Table 1.
Efficacy of LHRH agonists and antagonists in combination with next-generation hormonal agents in prostate cancer*
| Author year; study phase (type of study) | Patient population | Race | Treatment duration | Regimen | N | Follow-up duration | Testosterone | PSA | Progression outcome |
|---|---|---|---|---|---|---|---|---|---|
| Neoadjuvant | |||||||||
| Cho 201591; phase 2 (single arm) | Intermediate-risk disease (GS of 7, or PSA 10–20) or high-risk disease (T3/4, GS 8–10 or PSA > 20) | NR | 24 weeks (12 weeks of neoadjuvant followed by concurrent phase with radiation therapy) | Goserelin or leuprolide + abiraterone + RT | 22 | 21 months | Testosterone decline: 99.9% | Median pre-radiation PSA at 12 weeks: 0.05 ng/mL. All 21 men who complied with at least 3 months of abiraterone had a pre-radiation PSA nadir: ≤ 0.3 ng/mL. Post radiation PSA undetectable in 19/22 patients and: all patients who completed the neoadjuvant and concurrent portions of the study (n = 16). |
21/22 patients had not experienced biochemical relapse |
| Shee 202292; phase 2 (single arm) | High-risk localized or regional PC, having ≥ 2 of the following criteria: cT3a/b, PSA ≥ 20 ng/mL, GS 8–10, ≥ 33% core involvement on prostate biopsy; or ≥ 1 cm pelvic lymph node(s) | White: 54.5%; Black: 18.2%; Asian: 9.1%; unknown: 18.2% | 24 months before RT | Leuprolide + enzalutamide | 11 | 35.5 months | Median time to testosterone < 50 ng/dL from initiation of ADT: 1.73 months; median nadir testosterone: 18 ng/dL | Achieved PSA-CR (PSA nadir ≤ 0.3 ng/mL) at 120 days of ADT: 90.9%. Median time to PSA-CR was: 4.20 months, and median nadir PSA was: 0.015 ng/mL. |
Biochemical recurrence: 0% at 24 months and 11% at 36 months |
| Bastos 202293; phase 2 (randomized trial) | High-risk localized PC, GS ≥ 8 and/or cT3N0-1 and/or PSA ≥ 20 ng/mL | NR | 3 months neoadjuvant before RP | Goserelin + abiraterone + RP | 31 | 2.6 years | Testosterone recovery: 84% | NR | Biochemical relapse: 32% pCR or MRD: 7%; complete PSMA response: 23%. |
| Karzai 201994; phase 2 (single arm) | Newly diagnosed, high-risk PC | NR | 6 months neoadjuvant before RP | Goserelin + enzalutamide + RP | 33 | NR | NR | Median on-study PSA was: 9.58 ng/dL. Median PSA after 6 months of goserelin + enzalutamide was: < 0.02 (0.02–0.35 ng/mL). |
NR |
| Efstathiou 201995; phase 2 (randomized trial) | PC without metastasis, ≥ T1c with GS 8–10 or ≥ T2b with GS of 7 and PSA ng/mL | NR | 3 months before RP | Leuprolide + abiraterone + RP | 44 | ≥ 4 years | NR | PSA ≤ 0.1 ng/mL: 84% | 3-year relapse-free survival: 75%; biochemical recurrence: 44% |
| Leuprolide + RP | 21 | ≥ 4 years | NR | PSA ≤ 0.1 ng/mL: 5% | 3-year relapse-free survival: 71%; biochemical recurrence: 59% | ||||
| McKay 201996; phase 2 (randomized trial) | GS ≥ 7 or ≥ 1 cm tumor on MRI, PSA > 20 ng/mL, or T3 | White: 90%; Black or African American: 6%; other: 4% | 24 weeks neoadjuvant before RP | Leuprolide + enzalutamide + abiraterone + RP | 50 | NR | NR | PSA ≤ 0.2 ng/mL (% patients): 96% (before RP) | pCR or MRD at RT: 30% |
| White: 80%; Black or African American: 12%; Asian: 8% | Leuprolide + enzalutamide + RP | 25 | NR | NR | PSA ≤ 0.2 ng/mL (% patients): 100% (before RP) | pCR or MRD at RT: 16% | |||
| Taplin 201497; phase 2 (randomized trial) | Localized PC and 1 of the following: PSA > 10 ng/mL, PSA velocity > 2 ng/mL per year (in preceding 12 months), and GS ≥ 7 | NR | 24 weeks neoadjuvant before RP | Leuprolide (24 w) + RP | 28 | 24 weeks | Testosterone (mean): baseline 429.4 → 12 w: 17.3 → 24 w: 5.3 ng/dL | 24 w PSA (median): 0.06 ng/dL 24 w PSA ≤ 0.2 ng/mL: 82% |
pCR or MRD: 48% |
| NR | Leuprolide (24 w) + abiraterone (24 w) + RP | 30 | 24 weeks | Testosterone (mean): baseline 425.1 → 12 w: 6.7 → 24 w: 15.5 ng/dL | 24 w PSA (median): 0.04 ng/dL 24 w PSA ≤ 0.2 ng/mL: 93% |
pCR or MRD: 62% | |||
| Salvage | |||||||||
