Choosing AR-Targeted Therapy in CSPC

Treating mCSPC with Anti-Androgen Therapy and Monitoring for Progression

During a live virtual event, Roby A. Thomas, MD, discussed the tolerability of androgen receptor therapy and personal experiences with treatment of patients with metastatic castration-sensitive prostate cancer. This is the second of 2 articles based on this event.

DISCUSSION QUESTIONS

  • What is your reaction to the updated results from the TITAN study (NCT02489318) of apalutamide (Erleada) plus androgen deprivation therapy (ADT)?
  • What about the final overall survival (OS) from the ARCHES study (NCT02677896) of enzalutamide plus ADT for metastatic castration-sensitive prostate cancer (mCSPC)? ​
  • What toxicities are most concerning to you in this setting? Which do you find most challenging to manage?​

ROBY THOMAS, MD: What’s your reaction to the updated results of the TITAN trial of apalutamide and ADT?

JOSE SILVA, MD: It’s a positive reaction, but I think the question we have, since there’s no direct comparison, is what apalutamide offers versus enzalutamide [Xtandi] as an indirect comparison.

THOMAS: For the final OS from the ARCHES study of enzalutamide and ADT for mCSPC, the OS data were more mature, since TITAN looked like it was a slight improvement relative to ARCHES.

But I think the big thing is, with ENZAMET [NCT02446405], they also allowed for docetaxel stratification, as well as with apalutamide in TITAN. It’s always hard to make cross-trial comparisons, and, when you look at ENZAMET, healthcare-related quality of life indices were fairly similar.1,2

How about your perspectives on the tolerability of apalutamide and ADT versus other ADT-based combination regimens?

KASRA KARAMLOU, MD: I think that tolerability of apalutamide and enzalutamide are very similar; I think they’re pretty similar drugs. A lot of it’s just personal experience.

THOMAS: Have any of you encountered the rash that comes with apalutamide when you first start?

VIVEK ABHYANKAR, MD: No, I have not.

THOMAS: It can happen, and it generally dissipates after the first 4 weeks. So, if you do run into that situation, it’s not necessarily something you’d have to halt therapy, or dose-reduce therapy for. But, I’m glad you haven’t run into that.

ELAINE BEED, MD: I think what the men complain about most are hot flashes, but we treat the breast cancer the same way, we put them on an antidepressant which usually helps.

THOMAS: Do you have a go-to antidepressant?

BEED: It just depends on what they’re on, or if they’re on anything. Usually, my nurse practitioner does all the…antidepressants, because she can’t do some of the chemotherapy.

THOMAS: Yoga seems to work for [hot flashes in] women in breast cancer, but it’s a challenging toxicity.

DISCUSSION QUESTIONS

  • What is your approach toward follow up and monitoring for a patient receiving apalutamide? ​
  • What clinical imaging or other findings trigger you to consider changing or adding therapy?​

THOMAS: Would any clinical imaging or other findings trigger you to consider changing or adding therapy? If you start seeing your patient’s PSA [prostate-specific antigen] level going up, what is your next step?

KARAMLOU: The simplest is making sure that they’re testosterone level is adequately suppressed. And, if that’s not the case, then they should likely go to a second-line therapy.

JED HENRY, MD: Do you do a testosterone check before you do any imaging? In urology, we rarely ever check testosterone to see if it’s suppressed. We usually just go straight to do a bone scan and a CT scan, see if there’s any metastases you can identify, etc. But we don’t do much testosterone evaluation to see if it’s suppressed or not.

THOMAS: It’s fairly rare to see that. In my case, I always need to prove that they’re castration-refractory by meeting the thresholds before enrolling them onto a clinical trial or getting authorization for the next medication.

Are there any symptoms you’d be concerned about? Are you switching therapy immediately, or looking to the next therapy? Are you going to follow, or trend, for a few PSA values, or wait until you get progression on imaging?

ABHYANKAR: I think sometimes there’s a role for volume of progression. Let’s say it is a solitary bone lesion, or it’s a single retroperitoneal node, that is where I ask, “Is this system-wide failure, or is it just a clone that is failing right now?”

ZACHARY HORNE, MD: The oligoprogression theory is that the patient has 1 clone, or a couple clones, that are escaping, but I prefer to continue on with all of the active therapeutic agents and radiate those sites of progression. It doesn’t work in everybody, but it works for some, and you can spare them the morbidity of the next line with minimal morbidity from radiation. It is worth a shot, even though it’s not always successful.

THOMAS: Are you using stereotactic body radiation therapy [SBRT], or standard external beam radiation?

HORNE: I will use whatever [my healthcare system] will let me do. If they’ve had previous radiation, it’s much easier to get SBRT approved, but that is not always the case. So, sometimes it’s more simple planning, and sometimes it’s more complicated. It depends on what I can convince the peer-to-peer reviewer of that day.

THOMAS: Are you seeing a PSA response out the gate?

HORNE: The last 2 patients who I treated for oligoprogression PSAs dropped back down to undetectable. They’re about 6 months out each, so for them it has been successful so far.

THOMAS: That’s great. [Also], if you have a patient who is symptomatic in any way, or something’s not adding up—weight loss or a lab abnormality—it’s always a consideration regardless of the PSA to get a scan for these patients to ensure that they’re not having some sort of small-cell differentiation.

DISCUSSION QUESTIONS

  • How do you ensure patients are able to complete therapy/remain adherent to oral therapy?​

THOMAS: Ensuring patients are able to complete therapy or remain adherent is a tough [challenge]. I have that problem in my clinic periodically with certain patients, and we don’t have a good software methodology to ensure that, other than if they’re on a clinical trial and they have to bring their bottles back.

BEED: They have to get it approved every time, every month, or 2 months, or 3 months, so if they don’t call in, we have the data there. If they don’t get it approved, we know they’re not taking it, because it has to keep going through the right channels, and my nurse complains about how often she has to fill those forms out. Usually, the patients are pretty honest.

THOMAS: Yes, I’ve had some problems.

MARIYA APOSTOLOVA, MD: We have some nurses who call them periodically to check for adverse events, so they monitor and ask if they’ve missed any doses. If they do, then we get a message on the electronic medical record.

References:

1. Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019;381(1):13-24. doi:10.1056/NEJMoa1903307

2. Stockler MR, Martin AJ, Davis ID, et al. Health-related quality of life in metastatic, hormone-sensitive prostate cancer: ENZAMET (ANZUP 1304), an international, randomized phase III trial led by ANZUP. J Clin Oncol. 2022;40(8):837-846. doi:10.1200/JCO.21.00941