/fractions of nCRT were administered in 29/31 pts; 26 pts completed all cycles of atezolizumab, 24 pts finished complete neoadjuvant treatment. Reasons for missing any cycle of chemotherapy/atezolizumab included: toxicity (6 pts, in 3/6 pts immune-related adverse events (irAE)) and progression (1 pt). Grade 3-4 toxicity was observed in 15/31 pts (6/31 irAEs of any grade) which did not delay surgery. Thus far 23/31 pts were resected, 3 pts are planned for surgery, 3 pts had interval metastases preoperatively, 1 pt died during treatment (pulmonary embolism), and 1 pt declined surgery. Clavien-Dindo grade 3-4 complications were seen in 11/23 pts with no surgery related mortality. A pathological complete response (pCR), Mandard 1 was seen in 9/23 (39%) pts. All patients underwent an R0 resection. Updated results will be presented at the meeting. Conclusions: Based on data thus far, atezolizumab added to nCRT is feasible. A pCR was observed in 39% of patients, which is promising compared to 23% in the CROSS study. Treatment is associated with irAE which are manageable. Biomarker research will be performed on blood (circulating tumor DNA), tissue (immune microenvironment) and feces (microbiome). Clinical trial information: NCT03087864.