SAN ANTONIO—“In general, this type of response is unheard of in this patient population,” Arul M. Chinnaiyan, MD, PhD, Director of the Michigan Center for Translational Pathology at the University of Michigan and a Howard Hughes Medical Institute Investigator, said during a keynote lecture here at the American Society for Radiation Oncology Annual Meeting, sharing some of the first analyses from the Stand Up To Cancer-Prostate Cancer Foundation Prostate Cancer Dream Team work. The research includes 500 men with metastatic castration-resistant prostate cancer from eight different clinical sites, whose tumors have undergone DNA and RNA sequencing.
The “unheard of response” was that of a man on the study who was found to have homozygous deletion in BRCA2 and amplification of the androgen receptor, who was treated with a PARP inhibitor (to target the BRCA aberration) and abiraterone (to target the androgen receptor amplification). The patient has had “massive tumor regression,” with PSA levels now essentially undetectable (from 127 ng/ML at the time of treatment)—and has had a durable response now for two years since starting this combination treatment.
It bears repeating Chinnaiyan's remark: “This type of response is unheard of in this patient population.”
Although findings like these are promising, there is still a lot of work to do before they become “heard of” on a greater scale for these patients. The information Chinnaiyan shared during the talk was based on analyses of the first 100 men in this study, he said.
In a follow up email interview, Chinnaiyan answered these questions about the goals of the research and when it could be scalable for patients beyond this study.
1. Could you explain what the study is and its goals?
“The study uses whole exome and transcriptome sequencing for metastatic prostate cancers. The goal of the research is to determine the mutational landscape of castration-resistant prostate cancer and identify clinically actionable subsets of patients.
“We have been able to show that we can carry out comprehensive clinical sequencing in a multi-institutional fashion in real-time.”
2. What are some of the key findings about the genomic landscape of these patients that you've found so far? And what do the findings mean for radiation oncologists—your audience for the talk at ASTRO?
“The most clinically relevant results were the somatic and germline aberrations in the DNA repair genes BRCA2, BRCA1, and ATM, found in 23 percent of patients. This [finding] suggests that this subset of metastatic prostate cancer patients may benefit from PARP inhibitors or platinum therapy.
“It will be important to understand the mutational and gene expression blueprint of cancer in order to potentially predict higher sensitivity to radiotherapy. Also when combining other therapies with radiation, it will be important to consider this with the molecular profile in mind.”
3. You touched on this briefly during the talk—is this type of sequencing feasible on a bigger scale across multiple types of cancer centers?
“It would still be challenging to scale the approaches I presented across cancer centers, but I do believe that intermediate-sized panels targeting DNA and RNA may be possible.
“Challenges that remain will be reimbursement for the sequencing assays, as well as the targeted agents that they may suggest. We also need to develop more drugs against cancer targets that have been traditionally considered undruggable.”
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