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
2600 - Atezolizumab (atezo) vs chemotherapy (chemo) in patients (pts) with platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): a long-term overall survival (OS) and safety update from the Phase III IMvigor211 study
Presenter: Michiel Van der Heijden
Session: Poster Display session 3
Resources:
Abstract
3598 - Three-Year Follow-Up From the Phase 3 KEYNOTE-045 Trial: Pembrolizumab (Pembro) Versus Investigator’s Choice (Paclitaxel, Docetaxel, or Vinflunine) in Recurrent, Advanced Urothelial Cancer (UC)
Presenter: Andrea Necchi
Session: Poster Display session 3
Resources:
Abstract
2382 - First Report of Efficacy and Safety From a Phase 2 Trial of Tislelizumab, an Anti-PD-1 Antibody, for the Treatment of PD-L1+ Locally Advanced or Metastatic Urothelial Carcinoma (UC) in Asian Patients
Presenter: Dingwei Ye
Session: Poster Display session 3
Resources:
Abstract
2388 - Quality of Life of Metastatic Urothelial Cancer (mUC) Patients Treated with Enfortumab Vedotin (EV) Following Platinum-Containing Chemotherapy and a Checkpoint Inhibitor (CPI): Data from EV-201 Cohort 1
Presenter: Bradley McGregor
Session: Poster Display session 3
Resources:
Abstract
3748 - Safety and efficacy of atezolizumab (atezo) in patients (pts) with autoimmune disease (AID): subgroup analysis of the SAUL study in locally advanced/metastatic urinary tract carcinoma
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
1126 - Validation of the VIO prognostic index in patients with metastatic urothelial carcinoma treated with immune-checkpoint inhibitors
Presenter: Rafael Morales Barrera
Session: Poster Display session 3
Resources:
Abstract
3693 - Pathologic outcomes after neoadjuvant chemotherapy for high-risk muscle invasive bladder cancer
Presenter: Justin Matulay
Session: Poster Display session 3
Resources:
Abstract
4840 - Analysis of response to prior therapies and therapies after treatment with erdafitinib in fibroblast growth factor receptor (FGFR)-positive patients (pts) with metastatic urothelial carcinoma (mUC)
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract
1221 - Clinical outcomes by sex with atezolizumab (atezo) monotherapy in patients (pts) with locally advanced/metastatic urothelial carcinoma (mUC)
Presenter: Jean Hoffman-censits
Session: Poster Display session 3
Resources:
Abstract
1715 - National Small Cell Bladder Cancer Audit: Results from 26 UK institutions
Presenter: Caroline Chau
Session: Poster Display session 3
Resources:
Abstract