Abstract 1617P
Background
We determined the performance of a multi-gene copy number variation (CNV) risk score in tissue and plasma cell-free DNA (cfDNA) biospecimens obtained in treatment- naïve metastatic castrate-resistant prostate cancer (mCRPC) patients to predict survival outcomes.
Methods
Metastatic tissue and cfDNA biospecimen sequencing results for CNV gains in AR, MYC, COL22A1, PIK3CA, PIK3CB, NOTCH1 and losses in TMPRSS2, NCOR1, ZPTB18, TP53, NKX3-1 from three independent treatment-naïve mCRPC cohorts (dbGaP, SU2C/PCF and the Vancouver Prostate Centre-University of British Columbia-VPC/BC) were used to to calculate a multi-gene weighted CNV risk score in all cohorts. Survival outcomes included overall survival (OS) and progression free survival (PFS) to first-line abiraterone-acetate/prednisone (AA/P) or enzalutamide (E) therapies adminsitered as mCRPC treatment in a specific cohort. The range of the risk scores obtained in each cohort was dichotomized at the median into a “high-risk” score (above median) and “low-risk” score (below median) and association with OS/PFS performed. Univariate and multi-variate Cox Proportional Hazard Regressions were applied for survival analyses (P<0.05 for significance).
Results
Of 1137 metastatic tissue-cfDNA biospecimens, 662/1137 were treatment-naive for mCRPC therapies and 311 were matched metastatic tissue - cfDNA pairs. The table summarizes results of comparisons between “high” and “low-risk” scores and survivals in each cohort. Pts with high-risk scores derived from metastatic tissue or cfDNA in all cohorts at the univariate and multi-variate level had the shortest OS. High risk scores also had shorter time to response to first-line AA/P and E therapies. Table: 1617P
Risk-score based survival in each independent cohort
| Range of CNV risk score in the cohort(Median) | Number of high risk vs low risk patients (pts) per cohort(N) | Median OS for high vs low risk (Months)(P-value) | Median PFS for high vs low risk scores for AA/P or E (Months)(P-value) | |
| dbGaP metastatic tissue cohort (N=68) | -0.11 to 4.01 (0.37) | 30 vs 38 | 24.9 vs 30.6 P=0.039 | For AA/P 7.8 vs 14 (P=0.0064) |
| SU2C/PCF metastatic tissue cohort (N=98) | -0.35 to 4.11 (2.23) | 49 vs 49 | 22.2 vs 33.7 P=0.003 | Not applicable |
| VPC/BC cfDNA cohort (N=311) | 0 - 9.4 (0) | First-line AA/P (N=137 pts) 51 vs 86 First-line E (N=174 pts)71 vs 103 | 15.5 vs 38.8 PConclusionsA multi-gene CNV risk score predicts survival outcomes and therapy responses to first-line AA/P and E in treatment-naive mCRPC patients and can be used for designing future enrichment type clinical trials. Clinical trial identificationPROMOTE (Prostate Cancer Medically-Optimized Genome-Enhanced Therapy), NCT01953640. Editorial acknowledgementLegal entity responsible for the studyManish Kohli. FundingHas not received any funding. DisclosureM. Kohli: Non-Financial Interests, Personal, Non remunerated activity, Travel only: Triomics Inc.; Non-Financial Interests, Personal, Non remunerated activity, Non-compensated: Nferene Inc. C. Maurice-Dror: Financial Interests, Personal, Financially compensated role, Advisory board/Honoraria/Travel: Jansen, Merck; Financial Interests, Personal, Financially compensated role, Honoraria/Travel: Pfizer; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Financially compensated role: Biomica. A.W. Wyatt: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Pfizer, Merck, Janssen, EMD Serono; Financial Interests, Institutional, Research Funding: ESSA Pharma, Tyra Biosciences. B. Schmidt: Financial Interests, Personal, Advisory Board: ImmunityBio. All other authors have declared no conflicts of interest. Resources from the same session1667P - Psychological issues and neurocognitive functioning in long-term advanced cancer survivors treated with immune checkpoint blockadePresenter: Nathalie Vanlaer Session: Poster session 11 1668P - Unaddressed distress in cancer patients and primary care giver: A cross-sectional comparative study at a Quaternary Government InstitutePresenter: Niharika Bisht Session: Poster session 11 1669P - The burden of shame and guilt: Quality of life in patients with cervical intraepithelial neoplasia (CIN) and cervical cancer – A preliminary studyPresenter: Bar Levy Session: Poster session 11 1670P - Fear of cancer recurrence and its predictors in lymphoma patients and their family caregivers: A cross-sectional studyPresenter: Taha Koray Sahin Session: Poster session 11 1671P - Impact of online delivery of potentially sensitive test results on patients with breast cancer's emotional healthPresenter: Anezka Ferrari Session: Poster session 11 1672P - Living the waiting: Feelings and experiences data from cancer patients in the waiting roomPresenter: Claudia Mosillo Session: Poster session 11 1673P - Medical oncologists with imposter syndrome suffer from burnoutPresenter: Ali Alkan Session: Poster session 11 1674P - Assessment of sexuality in patients with nasopharyngeal carcinomaPresenter: chraa fatima zahra Session: Poster session 11 1675P - Impact of adjuvant hormonal therapy on sexual and global quality of life in young egyptian women with breast cancerPresenter: Omnia Korani Session: Poster session 11 1676P - Sexuality among Tunisian breast cancer survivorsPresenter: Nefzi Issaad Session: Poster session 11 This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used. For more detailed information on the cookies we use, please check our Privacy Policy.
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