Combining Poly-(ARD-Ribose) Polymerase and Programmed Cell Death Protein 1 Inhibition in a Patient with Esophagogastric Adenocarcinoma
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Combining Poly-(ARD-Ribose) Polymerase and Programmed Cell Death Protein 1 Inhibition in a Patient with Esophagogastric Adenocarcinoma. / Artzenroth, Jule Cecilia; Tintelnot, Joseph; Haag, Georg Martin; Gökkurt, Eray; Steffens, Johann; Stein, Alexander.
In: ONCOL RES TREAT, Vol. 46, No. 7-8, 2023, p. 320-325.Research output: SCORING: Contribution to journal › Case report › Research › peer-review
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TY - JOUR
T1 - Combining Poly-(ARD-Ribose) Polymerase and Programmed Cell Death Protein 1 Inhibition in a Patient with Esophagogastric Adenocarcinoma
AU - Artzenroth, Jule Cecilia
AU - Tintelnot, Joseph
AU - Haag, Georg Martin
AU - Gökkurt, Eray
AU - Steffens, Johann
AU - Stein, Alexander
N1 - Case Report
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Male
KW - Humans
KW - Ribose
KW - B7-H1 Antigen/metabolism
KW - Programmed Cell Death 1 Receptor
KW - In Situ Hybridization, Fluorescence
KW - Adenocarcinoma/pathology
KW - DNA Helicases
KW - Nuclear Proteins/genetics
KW - Transcription Factors/genetics
U2 - 10.1159/000530801
DO - 10.1159/000530801
M3 - Case report
C2 - 37231946
VL - 46
SP - 320
EP - 325
JO - ONCOL RES TREAT
JF - ONCOL RES TREAT
SN - 2296-5270
IS - 7-8
ER -