In this interview, Nicholas Vogelzang, MD, speaks with i3 Health about the recent FDA approval of rucaparib (Rubraca®, Clovis Oncology, Inc.) for the treatment of patients with metastatic BRCA-mutated castration-resistant prostate cancer (CRPC) who previously received one line of taxane-based chemotherapy and at least one line of androgen receptor-directed therapy. Dr. Vogelzang, Clinical Professor of Medicine at the University of Nevada School of Medicine and one of the investigators of the TRITON2 trial, on which the approval was based, discusses the challenges of treating patients with metastatic BRCA-mutated CRPC and the benefits that rucaparib has to offer for patients with this disease.
Can you comment on the significance of the approval of rucaparib for patients with BRCA-mutated metastatic CRPC?
Nicholas Vogelzang, MD: Rucaparib is a huge help for the 10% to 15% of patients who have BRCA mutations as drivers for their prostate cancer. I have been routinely testing for both germline and somatic mutations for the last year, and I have accumulated quite a number of patients, so as soon as rucaparib was FDA approved and available, I started treating patients with it the next day.
What are some of the most challenging aspects of treating patients with BRCA-mutated metastatic CRPC?
Dr. Vogelzang: These patients are young, they usually have aggressive disease, and their disease generally accelerates into a lot of pain rather quickly. I tend to use a fair amount of chemotherapy for them, and that can be difficult, so having an approved oral agent is a big plus for them.
Unfortunately, many men with metastatic prostate cancer—perhaps over 90%—have not been genetically tested in the past, so the men who have a BRCA mutation now won't know it. There will be a large scrambling among urologists and medical oncologists to get testing done. That is always a little bit tough, because you have to test either the circulating cell-free DNA—a biopsy that is less than 10 years old, and many of these men had their prostates removed more than 10 years ago—or you have to do a germline test. Rucaparib can be used in men with any of those positive genetic findings.
How do you foresee the treatment of patients with BRCA-mutated metastatic CRPC evolving in the coming years?
Dr. Vogelzang: The duration of response to rucaparib is about a little less than a year, so unfortunately, the drug is not long lasting. An emergence of resistance to rucaparib will be a major new medical challenge, requiring both pharmaceutical development and laboratory work to overcome that anticipated resistance. I've already had patients in TRITON2 whose cancers have become resistant, and it's a real challenge. These patients are young, healthy, and very upbeat about the fact that they got a good result with rucaparib. Then when it stops working, they're quite discouraged and have to start looking for new avenues of therapy. There may be some role for platinum-based agents in those patients in the future.
Do you have any words of advice for community oncologists and other members of the cancer care team treating these patients?
Dr. Vogelzang: Yes, I do: test the tumor. I have a trick that I've been employing in the last six months. Caris Life Sciences®, where I get my somatic testing done, has partnered with a company called Ambry Genetics®. With the same tissue from the prostate biopsies or prostatectomy specimens, you can get both results back from both the genetic germline and the genetic somatic tests. I've found it to be very helpful.
About Dr. Vogelzang
Nicholas Vogelzang, MD, is a Clinical Professor of Medicine at the University of Nevada School of Medicine and a medical oncologist at the Comprehensive Cancer Centers of Nevada. He is also Associate Chair of the Genitourinary Committee for US Oncology Research and Vice Chair of the Southwest Oncology Group (SWOG) Genitourinary Committee. Dr. Vogelzang specializes in the treatment of genitourinary malignancies, including prostate, kidney, bladder, and testicular cancers, as well as lung cancer and mesothelioma. He has published numerous peer-reviewed articles and book chapters, and he has led many clinical trials investigating novel therapeutics for patients with mesothelioma and genitourinary malignancies.
For More Information
Abida W, Campbell D, Patnaik A, et al (2019). Preliminary results from the TRITON2 study of rucaparib in patients (pts) with DNA damage repair (DDR)-deficient metastatic castration-resistant prostate cancer (mCRPC): updated analyses. Ann Oncol (ESMO Congress Abstracts), 30(suppl_5):v327-v328. Abstract 846PD. DOI:10.1093/annonc/mdz248.003
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of i3 Health.