Abstract 1643P
Background
Compound alterations in TP53, RB1, and/or PTEN have been correlated with poor outcomes in pts with mPC; however, there is limited data regarding whether PTEN alterations(alt) by next generation sequencing (NGS) are prognostic in isolation. PTEN -null de novo mPC is currently being investigated in CAPItello-281 and may represent a clinically actionable subtype. As such, we sought to characterize outcomes of this genomically defined subgroup.
Methods
PROMISE is a multi-institutional database including mPC pts (N=2027) with NGS. Using PROMISE, we analyzed outcomes based on PTEN status in de novo mPC pts.
Results
Among 1036 pts with de novo mPC, 212 (20%) had PTEN alt by NGS. Median age at diagnosis was 64 yrs, 21% were Black, 53% had high volume (HV) disease. Compared to the PTEN-wildtype (wt) group, PTEN-altered mPC had higher co-occurrence of TP53 and/or RB1 mutations (57% vs 37%); lower median PSA (38 vs 63 ng/ml); and more visceral disease (18 vs 11%). Groups were otherwise similar. The table shows univariate (UVA) outcomes based on PTEN status. Outcomes were similar in men with high volume disease on UVA. On multivariable analysis controlling for clinical prognostic features and TP53/RB1 alterations, PTEN status remained independently associated with overall survival (OS) [HR 1.27, 95% CI (0.99, 1.63) p=0.05]. Table: 1643P
| PTEN -alt | PTEN -wt | P value | HR (95% CI) | |
| Median OS, mo (95% CI) | ||||
| Entire cohort | 48.7 (45.3 - 57.5) | 65.4 (60.0 - 72.6) | 0.003 | 0.73 (0.59 - 0.90) |
| LV (n=418) | 52.5 (45.3 - 81.5) | 79.1 (72.1 - 95.8) | 0.002 | 0.60 (0.44 - 0.83) |
| TP53/RB1 null * | 46.1 (34.5 - 56.1) | 56.1(44.7-65.5) | 0.063 | 0.70 (0.48 - 1.02) |
| wt * | 51.6 (47.0 - 79.8) | 72.6 (64.0 − 80.6) | ConclusionsPTEN status correlated with poor outcomes in de novo mPC independent of other clinical and genomic factors. Clinical trial identificationEditorial acknowledgementLegal entity responsible for the studyThe authors. FundingAstraZeneca. DisclosureD. Kilari: Financial Interests, Personal, Invited Speaker: Janssen, Pfizer, Aveo oncology, Seagen, MJH - Life Sciences, Binaytara Foundation; Financial Interests, Personal, Advisory Board: Exelixis, Eisai; Financial Interests, Institutional, Coordinating PI: Exelixis, Genentech. All other authors have declared no conflicts of interest. Resources from the same session1647P - Clinical validity of plasma DNA testing to identify BRCA-mutated (BRCA+) patients in the MAGNITUDE studyPresenter: Gerhardt Attard Session: Poster session 11 1649P - Impact of concomitant medications on safety in patients with high-volume metastatic hormone-sensitive prostate cancer (mHSPC) receiving rezvilutamide (Rez) plus androgen-deprivation therapy (ADT): A post-hoc analysis of the randomized phase III CHART trialPresenter: Dingwei Ye Session: Poster session 11 1650P - Fuzuloparib plus abiraterone acetate and prednisone (AA-P) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): A phase I studyPresenter: Tao Dai Session: Poster session 11 1651P - Characteristics, tolerance and effectiveness of patients aged more or less than 75 years treated with [177Lu]Lu-PSMA-617 as part of France’s early access programPresenter: David Tonnelet Session: Poster session 11 1652P - SAABR: Single arm phase II study of androgen receptor pathway inhibitor (ARPI) + atezolizumab + GnRH analog (ADT) and stereotactic body radiotherapy (SBRT) to the prostate in men with de novo hormone-sensitive metastatic prostate cancer (mHSPC)Presenter: Dana Rathkopf Session: Poster session 11 1653P - Molecular and immunologic correlates of high PSMA/FOLH1 mRNA expression in prostate cancer (PC)Presenter: Rana McKay Session: Poster session 11 1654P - TAMARACK: Randomized Phase II trial of the B7-H3 targeting antibody drug conjugate (ADC) vobramitamab duocarmazine (vobra duo) in metastatic castration-resistant prostate cancer (mCRPC)Presenter: Johann de Bono Session: Poster session 11 1655P - Association of location of BRCA1/2 pathogenic variants with benefit from PARP-inhibitors in metastatic castration-resistant prostate cancers: Results from the PROGRESS studyPresenter: Lorena Incorvaia Session: Poster session 11 1656TiP - The STAMPEDE2 niraparib-abiraterone acetate + prednisolone trial: A phase III, randomised, open-label trial in patients with metastatic prostate cancer (mPC) with a deleterious alteration in a homologous recombination repair (HRR) gene starting androgen deprivation therapy (ADT)Presenter: Sarah Howlett 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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