The development of drugs like abiraterone acetate and enzalutamide has stimulated new research into the use of such agents early on, in combination with first-line therapy, to see if it can affect the outcomes for men with high-risk and unfavorable intermediate-risk prostate cancer.
In a recent paper by Montgomery et al., clinical researchers have reported data from a study in which 52 patients with either intermediate- or high-risk forms of prostate cancer were assigned to receive one or other of two types of neoadjuvant therapy prior to treatment by radical prostatectomy:
- The 25 evaluable patients in Group A were treated with neoadjuvant enzalutamide alone for 6 months prior to surgery.
- The 23 evaluable patients in Group B were treated with neoadjuvant enzalutamide + an LHRH agonist + dutasteride for 6 months prior to surgery.
The objective was to see whether such treatments had significant but differing impact on a variety of measurable outcomes at time of surgery, including:
- The complete absence of any cancer in the prostate on post-surgical pathology, referred to as a pathologic complete response or pCR (compared to historical control data of 5 percent based on older studies in which neoadjuvant flutamide + an LHRH agonist had been given prior to surgery)
- “Minimal residual disease” in the prostate (MRD), which meant residual cancer in the prostate with a diameter of ≤ 3 mm
- “Residual cancer burden” in the prostate (RCD), i.e., the total volume of cancer found in the prostate post-surgery
- PSA level
- Concentrations of androgens like dihydrotestosterone in the prostate tissue and in the patients’ bloodstream
Here are the basic study findings:
- Among the patients in Group A
- 0/25 patients achieved either a pCR or MRD.
- Average (median) RCB = 0.41 cm3
- Among the patients in Group B
- 1/23 patients (4.3 percent) achieved a pCR.
- 3/23 patients (13.0 percent) achieved MRD.
- Average (median) RCB = 0.06 cm3
- Prostate tissue levels of testosterone and dihydrotestosterone correlated with the levels of RCB.
- There were no drug discontinuations as a consequence of adverse events to the drugs used in the study.
Montgomery et al. conclude that the combination of enzalutamide + dutasteride + an LHRH agonist produced rates of pCR and MRD that were comparable to historical controls with flutamide + an LHRH agonist.
The implication is that this type of aggressive neoadjuvant therapy prior to surgery is unable to eliminate risk for disease progression in men with intermediate- and high-risk forms of prostate cancer, which was also found to be the case years ago when this was tried with the combination of an antiandrogen (flutamide) and an LRHR agonist.