Metastatic Castration-Sensitive Prostate Cancer: Comparing First-Line Therapy Options


Dr. Bobby Liaw compares the available first-line therapy options for metastatic castration-sensitive prostate cancer and explains how to decide on a therapy.

Bobby Liaw, MD: All 4 of these drugs are excellent options for someone who’s coming in with a new diagnosis of metastatic castration-sensitive prostate cancer. Unfortunately, none of the studies compared one drug to another. They were all compared to placebo, which is reasonable because that was the standard of care at the time that all these studies were designed. But that puts us in a difficult position. You have a lot of different drugs that all have excellent data to support their use, with docetaxel being the one that’s a little different in that it’s chemotherapy, where we know that volume of disease matters. That tends to be the main reason we may or may not choose chemotherapy.

Although in my own personal practice, for people with very symptomatic disease, when you want to try to effectively improve upon symptomatology as quickly as possible, I find that docetaxel may be a good solution in that type of a situation. Of course, we need to consider some individual characteristics of the patients being selected for treatment. For people who are much older, for whom we might anticipate difficulty in tolerance with chemotherapy, we may want to select one of the oral agents instead.

As far as abiraterone vs apalutamide vs enzalutamide, it becomes a little more difficult to choose sometimes. Abiraterone requires the concurrent use of a steroid on a daily basis to combat some of its adverse effects. Additionally, for abiraterone, we need to consider that there needs to be some regular maintenance laboratory tests performed in order to make sure there aren’t going to be any issues with LFT [liver function test] derangements as well as electrolyte derangements, because these are adverse effects of the medications that need to be monitored closely.

Drugs like apalutamide and enzalutamide don’t require as many of these maintenance laboratory tests. For patients who are perhaps a little less willing to come for frequent laboratory checks, these may be better drugs to select in those situations. I tend to favor abiraterone whenever I choose one of these, but for the right patients, for people who I know will run into difficulties with the steroid use, such as if they have diabetes or they already have pretty brittle bones, if we already have issues with metabolic disorders where I want to avoid the steroid use, I often will choose either apalutamide or enzalutamide.

One additional thought that needs to be considered going forward is whether we should be thinking about triplet therapy. Recently presented at ESMO [European Society for Medical Oncology Congress] in 2021 were some of the early findings from the PEACE-1 study, where there was an experience in using ADT [androgen deprivation therapy] plus docetaxel plus abiraterone. What we’re seeing in early analysis is that using the 3-drug combination up front actually led to better outcomes than in men who use just 2 drugs in de novo metastatic hormone-sensitive prostate cancer. A lot of the early data show that when abiraterone was added to ADT and docetaxel, there was a significant improvement in overall survival, with a hazard ratio of 0.75, meaning that men experience an additional 25% reduction in risk of death compared with ADT and docetaxel alone.

There needs to be some additional follow-up on these study data before we get a better sense of how tumor burden, volume of disease, affects survival in these 2 different groups. But so far, it seems that the triplet regimen is significant in providing additional years of disease control without progression in men with high-burden disease. It’s more about whether we’ll see the same benefit bear out on patients with low-burden disease. It’s a significant consideration. At this moment, when it comes to people with high-risk disease, someone for whom you’re hoping to be able to optimally control the disease immediately and better control their disease in the long term, especially patients who are younger who can tolerate some of the additional mild adverse effects that come with the addition of abiraterone to docetaxel, the triplet regimen is something that is increasingly crossing my mind to offer to some of my patients.

Transcript edited for clarity.

Case: A 73-Year-Old Man With Biochemical Recurrence of Prostate Cancer and Metastatic Castration-sensitive High-volume Disease

January 2018

Initial Presentation

A 73-year-old man presents with urinary retention, fatigue and decreased appetite

Patient History, Lifestyle and Clinical workup

History of mild alcoholic liver cirrhosis

No family history of prostate cancer

Patient is active and is very involved in his grandchildren’s activities

TRUS and biopsy revealed adenocarcinoma of the prostate gland, Gleason score 8 [4+4] with disease in 10/12 cores.

PSA 150 ng/mL; Hb 9.7 g/dL; ANC 1.9

Liver function tests are abnormal

Initial Diagnosis and Treatment

Patient is diagnosed with localized prostate cancer

He undergoes robotic radical prostatectomy with subsequent PSA decrease (12 ng/mL)

CT and bone scans showed no residual disease

October 2019

Presentation at Recurrence

Patient complains of right hip pain and abdominal pain

Imaging with CT and bone scan showed multiple metastatic bone lesions in the pelvis and diffuse liver lesions

PSA 90 ng/mL; Hb 9.4 g/dL; ANC 1.5

Liver function tests continue to be abnormal

Diagnosis of Recurrence

Patient is diagnosed with biochemical recurrence of prostate cancer with high-volume castration-sensitive metastatic disease

Germline genetic testing is negative

Treatment for Recurrence

Patient wishes to receive oral treatment with good quality of life so he can continue to be involved in his grandchildren’s activities

Due to his abnormal liver function tests and desire to receive oral treatment, he is started on ADT + apalutamide

At his 1-year follow-up, the patient’s PSA remains undetectable

Follow-up imaging shows stable disease, and he continues to report a good quality of life

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