This abstract provides data on 157 patients with targeted exome sequencing of biopsies. Patients with pure small cell histology were excluded in the final analysis. The primary outcome was time from therapy to clinical or radiographic progression. Therapy was divided into two groups – group NHT was “next generation hormonal therapy” (abiraterone or enzalutamide) and group D was docetaxel. In terms of the biomarkers, DDR gene loss was defined as biallelic loss and tumor suppressor gene alterations were defined by both monoallelic and biallelic.
The median overall survival for the entire group was 4.5 years from the time of mCRPC designation from the original abstract. Genes of interest included PTEN, TP53, RB1, BRCA2, ATM, AR amplification, and AR mutation. The NHT group as a whole had a median time to treatment failure of 12.2 months and the median time to treatment failure (TTTF) of docetaxel was 5.1 months.
Based on the gene alterations, PTEN and TP53 alone did not affect TTTF or overall survival. RB1 biallelic loss predicts shorter TTTF for both therapies. AR amplification did not change the TTTF on ABI or ENZA, but AR mutations appeared to confer benefit for patients treated with abiraterone or enzalutamide.
On the original abstract, the authors created a 0 to 2 scoring system, with one point earned for PTEN loss and one point earned for biallelic RB 1 loss. For patients with 0 points, the median TTTF was 14.7 months, vs 12 months for those with 1 point, and 3.8 months for those with 3 points. Updated date presented on the poster shows that patients with a combination of RB1+PTEN loss had worse time TTTF as well as patients with RB1 and TP53 loss.
This exploratory analysis found biallelic RB1 loss is present in 12% of tumors and these patients have a shorter TTTF with either hormonal therapy or chemotherapy. If patients also had an additional PTEN or TP53 loss, this would worsen prognosis and survival. It is unclear what the sequencing of therapies was for these patients, as many patients received both NHT and docetaxel and this sequencing may impact the TTTF. Regardless, this analysis is thought-provoking and future studies should prospectively incorporate genomic biomarker analysis so we can better identify which therapies are most beneficial for our patients at the right time.
Presented by: Anis Hamid, MBBS, Medical Oncologist, Melbourne Australia, GU Oncology Research Fellow, Dana-Farber Cancer Institute Boston, Massachusetts
Written by: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, @TheRealJasonZhu at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA
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