title: Combining Poly-(ARD-Ribose) Polymerase and Programmed Cell Death Protein 1 Inhibition in a Patient with Esophagogastric Adenocarcinoma
creator: Artzenroth, Jule Cecilia
creator: Tintelnot, Joseph
creator: Haag, Georg Martin
creator: Gökkurt, Eray
creator: Steffens, Johann
creator: Stein, Alexander
subject: ddc-610
subject: 610 Medical sciences Medicine
description: Introduction: Esophagogastric adenocarcinoma (EGA) is one of the leading causes of cancer-related mortality worldwide. Therapeutic options are limited for patients with recurrent or metastatic disease. Targeted therapy may be a suitable treatment for selected patients, but its efficacy remains elusive. Case Presentation: Here, a 52-year-old male patient with advanced EGA Siewert Type II shows a significant response to combination therapy with olaparib and pembrolizumab. After progression following first- and second-line therapy, including a programmed cell death ligand 1 (PD-L1) inhibitor, next-generation sequencing of a tumor sample was performed to identify possible molecular targets. A mutation in RAD51C, a member of the homology-directed repair (HDR) system, was identified in addition to high PD-L1 expression. As a result, therapy with the poly-(ARD-Ribose) polymerase (PARP) inhibitor olaparib and the programmed cell death protein 1 (PD1)-inhibitor pembrolizumab was initiated. A durable partial response lasting for more than 17 months was observed. A second molecular profiling from a newly occurring subcutaneous metastasis showed a loss of FGF10 but no fluctuations in the gene alteration of RAD51C and SMARCA4. Interestingly, the new lesion showed HER2-positivity (immunohistochemistry 3+ and fluorescence in situ hybridization [FISH]-positivity) in 30% of tumor cells. Conclusion: In this case, a long-lasting response to the combination of olaparib and pembrolizumab was observed despite previous treatment with a PD-L1 inhibitor. This case illustrates the need for further clinical trials to analyze the efficacy of PARP inhibitor combinations in EGA.
publisher: S. Karger AG, Medical and Scientific Publishers
date: 2023
type: Article
type: info:eu-repo/semantics/article
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/35301/1/ORT530801.pdf
identifier: DOI:10.11588/heidok.00035301
identifier: https://doi.org/10.1159/000530801
identifier: urn:nbn:de:bsz:16-heidok-353017
identifier:   Artzenroth, Jule Cecilia ; Tintelnot, Joseph ; Haag, Georg Martin ; Gökkurt, Eray ; Steffens, Johann ; Stein, Alexander  (2023) Combining Poly-(ARD-Ribose) Polymerase and Programmed Cell Death Protein 1 Inhibition in a Patient with Esophagogastric Adenocarcinoma.  Oncology Research and Treatment, 46 (7-8).  pp. 320-325.  ISSN 2296-5270 (Druck-Ausg.); 2296-5262 (Online-Ausg.)     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/35301/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng