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 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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