1430P - Frequency of PD-L1 positivity and microsatellite instability (MSI) in the DANTE trial: Perioperative atezolizumab with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma. A randomized, open-label phase IIb trial of the German gastric group at the AIO and SAKK

Background

The DANTE study evaluates atezolizumab in the perioperative treatment of locally advanced, potentially resectable gastric or GEJ adenocarcinoma in combination with FLOT. Here, we report preliminary data for the clinical baseline, along with PD-L1 expression and MSI.

Methods

DANTE is a bi-national, prospective, multicenter, investigator-initiated, phase IIb trial. Patients (pts) with esophagogastric adenocarcinoma (GEJ ≥cT2 and/or N+) without distant metastases are enrolled. Pts are randomized 1:1 to receive 4 cycles perioperative FLOT q2w (arm B) or 4 cycles perioperative FLOT + atezolizumab at 840 mg q2w and subsequent atezolizumab monotherapy for 8 cycles at 1200 mg q3w (arm A). Primary endpoint is time to disease progression or relapse after surgery (PFS/DFS). PD-L1 and MSI status were centrally evaluated. The analysis of PD-L1 is based on 163 evaluable pts.

Results

By Oct 2020, the trial has been fully recruited with 295 pts (74% male). The median age was 61y. Laurén classification was 42% intestinal, 22% diffuse, 10% mixed and 26% not evaluable. 61% of pts had an adenocarcinoma of the GEJ. Overall, 22 (7%) pts were assessed MSI. Among baseline criteria, MSI frequency was highest in pts aged ≥70 (16%) and lowest in the diffuse type (3%). 10/22 MSI pts had a PD-L1 CPS ≥1 and 6 had CPS ≥5. CPS ≥10 was more frequent in the GEJ vs. the GC subgroup (25% vs. 13%).

Conclusions

7% of pts were MSI and 63% were PD-L1+ (CPS ≥1). MSI appeared to increase with age and to be more frequent in GC tumors and in the intestinal/mixed subtype. PD-L1 was more frequently expressed in the GEJ subgroup. Approximately half of the MSI cases were PD-L1 positive. Table: 1430P

Overview of PD-L1 expression and MSI status according to tumor location

Clinical trial identification

EudraCT: 2017-001979-23. NCT03421288.

Editorial acknowledgement

Legal entity responsible for the study

Institut für Klinische Krebsforschung IKF GmbH.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

P.C. Thuss-Patience: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Servier. A. Kretzschmar: Financial Interests, Advisory Role: Teva; Financial Interests, Advisory Role: Roche; Financial Interests, Advisory Role: Shire; Financial Interests, Advisory Role: Amgen; Financial Interests, Other, Travel: PharmaMar; Financial Interests, Other, Travel: Merck; Financial Interests, Other, Travel: Ipsen; Financial Interests, Other, Travel: Medac; Financial Interests, Invited Speaker: Roche; Financial Interests, Invited Speaker: Merck; Financial Interests, Invited Speaker: Shire; Financial Interests, Invited Speaker: Amgen; Financial Interests, Invited Speaker: Novatis; Financial Interests, Invited Speaker: Medac; Financial Interests, Invited Speaker: Esai; Financial Interests, Invited Speaker: Servier; Financial Interests, Invited Speaker: Sanofi. E. Goekkurt: Financial Interests, Advisory Board: BMS; Financial Interests, Advisory Board: MSD; Financial Interests, Advisory Board: Roche; Financial Interests, Advisory Board: Sanofi; Financial Interests, Advisory Board: Merck. G.M. Haag: Financial Interests, Advisory Role: BMS; Financial Interests, Other, Travel: BMS; Financial Interests, Advisory Role: MSD S&D; Financial Interests, Invited Speaker: MSD S&D; Financial Interests, Advisory Role: Lilly; Financial Interests, Invited Speaker: Lilly; Financial Interests, Invited Speaker: Servier; Financial Interests, Research Grant: Nordic Pharma; Financial Interests, Research Grant: Taiho Pharmaceutical; Financial Interests, Advisory Role: EsoCap; Financial Interests, Research Grant: MSD S&D; Financial Interests, Other, Travel: Lilly. T.O. Götze: Financial Interests, Personal, Advisory Board: Bayer,; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board: MSD Oncology; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Invited Speaker: Servier; Non-Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Personal and Institutional, Research Grant: DFG; Non-Financial Interests, Personal and Institutional, Research Grant: Deutsche Krebshilfe; Non-Financial Interests, Personal and Institutional, Research Grant: Gemeinsamer Bundesausschuss; Non-Financial Interests, Personal and Institutional, Research Grant: Lilly. S. Al-Batran: Financial Interests, Advisory Role: Roche; Financial Interests, Advisory Role: Celgene; Financial Interests, Advisory Role: Lilly; Financial Interests, Advisory Role: BMS; Financial Interests, Advisory Role: Merck; Financial Interests, Advisory Role: Nordic Bioscience; Financial Interests, Advisory Role: Merck S&D; Financial Interests, Speaker’s Bureau: Lilly; Financial Interests, Speaker’s Bureau: Celgene; Financial Interests, Speaker’s Bureau: AIO gGmbH; Financial Interests, Speaker’s Bureau: Forum für Medizinische Fortbildung; Financial Interests, Speaker’s Bureau: MCI group; Financial Interests, Speaker’s Bureau: Nordic Bioscience; Financial Interests, Ownership Interest: Institut für Klinische Krebsforschung IKF GmbH; Financial Interests, Research Grant: Celgene; Financial Interests, Research Grant: Lilly; Financial Interests, Research Grant: Medac; Financial Interests, Research Grant: Hospira; Financial Interests, Research Grant: Sanofi; Financial Interests, Research Grant: German Cancer Aid; Financial Interests, Research Grant: German Research Foundation; Financial Interests, Research Grant: Federal Ministry of Education and Research; Financial Interests, Research Grant: Merck; Financial Interests, Research Grant: Roche; Financial Interests, Research Grant: Vifor Pharma. All other authors have declared no conflicts of interest.