Complete Pathologic Response to PARP Inhibitor Olaparib in a Patient with Stage IVB Recurrent Endometrioid Endometrial Adenocarcinoma

Abstract

Treatment for endometrial cancer is rapidly evolving with the increased use and integration of somatic tumor RNA sequencing in clinical practice. There is a paucity of data regarding PARP inhibition in endometrial cancer given that mutations in homologous recombination genes are rare, and currently no FDA approval exists. A 50-year-old gravida 1 para 1 woman with a diagnosis of stage IVB poorly differentiated endometrioid endometrial adenocarcinoma presented to our comprehensive cancer center. Following surgical staging, she was placed on adjuvant chemotherapy with carboplatin/paclitaxel which was held multiple times due to poor performance status and complications. CT scan of the abdomen and pelvis following cycles 3 of adjuvant chemotherapy showed recurrent progressive disease. She received one cycle of liposomal doxorubicin but discontinued it due to severe cutaneous toxicity. Based on the BRIP1 mutation identified, the patient was placed on compassionate use of Olaparib in January 2020. Imaging during this surveillance period showed a significant decrease in hepatic, peritoneal, and extraperitoneal metastases, and eventually the patient had a clinical complete response in a year. The most recent CT A/P in December 2022 showed no sites of active recurrent or metastatic disease in the abdomen or pelvis. We present a unique case of a patient with recurrent stage IVB poorly differentiated endometrioid endometrial adenocarcinoma with multiple somatic gene mutations including BRIP1, who had a pathologic complete response following compassionate use of Olaparib for 3 years. To our knowledge, this is the first reported case of high grade endometrioid endometrial cancer that has shown a pathologic complete response to a PARP inhibitor.

Keywords: ATM mutation; BRIP1 mutation; Olaparib; PARP inhibition; POLE mutation; RAD51C mutation; TMB high; endometrial cancer; pathologic complete response.

Figure 1

The histologic section of the uterine tumor showed poorly differentiated neoplastic cells with destructive growth pattern, diffusely infiltrating throughout the myometrium. The lower magnification image (4×) showed the presence of lymphovascular space invasion (arrow). The inset shows a high magnification view (40×) of the tumor cells, with high grade cytologic features including nucleomegaly, irregular nuclear contour, stippled to clumped chromatin, and variably prominent nucleoli. Scattered mitotic activity and numerous apoptotic cells can be seen, signifying high proliferative activity.

Figure 2

(A,B): CT comparison demonstrating regression of abdoinopelvic metastases represented by arrow. Axial views of metastases in October 2019 compared with corresponding axial views demonstrating complete radiographic regression of abdominopelvic metastases in December 2022.