Abstract 5217
Background
Overall survival (OS) of locally advanced esophageal cancer remains poor with a 5-year survival of 15-34%. The standard treatment is definitive radiotherapy delivered with oxaliplatin-based chemotherapy (RCT). Majority of patients (pts) die due to non-complete response, local recurrence and/or metastatic progression and the efficacy of definitive RCT need to be increased. The immune checkpoint inhibitors, anti-programmed death 1 (PD-1) and anti-programmed death ligand 1 (PD-L1), demonstrated promising antitumor activity and manageable safety profile when used as monotherapy in metastatic esophageal squamous cell carcinoma. PD-L1 expression increased in esophageal cancer pts after neoadjuvant RCT but still associated with poor OS. The immune tumor microenvironment for tumor response has raised novel hypotheses regarding newer immunomodulatory approaches during radiotherapy, especially abscopal effect to improve local and distant outcome. Durvalumab (MEDI4736) is a selective high affinity human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80. We hypothesize that combining durvalumab with RCT can increase local response to treatment and prevent distant metastases.
Trial design
This multicentric, open-label, comparative phase II trial plans to randomize (1:1) 120 pts (≥18 years old, WHO <2, unresectable disease) and evaluates the activity of durvalumab (1500 mg) delivered over 12 months in combination with definitive RCT (IMRT 50 Gy for 5 weeks + FOLFOX4 simplified 1 infusion every 2 weeks during 3 months) compared to definitive RCT alone. Given the lack of safety data from this association, a safety run-in of 6 pts is planned. The main objective is to increase 12-months progression-free survival (PFS) centrally reviewed from 50% to 68% (HR = 0.55). 74 events are necessary to detect this difference with a power of 90% using a one–sided logrank test at 10% level of significance. Main secondary endpoints are safety, PFS and quality of life. Ancillary studies mains to identify biomarkers predicting response to treatment. The first patient will be randomized in May 2019 and 12 sites will recruit pts.
Clinical trial identification
NCT03777813.
Editorial acknowledgement
Legal entity responsible for the study
Unicancer GI tumors.
Funding
AstraZeneca.
Disclosure
L. Quero: Research grant / Funding (institution): AstraZeneca. E.L. Cohen-Jonathan Moyal: Research grant / Funding (institution): AstraZeneca. A. Modesto: Research grant / Funding (institution): AstraZeneca. All other authors have declared no conflicts of interest.
Resources from the same session
3248 - Second-line palliative systemic treatment for synchronous metastatic esophagogastric cancer: a population-based study
Presenter: Willemieke Dijksterhuis
Session: Poster Display session 2
Resources:
Abstract
4331 - STING Agonist, ADU-S100, Yields Potent Antitumor Activity and Therapeutically Favorable Immune Profile in an Esophageal Adenocarcinoma Model
Presenter: Ali Zaidi
Session: Poster Display session 2
Resources:
Abstract
1770 - Increased assessment of HER2 in metastatic gastroesophageal cancer patients: a nationwide population-based cohort study
Presenter: Willemieke Dijksterhuis
Session: Poster Display session 2
Resources:
Abstract
3755 - A new docetaxel (DOC)-based triplet regimen does not improve the outcome of metastatic (M) or locally advanced (LA) gastric cancer (GC) as compared with an epirubicin (EPI) standard triplet regimen: a GISCAD trial.
Presenter: Roberto Labianca
Session: Poster Display session 2
Resources:
Abstract
2439 - The analysis of T cell subsets and clinical efficacy of immune checkpoint blockades in patients with advanced gastric cancer using multiplex immunohistochemistry
Presenter: Tae-yong Kim
Session: Poster Display session 2
Resources:
Abstract
2211 - First-line pembrolizumab (P), trastuzumab (T), capecitabine (C) and oxaliplatin (O) in HER2-positive metastatic esophagogastric adenocarcinoma.
Presenter: Yelena Janjigian
Session: Poster Display session 2
Resources:
Abstract
3046 - Monitoring patient-specific mutation in ctDNA and CTC for tumor response evaluation after neoadjuvant chemotherapy in locally advanced gastric cancer (NCT03425058)
Presenter: Tao Fu
Session: Poster Display session 2
Resources:
Abstract
4628 - Gastric cancer screening in BRCA 2 gene mutation carriers: should it be recommended?
Presenter: Inês Oliveira
Session: Poster Display session 2
Resources:
Abstract
2127 - Interim analysis of an observational/translational study for nivolumab treatment in advanced gastric cancer: JACCRO GC-08 (DELIVER trial)
Presenter: Yu Sunakawa
Session: Poster Display session 2
Resources:
Abstract
2264 - Prediction of S-1 adjuvant chemotherapy efficacy in Stage II/III gastric cancer treatment based on comprehensive gene expression analysis
Presenter: Masanori Terashima
Session: Poster Display session 2
Resources:
Abstract