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
4596 - A Phase 2, Open-Label, Randomized, Multicenter Trial of Encorafenib + Binimetinib Evaluating a Standard-dose and a High-dose Regimen in Patients With BRAFV600-Mutant Melanoma Brain Metastasis (MBM) (POLARIS)
Presenter: Michael Davies
Session: Poster Display session 3
Resources:
Abstract
1891 - Continuation of annual screening mammograms and breast-cancer mortality in women over 70
Presenter: Xabier Garcia De Albeniz
Session: Poster Display session 3
Resources:
Abstract
5587 - Introducing standardized medical procedure and dynamic decision support program in precision oncology for the community of practice
Presenter: Istvan Petak
Session: Poster Display session 3
Resources:
Abstract
4757 - Effectively using primary care givers in oncology care through capacity building, task sharing and techno-mentoring.
Presenter: Dinesh Pendharkar
Session: Poster Display session 3
Resources:
Abstract
4497 - A single institution review of capecitabine related acute admissions and cost analysis
Presenter: Gemma Dart
Session: Poster Display session 3
Resources:
Abstract
2187 - Health status of middle-aged and older cancer survivors in China: results from the China Health and Retirement Longitudinal Study (CHARLS)
Presenter: Jiarui Li
Session: Poster Display session 3
Resources:
Abstract
5101 - Crossed looks on lung cancer perception and knowledge from general public and physicians in France: results of a two-fold survey
Presenter: Céline Mascaux
Session: Poster Display session 3
Resources:
Abstract
4354 - Knowledge and perception of clinical trials (CTs) and attitude towards participation among Polish oncological patients - A pilot survey
Presenter: Artur Kotowski
Session: Poster Display session 3
Resources:
Abstract
3499 - Achieving best possible cancer treatment outcomes in care pathways through benchmarking; ABC-Benchmarking
Presenter: Anke Wind
Session: Poster Display session 3
Resources:
Abstract
2270 - Impact of 10-day Fulbright Specialist Program (FSP) and Project Pink Blue (PPB) Education Sessions on Medical Oncology knowledge among Doctors that treat cancer in Nigeria
Presenter: Mike Martin
Session: Poster Display session 3
Resources:
Abstract