Phase I/Ib study of olaparib and carboplatin in women with triple negative breast cancer

Jung Min Lee*, John L. Hays, Victoria L. Chiou, Christina M. Annunziata, Elizabeth M. Swisher, Maria I. Harrell, Minshu Yu, Nicolas Gordon, Tristan M. Sissung, Jiuping Ji, William D. Figg, Lori Minasian, Stanley Lipkowitz, Bradford J. Wood, James Doroshow, Elise C. Kohn

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

PURPOSE: To investigate the safety, activity, and potential biomarkers of response to olaparib and carboplatin combination in sporadic triple negative breast cancer (TNBC). EXPERIMENTAL DESIGN: Metastatic or recurrent TNBC patients with no germline BRCA mutation or with BRCAPro scores < 10% and a negative family history were eligible. A 3+3 dose escalation tested olaparib capsules (400mg bid, days1-7) with carboplatin AUC3-5 on day1 or 2 every 21 days, ≤ 8 cycles, with olaparib 400mg bid maintenance. Peripheral blood mononuclear cells were collected for polymorphisms and PAR levels, and paired tumor biopsies (pre-/post-cycle 1) for proteomics and apoptosis endpoints. RESULTS: 28 women were treated (median 5 prior regimens [0-12]). Doselimiting toxicity was thrombocytopenia, and symptomatic hyponatremia with carboplatin AUC5. The maximum tolerated dose was olaparib 400mg bid+carboplatin AUC4. Grade 3 and 4 adverse events included neutropenia (36%), thrombocytopenia (11%), and anemia (11%). Responses included 1 complete response (CR; 69+months) and 5/27 partial responses (19%; median 4months [4-7]), for a response rate of 22%. Biomarker findings did not correlate with response. The long-term CR patient with prior negative BRCA testing was found to have deletion of BRCA1 exons1-2. CONCLUSIONS: The olaparib/carboplatin combination is tolerable and has modest activity in sporadic TNBC patients. Further evaluation of predictive biomarkers to identify those with BRCA wild type who had response is warranted.

Original languageEnglish
Pages (from-to)79175-79187
Number of pages13
JournalOncotarget
Volume8
Issue number45
DOIs
StatePublished - 2017
Externally publishedYes

Keywords

  • Carboplatin
  • Olaparib
  • Triple negative breast cancer

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