| Freedland 202398; phase 3 (randomized trial) | High-risk (PSA doubling time of ≤ 9 months and a PSA level of ≥ 2 ng/mL above nadir after radiation therapy or ≥ 1 ng/mL after radical prostatectomy with or without postoperative radiation therapy, testosterone ≥ 150 ng/dL, and an ECOG PS 0 or 1 | White: 82.5%; Asian: 7.3%; Black: 4.5; other: 2.8%; not reported: 2.8% | 36 weeks if the PSA at week 36 was < 0.2 ng/mL and restarted with increased PSA | Leuprolide + enzalutamide | 355 | 60.7 months | NR | Free from PSA progression at 5 years: 97.4%; 90.9% of patients had treatment suspended for a median of 20.2 months. | 5-year metastasis-free survival: 87.3% |
| White: 83.1%; Asian: 7.3%; Black: 4.2; other: 1.4%; not reported: 3.9% | Enzalutamide | 355 | 60.7 months | NR | Free from PSA progression at 5 years: 88.9%; 85.9% of patients had treatment suspended for a median of 11.1 months | 5-year metastasis-free survival: 80.0% | |||
| White: 84.1%; Asian: 7.3%; Black: 4.5; other: 2.5%; not reported: 1.4% | Leuprolide | 358 | 60.7 months | NR | Free from PSA progression at 5 years:70.0%; 67.8% of patients had treatment suspended for a median of 16.8 months. | 5-year metastasis-free survival: 71.4% | |||
| Autio 202199; phase 2 (randomized trial) | Had undergone an RP for localized PC; experienced biochemical recurrence; PSA doubling time at the time of trial entry: ≤ 9 months; testosterone level ≤ 150 ng/dL | White: 80%; Black or African American: 15%; unknown: 5% | 8 months | Degarelix + abiraterone | 41 | 18 months | Median time to testosterone recovery (from treatment start): 56 weeks; undetectable PSA with testosterone recovery at 18 months: 17.1% | Undetectable PSA level at 8 months: 87.8% | PSA progression: 64.4 weeks |
| White: 93%; Black or African American: 7% | Degarelix | 42 | Median time to testosterone recovery: 52.9 weeks; undetectable PSA with testosterone recovery at 18 months: 11.9% | Undetectable PSA level at 8 months: 66.7% | PSA progression: 54.9 weeks | ||||
| White: 90%; Black or African American: 10% | Abiraterone | 39 | Median time to testosterone recovery: 36 weeks; undetectable PSA with testosterone recovery at 18 months: 5.1% | Undetectable PSA level at 8 months: 83.8% | PSA progression: 37.5 weeks | ||||
| Advanced | |||||||||
| Maluf 2021100; phase 2 (randomized trial) | (1) Locally advanced PC with positive lymph nodes, not candidates for radical surgery or RT and PSA ≥ 2 ng/mL; (2) high-risk biochemical recurrence: PSA ≥ 4 ng/mL and PSA doubling time < 10 months, or PSA ≥ 20 ng/mL; or (3) metastatic CSPC and PSA ≥ 2 ng/mL | NR | 25 weeks (study treatment continued only at investigator discretion) | Goserelin + abiraterone | 42 | 14 months | Testosterone level < 50 ng/dL (castration level) at week 25: 97.5% | PSA ≤ 0.2 ng/mL (% patients): 75.6% (at week 25); PSA decline ≥ 50%: 100%; PSA decline ≥ 80%: 100% | Radiographic progression (at week 25): 3.1% |
| George 2023101; phase 3 (randomized trial) | Advanced PC eligible for at least 1 year of continuous ADT | NR | 48 weeks | Leuprolide + enzalutamide | 9 | NR | Sustained testosterone suppression below castration levels (< 50 ng/dL) from day 29 through 48 weeks: 90.9% (concomitant enzalutamide or docetaxel) | NR | NR |
| NR | Relugolix + enzalutamide | 20 | NR | Sustained testosterone suppression below castration levels (< 50 ng/dL) from day 29 through 48 weeks: 95.8% (concomitant enzalutamide or docetaxel); testosterone (median): 12.71 ng/dL | NR | NR | |||
ADT, androgen deprivation therapy; CSPC, castration-sensitive prostate cancer; GS, Gleason score; MRD, minimal residual disease; MRI, magnetic resonance imaging; NR, not reported; PC, prostate cancer; pCR, pathologic complete response; PSA, prostate-specific antigen; PSA-CR, PSA complete response; PSMA, prostate specific membrane antigen; RP, radical prostatectomy; RT, radiotherapy; w, weeks.
*A literature search was performed in core databases and supplemented by searching for studies published before February 2024.