Can we define tumors that will respond to PARP inhibitors? A phase II correlative study of olaparib in advanced serous ovarian cancer and triple-negative breast cancer.
2010; Lippincott Williams & Wilkins; Volume: 28; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2010.28.15_suppl.3002
ISSN1527-7755
AutoresKaren A. Gelmon, Hal W. Hirte, A. Robidoux, K. Tonkin, M Tischkowitz, K. Swenerton, David Huntsman, J. Carmichael, Euan Macpherson, Amit M. Oza,
Tópico(s)BRCA gene mutations in cancer
Resumo3002 Background: Olaparib is a PARP inhibitor (PARPi) which has reported encouraging response data in BRCA mutation carriers. We have completed a phase II translational study evaluating tumor response with serial tumor biopsies to determine markers of response. Methods: Eligible women with advanced breast (BC) or ovarian cancer (OC) were enrolled in 4 cohorts. A Simon 2 stage design was used for 2 cohorts of BRCA mutation negative or unknown patients (pts) with either high grade serous OC (Arm A) or triple negative BC (Arm B). Two other cohorts are reference groups with recurrent OC (Arm C) or BC (Arm D) with identified BRCA mutations. All (pts) had tumor biopsies prior to treatment, after 2 cycles and at progression to assess PARPi activity, loss of heterozygosity (LOH), mutational changes, BRCA1/2 expression, and markers of response including deep sequencing. CT/MRI assessments were done prior to treatment and every 2 cycles. Selected pts had PET scans. Pts were treated with single agent olaparib 400 mg bid on a continuous basis in 4 week cycles. Results: 91 evaluable pts were enrolled. Arm A enrolled 55 pts after evidence of response(s) in the first 15 pts. Arm B did not meet continuation criteria and closed at 15 pts. Arms C and D enrolled predetermined numbers of 10 and 11 pts. Preliminary results show 3 partial responses in Arm C with 6 pts in Arms C and D continuing on treatment at this time. In arm A, 20 of 55 measurable pts remain on treatment with 22+ pts receiving ≥6 cycles of olaparib. Confirmed radiological PRs have been observed in 8 pts with GCIG CA125 response criteria in 14 pts and 142 biopsies collected overall. Conclusions: This is the first trial demonstrating significant evidence of single agent activity of olaparib in women with high grade serous OC. Updated translational study data and response data in BRCA+ and BRCA− tumors will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca AstraZeneca AstraZeneca
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