Combining Poly-(ARD-Ribose) Polymerase and Programmed Cell Death Protein 1 Inhibition in a Patient with Esophagogastric Adenocarcinoma

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 -