Treatment with olaparib in a patient with PTEN-deficient endometrioid endometrial cancer

Martin D. Forster, Konstantin J. Dedes, Shahneen Sandhu, Sophia Frentzas, Rebecca Kristeleit, Alan Ashworth, Christopher J. Poole, Britta Weigelt, Stan B. Kaye, L. Rhoda Molife

Research output: Contribution to journalArticleOtherpeer-review

93 Citations (Scopus)

Abstract

Background. A 58-year-old woman presented with metastatic endometrioid endometrial adenocarcinoma after being previously treated with surgery and adjuvant radiotherapy for early-stage endometrial cancer. She had received several lines of chemotherapy for multiple relapses over 9 years and displayed a profound sensitivity to platinum-containing regimens.Investigation. CT scans demonstrated progressing liver, lung and peritoneal metastases and MRI detected multiple intracerebral metastases.Diagnosis. New brain metastases secondary to progressive endometrioid endometrial carcinoma.Management. On the basis of her sensitivity to repeated platinum treatment she was treated with the oral poly(ADP)-ribose polymerase (PARP) 1 inhibitor olaparib as part of a phase I trial. Repeat MRI scan at week 10 of treatment showed a significant reduction in the size of the brain metastases without steroid treatment or radiotherapy and the patient reported subjective improvement in tumor-related symptoms. After 8 months of olaparib treatment the patient developed objective disease progression. The tumor biopsy was negative for somatic BRCA1 and BRCA2 mutations, but displayed loss of PTEN, which has been suggested to be another predictive marker for sensitivity to PARP inhibitors. The patient remained alive for 10 months after completing olaparib, having gone on to derive further clinical benefit from repeat exposure to platinum-based therapy.

Original languageEnglish
Pages (from-to)302-306
Number of pages5
JournalNature Reviews Clinical Oncology
Volume8
Issue number5
DOIs
Publication statusPublished - 1 May 2011
Externally publishedYes

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