Abstract 3742
Background
Loss of tumour suppressor genes (TSGs), TP53, PTEN and Rb are common in advanced prostate cancer. They are associated with worse outcomes in hormone-resistant prostate cancer. However, the prognostic value of TSGs loss in metastatic hormone-sensitive prostate cancer (mHSPC) is unknown. Therefore we sought to evaluate the prognostic value of TSGs loss on progression-free survival (PFS) in mHSPC.
Methods
We performed a retrospective analysis of patients with mHSPC treated at Mayo Clinic Arizona between 2015 and 2018. Clinical characteristics, first-line treatment, and TSGs alterations were recorded. TSG-altered (TSG-alt) was defined as an alteration in ≥ 1 TSG (TP53, PTEN or Rb). Demographics and clinical characteristics were compared between groups by chi-square test for frequency data or Kruskal Wallis rank-sum test for continuous measures. PFS was estimated based on the Kaplan-Meier method and compared between groups by the log-rank test.
Results
59 patients with mHSPC were included. 41 (69%) patients received first-line treatment with abiraterone and 18 (31%) patients with docetaxel. 32 patients (54%) had TSG-alt. 20 patients (39%) had damage to 1 TSG, 11 patients (19%) had damage to 2 TSGs, and 1 patient had damage to all 3. Clinical characteristics, prior locoregional treatment, and metastatic disease on diagnosis were similar between TSG-alt and TSG-normal groups. The rate of damaging alterations to the genes was: TP53 21 patients (35.6%), PTEN 21 patients (35.6%), and Rb 3 patients (5.1%). Median PFS was 33.2 mos (95% CI 23.1-NE) for TSG-normal versus 19.7 mos (95% CI 14.4-30.0) for TSG-alt, p = 0.005. There was no difference in PFS between having 1 TSG alteration (18.4 mos; 95% CI 14.7 - NE) vs ≥ 2 TSG alterations (21.8 mos; 95% CI 10.6 - NE) or between first-line treatments with abiraterone (20.2 mos; 95% CI 14.7-35.1) vs docetaxel (19.6 mos; 95% CI 8.0 - NE) in those with TSG-alt.
Conclusions
Loss of TSGs function is common in patients with mHSPC, and is prognostic for early progression during first-line treatment. The presence of ≥ 1 TSG-alt indicates an adverse prognostic impact in mHSPC. Confirmation of these findings may establish the need for inclusion of molecular stratification when defining high risk mHSPC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Mayo Clinic Cancer Center.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5007 - Functional systemic CD4 immunity is required for clinical responses to PD-L1/PD-1 blockade therapy
Presenter: Miren Zuazo
Session: Poster Display session 3
Resources:
Abstract
5760 - Landscape of PD-L1 expression status in Chinese solid tumor patients.
Presenter: Yi Zhong
Session: Poster Display session 3
Resources:
Abstract
3733 - Anti-cancer and immunomodulatory effects of cobimetinib in triple negative breast cancer
Presenter: Chun-Yu Liu
Session: Poster Display session 3
Resources:
Abstract
4426 - Differential expression of immunoregulatory molecules and highly-associated cancer genes may provide novel insights into strategic trial design for therapeutics
Presenter: Jacob Adashek
Session: Poster Display session 3
Resources:
Abstract
2752 - Insights into the Tumor Immune Microenvironment using Tissue Phenomics to Drive Cancer Immunotherapy
Presenter: Martin Groher
Session: Poster Display session 3
Resources:
Abstract
5713 - Immune competent somatic mosaic model of colorectal cancer
Presenter: Stefania Napolitano
Session: Poster Display session 3
Resources:
Abstract
1898 - Genomic correlates of response to anti-PDL1 Atezolizumab in non-small-cell lung cancer OAK and POPLAR trials
Presenter: Hari Singhal
Session: Poster Display session 3
Resources:
Abstract
3246 - Erdafitinib (erda) versus available therapies in advanced urothelial cancer: A matching adjusted indirect comparison
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
3311 - High level of activity of Nivolumab anti-PD-1 immunotherapy and favorable outcome in metastatic/refractory MSI-H non-colorectal cancer: Results of the MSI cohort from the French AcSé program
Presenter: Christophe Tournigand
Session: Poster Display session 3
Resources:
Abstract
2314 - TP53 and ATM Co-mutation Predicts Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer
Presenter: Yu Chen
Session: Poster Display session 3
Resources:
Abstract