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 session1699P - Impact of Latino ethnicity on the gut microbiome and response to immune checkpoint inhibition (ICI) with CBM588 in patients (pts) with metastatic renal cell cancer (mRCC)Presenter: Regina Barragan-Carrillo Session: Poster session 11 1700P - Impact of sarcomatoid (S) and rhabdoid (R) components (comp.) on the efficacy of nivolumab (N) +/- ipilimumab (I) in the first-line (L1) treatment of metastatic clear cell renal cell carcinoma (mRCC) in the randomized phase II BIONIKK trialPresenter: Yann-Alexandre Vano Session: Poster session 11 1701P - NEOTAX: A phase II trial of neoadjuvant toripalimab plus axitinib for clear cell renal cell carcinoma with inferior vena cava tumor thrombusPresenter: Liangyou Gu Session: Poster session 11 1702P - Updated results of phase II study of cabozantinib (Cabo) with nivolumab (Nivo) and ipilimumab (Ipi) in advanced renal cell carcinoma with divergent histologies (RCCdh)Presenter: Bradley McGregor Session: Poster session 11 1703P - Updated overall survival in patients with prior checkpoint inhibitor (CPI) therapy in the phase III TIVO-3 studyPresenter: Miguel Zugman Session: Poster session 11 1704P - Potential surrogate endpoints for overall survival (OS) in immunotherapy (IO)-treated metastatic renal cell carcinoma (mRCC): An International Metastatic Database Consortium (IMDC) studyPresenter: Renee Saliby Session: Poster session 11 1705P - Association between baseline radiological tumor burden (BRTB) and outcomes in metastatic clear cell renal cell carcinoma (mccRCC) treated with first line (1L) immunotherapy (IO)-based regimensPresenter: Rashad Nawfal Session: Poster session 11 1707P - A plasma proteomic based algorithm is associated with prognosis in renal cell carcinomaPresenter: Eddy Saad Session: Poster session 11 1708P - The clinical value of tumor-informed minimal residual disease detection in renal cell carcinomaPresenter: linhui wang 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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