Intense neoadjuvant ADT explored in locally advanced prostate cancer
medwireNews: Intense androgen deprivation therapy (ADT) before radical prostatectomy (RP) benefits some patients with locally advanced prostate cancer, report researchers who found that results may be better with a four-drug than a two-drug regimen.
The phase II trial included 75 patients who were randomly assigned to receive neoadjuvant treatment with an ELAP regimen (abiraterone 1000 mg/day, enzalutamide 160 mg/day, leuprolide 22.5 mg every 12 weeks, and prednisone 5 mg/day) or an EL regimen (enzalutamide and leuprolide only). Both regimens were given for 24 weeks (six cycles) prior to RP.
All patients had a Gleason score of 7 or greater, a prostate-specific antigen (PSA) level higher than 20 ng/mL, or stage T3 disease by prostate magnetic resonance imaging. The majority (87%) had high-risk disease by National Comprehensive Cancer Network criteria.
At the time of surgery, the pathologic complete response (pCR) rate was 10% in the ELAP group and 8% in the EL group, while the rates of minimal residual disease (residual tumor ≤5 mm) were 20% and 8%, respectively.
Taken together, numerically more ELAP-treated patients achieved the primary outcome of pCR or minimal residual disease than did EL-treated patients (30 vs 16%), but the difference was not statistically significant.
Mary-Ellen Taplin (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and co-workers say that “[d]espite robust targeting of the androgen axis, the pCR rate has not increased” compared with previous studies in which they investigated the efficacy of abiraterone or enzalutamide separately.
They suggest this may be due to “a decreased effect size and, therefore, an insufficient sample size to detect differences; a need for more-prolonged ADT; inherent resistance mechanisms; and a lack of a biomarker to target tumors most likely to benefit.”
There was also no significant difference between the two arms in median presurgery PSA nadir, and the rates of ypT3 disease, positive margins, or positive lymph nodes.
The investigators note that “treatment was well-tolerated,” and treatment-related adverse events rates were generally comparable between the arms.
The team also found that both tumor ERG positivity and PTEN loss were associated with larger residual tumors at RP, with the largest residual tumor volume seen among tumors harbouring both alterations.
Taplin et al say that this observation “may be the consequence of either larger baseline tumor volumes, tumor heterogeneity, and/or low AR [androgen receptor] dependency, which suggests resistance to intense ADT.”
They continue: “This is supported by our findings that ERG-positive and PTEN-loss tumors were associated with lower AR expression, a trend toward a lower baseline PSA, and higher tumor volume in baseline biopsy specimens.”
Writing in the Journal of Clinical Oncology, Taplin and team conclude: “Although efficacy is not proven, neoadjuvant therapy combined with RP holds promise for men with poor-prognosis prostate cancer.”
They add: “Our hypothesis will be tested in a phase III trial of intense ADT and RP for men with locally advanced prostate cancer.”
By Laura Cowen
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