Abstract 1213P
Background
Metastatic prostate cancer (mPC) is the second most common cancer in men globally. Identifying actionable genetic alterations is of increasing importance when looking for sensitivity to PARP inhibitors, targeted therapies and immune checkpoint inhibitors. Furthermore, certain alterations may predict sensitivity to standard chemotherapy and hormonal agents and can aid treatment planning.
Methods
Metastatic prostate cancer patients that underwent somatic DNA next generation sequencing analysis for 395 cancer-related genes (Foundation Medicine®) were collated prospectively. Identified variants were categorized as actionable, potentially actionable and not actionable using OncoKB precision oncology knowledge base for available compounds and PubMed and clinicaltrials.gov for investigational agents in early phase clinical studies.
Results
36 patients were analysed - 26 samples were prostate tissue,2 lymph node, 1 bone and 7 peripheral blood samples. All patients had at least one alteration, with median of 3. Alterations were identified in 219 genes. Of the 36 patients with sequencing results, 26 (72%) had actionable or potentially actionable alterations and the remainder had alterations in genes with no known therapeutic approach (22%). Of those with at least potentially actionable alterations, the most frequently occurring included PTEN (25%), TMPRSS (36%), BRCA2 (13.8%) and ATM (13.8%). As regards potential therapeutic options, 57% of patients had mutations suggesting sensitivity to DNA damage repair pathway inhibitors, 65% had alterations that could be targeted by precision inhibitors and 4% had alterations that may predict sensitivity to immunotherapeutic agents.
Conclusions
Prostate cancer harbours a wide array of both actionable and potentially actionable alterations that offer alternative treatment strategies for patients. Recent and evolving clinical trials show deep and durable responses to these novel agents in mPC. Identifying pathogenic variants could potentially have led to further treatment options in 72% of our series, although many agents are not accessible outside of clinical trials.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Cork University Hospital.
Funding
Has not received any funding.
Disclosure
D. Collins: Honoraria (self): Pfizer; Honoraria (self), Travel/Accommodation/Expenses: Genmab; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses: Eli Lilly; Honoraria (self), Travel/Accommodation/Expenses: F. Hoffmann-La Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy: Seattle Genetics. R. Bambury: Advisory/Consultancy: Bayer Janssen; Advisory/Consultancy: F. Hoffmann-La Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Abbvie; Travel/Accommodation/Expenses: Ipsen; Officer/Board of Directors: Portable Medical Technology. All other authors have declared no conflicts of interest.