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 session1709P - Outcomes with novel combinations in non-clear cell renal cell carcinoma (nccRCC): ORACLE studyPresenter: Deepak Kilari Session: Poster session 11 1710P - Exposure-response (E/R) relationship of nivolumab (N) and ipilimumab (I) in patients (pts) with metastatic renal cell clear cell carcinoma (mRCC) from the randomised phase II BIONIKK studyPresenter: Benoit Blanchet Session: Poster session 11 1711P - Real-word data challenging the treatment paradigm in metastatic renal cancer: Time to separate IMDC intermediate / poor risk groups?Presenter: John McGrane Session: Poster session 11 1712P - Real-world efficacy of first-line nivolumab plus ipilimumab and its practical predictive biomarkers in advanced renal cell carcinoma: First analysis from RENOIR study [KCSG GU22-13]Presenter: Jwa Hoon Kim Session: Poster session 11 1713P - A deep learning approach utilizing the electronic health record (EHR) to identify cancer recurrence in renal cell carcinoma (RCC)Presenter: Jue Hou Session: Poster session 11 1714P - Detection and monitoring of translocation renal cell carcinoma via epigenomic profiling of cell-free DNAPresenter: Simon Garinet Session: Poster session 11 1715P - Interim analysis results from a phase II study of adjuvant penpulimab in very high-risk clear cell renal cell carcinomaPresenter: Xu Zhang Session: Poster session 11 1716P - Primary resistance to front-line immune-based combinations in patients with advanced renal cell carcinoma (ARON-1)Presenter: martina catalano 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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