A prospective trial of abiraterone acetate plus prednisone in Black and White men with metastatic castrate-resistant prostate cancer.

BACKGROUND: Retrospective analyses of randomized trials suggest that Black men with metastatic castration-resistant prostate cancer (mCRPC) have longer survival than White men. The authors conducted a prospective study of abiraterone acetate plus prednisone to explore outcomes by race. METHODS: This race-stratified, multicenter study estimated radiographic progression-free survival (rPFS) in Black and White men with mCRPC. Secondary end points included prostate-specific antigen (PSA) kinetics, overall survival (OS), and safety. Exploratory analysis included genome-wide genotyping to identify single nucleotide polymorphisms associated with progression in a model incorporating genetic ancestry. One hundred patients self-identified as White (n = 50) or Black (n = 50) were enrolled. Eligibility criteria were modified to facilitate the enrollment of individual Black patients. RESULTS: The median rPFS for Black and White patients was 16.6 and 16.8 months, respectively; their times to PSA progression (TTP) were 16.6 and 11.5 months, respectively; and their OS was 35.9 and 35.7 months, respectively. Estimated rates of PSA decline by ≥50% in Black and White patients were 74% and 66%, respectively; and PSA declines to <0.2 ng/mL were 26% and 10%, respectively. Rates of grade 3 and 4 hypertension, hypokalemia, and hyperglycemia were higher in Black men. CONCLUSIONS: Multicenter prospective studies by race are feasible in men with mCRPC but require less restrictive eligibility. Despite higher comorbidity rates, Black patients demonstrated rPFS and OS similar to those of White patients and trended toward greater TTP and PSA declines, consistent with retrospective reports. Importantly, Black men may have higher side-effect rates than White men. This exploratory genome-wide analysis of TTP identified a possible candidate marker of ancestry-dependent treatment outcomes.

Intensifying Salvage Therapy in Prostate-specific Antigen Recurrent Prostate Cancer After Radical Prostatectomy with Apalutamide, Salvage Radiation, and Docetaxel: The Phase 2 STARTAR Trial.

BACKGROUND AND OBJECTIVE: Androgen deprivation therapy (ADT) with salvage radiation therapy (RT) improves survival for patients with prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP) for prostate cancer (PC), but many patients suffer further relapse. This study aims to determine the benefit of the combination of ADT, apalutamide, salvage RT, and docetaxel for high-risk PSA recurrent PC. METHODS: STARTAR is a multicenter, investigator-initiated phase 2 trial of men with PSA recurrent PC after RP. The key inclusion criteria included M0 by computed tomography/bone scan, Gleason 7 with either T3/positive margin/N1 disease or Gleason 8-10 prostate adenocarcinoma, PSA relapse (0.2-4 ng/ml) <4 yr after RP, and fewer than four positive resected lymph nodes. Patients received ADT with apalutamide for 9 mo, RT starting week 8, and then six cycles of docetaxel. The primary endpoint was 36-mo progression-free survival (PFS) with testosterone recovery and compared against the prior STREAM trial. KEY FINDINGS AND LIMITATIONS: We enrolled 39 men, including those with Gleason 8-10 (46%), pN1 (23%); the median PSA was 0.58 ng/ml. The median follow-up was 37 mo. All patients achieved undetectable PSA nadir. At 24 and 36 mo, PFS rates were 84% and 71%, respectively, which improved significantly over 3-yr 47% historic PFS and 54% enzalutamide/ADT/RT (STREAM) PFS rates (p = 0.004 and p = 0.039, respectively). Common any-grade adverse events included 98% hot flashes, 88% fatigue, 77% alopecia, 53% rash (10% G3), and 5% febrile neutropenia. CONCLUSIONS AND CLINICAL IMPLICATIONS: In this phase 2 trial of ADT, apalutamide, salvage RT, and six cycles of docetaxel for high-risk PSA recurrence, the 3-yr PFS rate improved to 71%, indicating feasible and efficacious treatment intensification, with durable remissions beyond historic data. PATIENT SUMMARY: Prostate cancer recurrence after surgical removal of the tumor occurs often, and current treatment options to limit recurrence after surgery are only partially effective. In this study, we found that the addition of an androgen receptor inhibitor and docetaxel chemotherapy to standard postsurgery radiation therapy and androgen deprivation therapy significantly improved progression-free survival at 3 yr after treatment. These results suggest that intensification of treatment after surgery can provide long-term benefit to a subset of patients with high-risk prostate cancer.

Phase II Trial of Enzalutamide and Androgen Deprivation Therapy with Salvage Radiation in Men with High-risk Prostate-specific Antigen Recurrent Prostate Cancer: The STREAM Trial.

BACKGROUND: Salvage external beam radiotherapy (RT) with androgen deprivation therapy (ADT) improves survival over RT in men with prostate cancer (PC) and rising prostate-specific antigen (PSA) levels after radical prostatectomy (RP). OBJECTIVE: To investigate the safety and efficacy of enzalutamide concurrent with salvage RT and ADT. DESIGN, SETTING, AND PARTICIPANTS: This was a three-center prospective phase 2 single-arm trial (NCT02057939) of men with Gleason 7-10 PC and PSA recurrence within 4 yr of RP ranging from 0.2 to 4.0 ng/dl, no prior hormonal therapy, and no radiographic evidence of metastases. We enrolled 38 men; 37 completed therapy and were evaluable with testosterone recovery at 2 yr. INTERVENTION: Six months of ADT with 160 mg/d enzalutamide and 66 Gy RT to the prostate bed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was improved 2-yr progression-free survival (PFS) over historical controls. Secondary objectives included 3-yr PFS, safety, and patient-reported quality of life (QOL). RESULTS AND LIMITATIONS: The primary endpoint of 2-yr PFS was 65% (95% confidence interval [CI]: 47, 78) versus 51% (95% CI: 33, 67) in a trial of men with similar eligibility treated with salvage RT and adjuvant docetaxel. The 3-yr PFS was 53%. Eleven (29%) men experienced G3 toxicities, and there were no G4-5 or unexpected toxicities. QOL data suggest modest worsening of bowel, bladder, and hormonal symptoms at 3 mo, with recovery by 24 mo in most men. CONCLUSIONS: Salvage RT with enzalutamide and ADT following RP for men with PSA recurrent high-risk PC is safe and demonstrates encouraging efficacy, warranting prospective controlled phase 3 trials of ADT with or without potent androgen receptor inhibition in this curative-intent setting. PATIENT SUMMARY: Addition of 6 mo of oral daily enzalutamide to standard salvage radiation and hormone therapy is safe and may improve prostate cancer remission rates at 2 and 3 yr.