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 session1687P - Perceptions of genetic testing and lived experiences in women with locally advanced or metastatic ovarian cancer: A focus on BRCAm and BRCAwt patientsPresenter: María Jesús Rubio Pérez Session: Poster session 11 1688P - Psychosocial distress and spirituality among elderly patients with cancer in NigeriaPresenter: Zainab Ogunjimi Session: Poster session 11 1689TiP - The social stigma of smokers and patients with lung cancer: Detection of phoenomenon and testing of EMDR (eye movement desensitization and reprocessing) interventionPresenter: Domenico Galetta Session: Poster session 11 1692P - A phase Ib/IIa trial to evaluate the safety and efficacy of PM8002/ BNT327, a bispecific antibody targeting PD-L1 and VEGF-A, as a monotherapy in patients with advanced renal cell carcinomaPresenter: Xinan Sheng Session: Poster session 11 1693P - CaboPoint: Final results from a phase II study of cabozantinib after checkpoint inhibitor (CPI) combinations in patients with advanced renal cell carcinoma (aRCC)Presenter: Laurence Albiges Session: Poster session 11 1695P - Phase I LITESPARK-018: Dose escalation study of belzutifan in advanced pretreated clear cell renal cell carcinoma (ccRCC)Presenter: Ulka Vaishampayan Session: Poster session 11 1696P - A phase I/ II trial of pazopanib (Paz) alternating (alt) with bevacizumab (Bev) in treatment-naïve metastatic clear cell renal cell carcinoma (mccRCC) patients (pts): Phase II resultsPresenter: Saby George Session: Poster session 11 1697P - Phase II randomized double-blind trial of axitinib (Axi) +/- PF 04518600, an OX40 antibody (PFOX) after PD1/PDL1 antibody (IO) therapy (Tx) in metastatic renal cell carcinoma (mRCC): Final analysisPresenter: Sarmad Sadeghi Session: Poster session 11 1698P - Avelumab + axitinib (Ave + Axi) vs sunitinib (Sun) in advanced renal cell carcinoma (aRCC): Final analysis of patient (pt)-reported outcomes (PROs) and quality-adjusted time without symptoms or toxicity (Q-TWiST)Presenter: Balaji Venugopal 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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