First-Line Therapy Options for Metastatic Castration-Sensitive Prostate Cancer


An oncologist details the first-line therapy options for metastatic castration-sensitive prostate cancer.

Bobby Liaw, MD: The therapeutic landscape for first-line therapy for metastatic castration-sensitive prostate cancer has changed dramatically in recent years, as data for drugs such as docetaxel, abiraterone, apalutamide, and enzalutamide have been shown in their own individual randomized phase 3 studies to improve overall survival when used in people with metastatic castration-sensitive prostate cancer. A lot of the data started with the CHAARTED study, where it showed that the inclusion of 6 cycles of docetaxel in combination with ADT [androgen deprivation therapy] showed a significant improvement in overall survival for men with newly diagnosed de novo metastatic castration-sensitive prostate cancer.

With docetaxel, we need to consider disease volume while trying to figure out who would be a good candidate and who wouldn’t. That’s because as part of this study, we saw that patients with a high volume of disease are the ones who had the overall survival advantage with the addition of 6 cycles vs those who had low-volume disease didn’t seem to meet that mark. In regard to the definition of high-volume disease, the CHAARTED criteria considered the number of bone metastases—meaning 4 or more sites of bone disease, one being extra-axial—or the presence of visceral metastasis.

In looking at people who might not be a good candidate for chemotherapy, whether it’s anticipating difficulties tolerating it, or if we’re running into a patient preference where they don’t want to consider chemotherapy, we have 3 other drugs that fall within this androgen receptor pathway inhibitor that have also been very instrumental in showing overall survival advantage. Abiraterone, apalutamide, and enzalutamide all work in slightly different ways, although they all work on the androgen pathway axis.

Abiraterone showed its benefits in the LATITUDE study. In that particular study, they were looking at patients with high-risk disease, defined as a Gleason score of 8 or above, the presence of 3 or more sites of bone metastasis, or presence of visceral metastasis. Meanwhile, apalutamide and enzalutamide were both tested in a very broad selection of patients with metastatic prostate cancer, inclusive of both low-volume disease and high-volume disease. All 3 of these drugs—abiraterone, apalutamide, and enzalutamide—have met overall survival advantage in long-term follow-up and analysis.

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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