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Olaparib is effective for recurrent urothelial carcinoma with BRCA2 pathogenic germline mutation: first report on olaparib response in recurrent UC.

ABSTRACT: Urothelial carcinoma (UC) is a common malignancy of the lower and upper urinary tract. Recurrent UC has poor prognosis due to delayed diagnosis and a lack of clinical management guidance, especially for upper urinary tract UC. Patients with germline or somatic BRCA1/2 mutations are a special population in UC. No evidence is available so far on the effectiveness of poly ADP-ribose polymerase inhibitor (PARPi) in this population. Here, we report a 60-year-old female patient diagnosed with left ureter high-grade UC. Recurrent lesions were found 20?months after radical surgery. Computed tomography (CT) examination showed a slightly high-density soft tissue mass (3.2?×?3.1?cm) on the left posterior wall of the abdomen (waist), soft tissue mass adjacent to the left inner wall of the pelvis (3.2?×?4.2?cm), and multiple enlarged lymph nodes to the left of abdominal aorta. A next-generation sequencing (NGS)-based 605-gene panel detected a novel BRCA2 pathogenic germline mutation c.1670T>A (p.L557*), and a series of somatic insertion and deletion (INDEL) mutations of BRCA1, RB1, and JAK2, and single nucleotide variation (SNV) mutations of TP53, KMT2D, MET, ROS1, and IL7R. The above lesions were reduced significantly or disappeared (partial response, PR) after a 3-month Olaparib treatment, and the patient's general condition remained well. In conclusion, this study proved for the first time that PARPi was effective for UC treatment in patients carrying germline BRCA2 pathogenic mutations, providing new treatment options for such patients. In addition, the circulating tumor DNA (ctDNA) test can be used for drug selection and response monitoring in UC treatment.

SUBMITTER: Yang H

PROVIDER: S-EPMC7675892 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Olaparib is effective for recurrent urothelial carcinoma with BRCA2 pathogenic germline mutation: first report on olaparib response in recurrent UC.

Yang Hong H Liu Zhimin Z Wang Yufang Y Li Jun J Li Ruiqian R Wang Qilin Q Hu Chen C Jiang Haiyang H Wu Hongyi H Song Lele L Bai Yu Y

Therapeutic advances in medical oncology 20201111

Urothelial carcinoma (UC) is a common malignancy of the lower and upper urinary tract. Recurrent UC has poor prognosis due to delayed diagnosis and a lack of clinical management guidance, especially for upper urinary tract UC. Patients with germline or somatic BRCA1/2 mutations are a special population in UC. No evidence is available so far on the effectiveness of poly ADP-ribose polymerase inhibitor (PARPi) in this population. Here, we report a 60-year-old female patient diagnosed with left ure ...[more]

PMID: 33240400

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Project description:RATIONALE:Pancreatic cancer (PC) is considered as one of the deadliest cancers all over the world. Germline and somatic BRCA1/2 mutations have been widely studied in breast and ovarian carcinomas as they have been found to enhance the risk for disease progression. Olaparib, an oral poly(adenosine diphosphate-ribose)polymerase (PARP) inhibitor, has been approved for the treatment strategy of ovarian cancer with any BRCA1/2 mutations. There is a lack of studies which focus on the treatment of other cancer with BRCA-Mutation. PATIENT CONCERNS:This report describes a patient whose presenting complaints were "Physical examination showed that the pancreas was occupied for one month." He initially was diagnosed with stage IV PC based on conventional imaging and pathologic assessment. He had a known germline BRCA 2 mutation, which exhibited a good response to PARP inhibitor therapy. DIAGNOSIS:Through the biopsy histopathological examination, imaging examination, and genetic testing, the patient was diagnosed as metastatic PC with BRCA2 mutation. INTERVENTIONS:He received gemcitabine and albumin-bound paclitaxel chemotherapy from March 15, 2017 to June 30, 2017, and Nivolumab immunotherapy as the maintenance therapy. After serum CA-199 level increased, Olaparib was orally administered from August 17, 2017 to March. After tumor relapsed, he received multiple lines of chemotherapy, including Trametinib Oxaliplatin, S-1, bevacizumab, and irinotecan liposome injection till July 17, 2018. OUTCOMES:We observed the patient had a good progression-free survival (7.4 months); the lesion of the pancreas was classified as partial disease through Olaparib treatment, which indicated significant shrinkage. But it is difficult to conclude whether such therapy could help prolong the overall survival for such patients. LESSONS:The targeted therapy Olaparib showed early signs of potential in treating PC in patients with mutations of the BRCA genes. With emerging therapeutic modalities and next-generation sequencing development, it is increasingly relevant to consider mutation screenings of patients with PC.

Dataset Information

Olaparib is effective for recurrent urothelial carcinoma with BRCA2 pathogenic germline mutation: first report on olaparib response in recurrent UC.

Publications

Olaparib is effective for recurrent urothelial carcinoma with BRCA2 pathogenic germline mutation: first report on olaparib response in recurrent UC.

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