2019 ASCO Annual Meeting!
Session: Genitourinary (Prostate) Cancer
Type: Poster Session
Time: Saturday June 1, 1:15 PM to 4:15 PM
Location: Hall A
Interim results from a phase 2 study of olaparib (without ADT) in men with biochemically-recurrent prostate cancer after prostatectomy, with integrated biomarker analysis.
Genitourinary (Prostate) Cancer
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #157)
J Clin Oncol 37, 2019 (suppl; abstr 5045)
Author(s): Emmanuel S. Antonarakis, Hao Wang, Benjamin A. Teply, William Kevin Kelly, Jamie Willms, Rana Sullivan, Serina King, Catherine Handy Marshall, Tamara L. Lotan; Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Department of Medical Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD; Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, PA; University of Nebraska Medical Center, Omaha, NE; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD; Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD
Background: Pts with biochemically-recurrent (BCR) prostate cancer after local therapy with a PSA doubling time (PSADT) of ≤6 mo are likely to develop metastases and death from their disease. We hypothesized that the PARP inhibitor olaparib would be effective as a non-hormonal therapy for biomarker-unselected pts with BCR after prostatectomy, the first study of PARP inhibition in the hormone-sensitive setting. We report pre-specified interim results from the first stage of the trial. Methods: This investigator-initiated multicenter study (NCT03047135) enrolled pts with non-metastatic BCR after prostatectomy, with a PSADT of ≤6 mo. PSA had to be ≥1.0 ng/mL, with T ≥150 ng/dL. Pts received olaparib 300 mg twice daily (without ADT), until a doubling of their PSA or metastatic progression. The primary endpoint was confirmed ≥50% PSA decline (PSA50 response). Secondary endpoints included safety, minor PSA response (1-50% reduction), and PSA progression-free survival. Integrated biomarker analyses included somatic DNA sequencing, RNA expression analysis and IHC for DNA damage markers, using prostatectomy specimens. The study was designed to enroll a biomarker-unselected population using a staged-adaptive design, with up to 50 pts. In the first stage, ≥3 PSA50 responses out of 20 pts were required to proceed to the second stage; otherwise enrichment with biomarker-selected pts would occur. Results: Between 5/2017 and 11/2018, 20 men (median age, 65) enrolled in the first stage, with a median follow-up of 6 (range, 3-16) mo. Median PSADT was 3.1 mo, and 55% had Gleason ≥8 cancers. Seven men (35%) had BRCA2/ATM mutations. Three men (15%) had PSA50 responses (all had BRCA2 muts – 2 had complete PSA responses), and 4 other men (20%) had minor PSA responses. Median PSA progression-free survival was greater in men with vs. without BRCA2/ATM muts (9 vs. 4 mo; P= 0.02). Common toxicities of olaparib included fatigue, nausea, anemia and leukopenia; 2 men required a dose reduction. Conclusions: Olaparib (without ADT) was tolerable and showed activity in hormone-sensitive BCR prostate cancer, especially in men with BRCA2 muts. Second-stage enrolment is ongoing. Clinical trial information: NCT03047135