Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_CFF0D10D1EFA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial.
Journal
Nature medicine
Author(s)
Verschoor Y.L., van de Haar J., van den Berg J.G., van Sandick J.W., Kodach L.L., van Dieren J.M., Balduzzi S., Grootscholten C., IJsselsteijn M.E., Veenhof AAFA, Hartemink K.J., Vollebergh M.A., Jurdi A., Sharma S., Spickard E., Owers E.C., Bartels-Rutten A., den Hartog P., de Miranda NFCC, van Leerdam M.E., Haanen JBAG, Schumacher T.N., Voest E.E., Chalabi M.
ISSN
1546-170X (Electronic)
ISSN-L
1078-8956
Publication state
Published
Issued date
02/2024
Peer-reviewed
Oui
Volume
30
Number
2
Pages
519-530
Language
english
Notes
Publication types: Clinical Trial, Phase II ; Journal Article
Publication Status: ppublish
Abstract
Gastric and gastroesophageal junction (G/GEJ) cancers carry a poor prognosis, and despite recent advancements, most patients die of their disease. Although immune checkpoint blockade became part of the standard-of-care for patients with metastatic G/GEJ cancers, its efficacy and impact on the tumor microenvironment (TME) in early disease remain largely unknown. We hypothesized higher efficacy of neoadjuvant immunotherapy plus chemotherapy in patients with nonmetastatic G/GEJ cancer. In the phase 2 PANDA trial, patients with previously untreated resectable G/GEJ tumors (n = 21) received neoadjuvant treatment with one cycle of atezolizumab monotherapy followed by four cycles of atezolizumab plus docetaxel, oxaliplatin and capecitabine. Treatment was well tolerated. There were grade 3 immune-related adverse events in two of 20 patients (10%) but no grade 4 or 5 immune-related adverse events, and all patients underwent resection without treatment-related delays, meeting the primary endpoint of safety and feasibility. Tissue was obtained at multiple time points, allowing analysis of the effects of single-agent anti-programmed cell death ligand 1 (PD-L1) and the subsequent combination with chemotherapy on the TME. Twenty of 21 patients underwent surgery and were evaluable for secondary pathologic response and survival endpoints, and 19 were evaluable for exploratory translational analyses. A major pathologic response (≤10% residual viable tumor) was observed in 14 of 20 (70%, 95% confidence interval 46-88%) patients, including 9 (45%, 95% confidence interval 23-68%) pathologic complete responses. At a median follow-up of 47 months, 13 of 14 responders were alive and disease-free, and five of six nonresponders had died as a result of recurrence. Notably, baseline anti-programmed cell death protein 1 (PD-1) <sup>+</sup> CD8 <sup>+</sup> T cell infiltration was significantly higher in responders versus nonresponders, and comparison of TME alterations following anti-PD-L1 monotherapy versus the subsequent combination with chemotherapy showed an increased immune activation on single-agent PD-1/L1 axis blockade. On the basis of these data, monotherapy anti-PD-L1 before its combination with chemotherapy warrants further exploration and validation in a larger cohort of patients with nonmetastatic G/GEJ cancer. ClinicalTrials.gov registration: NCT03448835 .
Keywords
Humans, Neoadjuvant Therapy, Programmed Cell Death 1 Receptor, Adenocarcinoma/drug therapy, Adenocarcinoma/pathology, Stomach Neoplasms/drug therapy, Stomach Neoplasms/pathology, Esophagogastric Junction/pathology, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Tumor Microenvironment, Esophageal Neoplasms, Antibodies, Monoclonal, Humanized
Pubmed
Web of science
Open Access
Yes
Create date
12/01/2024 12:32
Last modification date
27/02/2024 8:30
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