Additional Advances in Advanced Prostate Cancer With Tanya Dorff, MD

Oncology Data Advisor: Thank you so much for being here today, Dr. Dorff, to talk about your recent involvement in this activity with i3 Health. I wanted to, before we start, ask would you like to introduce yourself and what you research?

Tanya Dorff, MD: Sure. I'm Tanya Dorff. I'm a Genitourinary Medical Oncologist with a research interest and clinical focus on prostate cancer and particularly immunotherapy. I am Section Chief for Genitourinary Cancers at the City of Hope and a fan of genitourinary cancers more broadly as well.

Oncology Data Advisor: Awesome. Well, thank you again and it's good to have you back. First question I have for you today is, since recording this activity with i3 Health, have there been any updates regarding treatment concepts and new data for advanced prostate cancer?

Dr. Dorff: Yes, absolutely. This was a big year for prostate cancer. The big story I would say has been the poly-adenosine diphosphate ribose polymerase (PARP) inhibitor combinations with androgen receptor (AR) pathway inhibitors, so trials like PROpel, MAGNITUDE, and then more recently TALAPRO-2. These have actually led to FDA approvals. This is already impacting patient care potentially. These combinations are for first-line metastatic castration-resistant prostate cancer (mCRPC), and the enzalutamide/talazoparib combination got approved in patients with homologous recombination repair alterations, so it is still a selected population based on next-generation sequencing (NGS). The olaparib and abiraterone combination got approved for BRCA-1 and -2. There is lots of data on that, that's really important and a bit confusing.

The other big story just came out at the European Society of Medical Oncology (ESMO), which is the use of lutetium prostate-specific membrane antigen (PSMA) radioligand therapy in the PSMAfore trial that was presented at ESMO. This was a population of metastatic castration-resistant prostate cancer (mCRPC) before docetaxel. Right now, the FDA approval is post–taxane chemotherapy and that's where we're all using it in our clinics, but the PSMAfore data shows efficacy, not unsurprisingly, in patients before chemotherapy. It won't lead to a label change immediately. It's not something we can implement quite yet in our clinics, but it's something to be aware of because there's certainly been demand for the use of this agent in patients who cannot or have not yet gotten chemotherapy.

Oncology Data Advisor: Incredible. It's definitely exciting to hear about all the updates that have gone on this year. Going into the next question that I had for you, I know you briefly said that it is kind of confusing. In your opinion, why is it important for clinicians to stay up-to-date regarding the treatment landscape of prostate cancer to potentially combat this confusion?

Dr. Dorff: It's hard to keep up when there's so much happening, not only in prostate cancer, but in other solid tumors as well, but it's critical because as we get more options and as they become options that are linked to a selection factor—whether it be NGS or PSMA positron emission tomography (PET) in the case of the radioligand therapy—understanding which patients are going to be best candidates for one approach versus another, knowing what those options are, how they sequence really can make a difference for patients. We're making sure that we try to use our most effective therapies earlier and understanding that what's the most effective therapy might be different for one patient from another.

Oncology Data Advisor: Kind of on the same topic, do you have any further advice for clinicians struggling to maintain this updated understanding being presented for prostate cancer treatment?

Dr. Dorff: Oncologists are really, surprisingly, fantastic about staying up-to-date in this complex world with accelerated development of new therapeutics across the board. I'm sure the National Comprehensive Cancer Network (NCCN) is a familiar resource for all solid tumors, and I will say the prostate group has really tried to update the guidelines frequently enough that new findings that are very impactful and can be implemented in practice right away are addressed as close to real-time as possible. NCCN guidelines can't be updated minute by minute, but they are updated quite frequently, so I think clinicians can rely on that. It's a very well-vetted resource. It is a little bit of a menu, so some of the nuance isn't there, but it does at least provide a summary of options that are with level one evidence. The American Society of Clinical Oncology (ASCO) conferences obviously are a great place because, in addition to seeing the new data, there's usually commentary that helps us contextualize.

Often a good discussant will change my view of the data that were just presented and help me understand what are the limitations and what does it really mean. If we can't get to ASCO conferences, there are some of these "Best of ASCO Conferences" where someone will try to distill it and give a very high-level view as well. Then finally, if you're really interested in genitourinary cancer, there's this great podcast called Uromigos that a lot of us participate in. They do a paper of the month, so if there's a new big study that's presented, the author will be interviewed. Again, that's where you get not only what are the data, but a little bit more of the contextualization. They have some debates sometimes as well, so it can be very timely and topical.

Oncology Data Advisor: Final question I have for you is since recording, have there been any ongoing—I know that you mentioned earlier some of the trials—are there any clinical trials ongoing or in the future involving prostate cancer treatment that you would like to highlight?

Dr. Dorff: Some have reported out, but some haven't yet. We have seen a press release for CONTACT-02, which is cabozantinib plus atezolizumab compared to a control arm of second androgen receptor (AR) pathway inhibitors. This was a big phase 3 trial, reportedly positive. We haven't seen the full data, so that's one to watch out for next year. This might bring us an immune checkpoint inhibitor in combination for a select group of prostate cancer patients. In this case, it's patients with visceral involvement primarily or soft tissue, but not for bone only. There's some nuance and it's going to be important for us to really look at the weeds of the data, the risks and the benefits when they're presented next year. That's definitely a trial that could lead to a new therapeutic option in prostate cancer. The Lutetium PSMA radioligand is, of course, being studied in UpFrontPSMA, metastatic hormone-sensitive; so are PARP inhibitors, so are a number of other targeted therapies.

Those are trials to think about, not only to watch for the results, but consider enrolling your patient if you have one in your geographic region, because that's how we're going to get more options for triplets that are novel beyond just triplet with an AR pathway inhibitor plus or minus chemotherapy with docetaxel. We would all love more options. Then the last one I want to highlight is the androgen receptor degrader, the ARV-110 and the ARV-766. These are really promising agents that are in development. So, a little further off. Same with AMG-509, which just got presented at ESMO. This is an immunotherapy, a bispecific antibody. Some of these agents that are really new and different are showing promising preliminary results, and I would encourage clinicians to look out for those in the future. Again, if you're looking for more options for your patient, see whether you have access for your patient to one of those clinical trials in your area.

Oncology Data Advisor: Thank you for your thorough research in this and providing us with all these amazing resources and stuff to look forward to. Thank you so much, Dr. Dorff, for your involvement and your time today.

Dr. Dorff: My pleasure. Thanks so much.

About Dr. Dorff

Tanya Dorff, MD, is a Professor in the Department of Medical Oncology and Therapeutics Research and serves as Division Chief of the Genitourinary Disease Program at City of Hope. Her research interest spans genitourinary cancers broadly, including prostate, kidney, bladder and penile cancers and immunotherapy development and treatment options. Dr. Dorff is recognized for her research and clinical expertise in prostate cancer internationally.

Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor.