Dataset Information

Coadministration of Apalutamide and Relugolix in Patients with Localized Prostate Cancer at High Risk for Metastases.

ABSTRACT:

Background

The single-arm, open-label, multicenter, phase II Apa-RP study evaluates the biochemical recurrence (confirmed prostate-specific antigen [PSA] > 0.2 ng/mL)-free rate in patients with high-risk localized prostate cancer (HR-LPC) after radical prostatectomy following adjuvant apalutamide and androgen-deprivation therapy. In this substudy, relugolix, an oral gonadotropin-releasing hormone antagonist, was evaluated in combination with apalutamide.

Objective

The aim of this study was to evaluate whether the approved standard maintenance dose of relugolix in combination with apalutamide sustains castrate testosterone levels (< 50 ng/dL).

Patients and methods

Twelve patients with HR-LPC who met all the main study criteria were included in the substudy. Patients received relugolix monotherapy for 2 weeks (loading dose [360 mg] at Day - 14 then 120 mg/day daily until Day - 1), then daily relugolix (120 mg) with apalutamide (240 mg) from Day 1 to Day 28. Endpoints were rate of maintained castration (testosterone < 50 ng/dL) through Day 28 (primary) and safety (secondary).

Results

All 12 patients received relugolix and apalutamide and achieved castrate testosterone levels after 2-week relugolix monotherapy (median testosterone 348.5 ng/dL and 8.7 ng/dL at Days - 14 and - 1). All 11 patients who had testosterone measured at Day 28 maintained castrate testosterone (median 10.0 ng/dL) without relugolix dose adjustment. Treatment-emergent adverse events (TEAEs) occurred in nine patients during relugolix monotherapy and in eight patients during relugolix + apalutamide coadministration. Hot flush was the most common TEAE reported, in six and four patients, respectively.

Conclusions

Relugolix administered at approved standard doses concurrently with apalutamide was effective in maintaining castrate testosterone levels in HR-LPC without new safety signals.

Trial registration number and date

NCT04523207, 21 August 2020.

SUBMITTER: Brown G

PROVIDER: S-EPMC9928932 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Coadministration of Apalutamide and Relugolix in Patients with Localized Prostate Cancer at High Risk for Metastases.

Brown Gordon G Belkoff Laurence L Hafron Jason M JM Saltzstein Daniel R DR Potdar Rushikesh R Bhaumik Amitabha A Phillips Jennifer J McGowan Tracy T Shore Neal D ND

Targeted oncology 20221206 1

<h4>Background</h4>The single-arm, open-label, multicenter, phase II Apa-RP study evaluates the biochemical recurrence (confirmed prostate-specific antigen [PSA] > 0.2 ng/mL)-free rate in patients with high-risk localized prostate cancer (HR-LPC) after radical prostatectomy following adjuvant apalutamide and androgen-deprivation therapy. In this substudy, relugolix, an oral gonadotropin-releasing hormone antagonist, was evaluated in combination with apalutamide.<h4>Objective</h4>The aim of this ...[more]

PMID: 36472728

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Project description:PurposeExisting definitions of high-risk prostate cancer consist of men who experience significant heterogeneity in outcomes. As such, criteria that identify a subpopulation of National Comprehensive Cancer Network (NCCN) high-risk prostate cancer patients who are at very high risk (VHR) for poor survival outcomes following prostatectomy were recently developed at our institution and include the presence of any of the following disease characteristics: multiple NCCN high-risk factors, primary Gleason pattern 5 disease and/or ≥5 biopsy cores with Gleason sums of 8 to 10. Whether these criteria also apply to men undergoing definitive radiation is unclear, as is the optimal treatment regimen in these patients.Methods and materialsAll men consecutively treated with definitive radiation by a single provider from 1993 to 2006 and who fulfilled criteria for NCCN high-risk disease were identified (n=288), including 99 patients (34%) with VHR disease. Multivariate-adjusted competing risk regression models were constructed to assess associations between the VHR definition and biochemical failure (BF), distant metastasis (DM), and prostate cancer-specific mortality (PCSM). Multivariate-adjusted Cox regression analysis assessed the association of the VHR definition with overall mortality (OM). Cumulative incidences of failure endpoints were compared between VHR men and other NCCN high-risk men.ResultsMen with VHR disease compared to other NCCN high-risk men experienced a higher 10-year incidence of BF (54.0% vs 35.4%, respectively, P<.001), DM (34.9% vs 13.4%, respectively, P<.001), PCSM (18.5% vs 5.9%, respectively, P<.001), and OM (36.4% vs 27.0%, respectively, P=.04). VHR men with a detectable prostate-specific antigen (PSA) concentration at the end of radiation (EOR) remained at high risk of 10-year PCSM compared to VHR men with an undetectable EOR PSA (31.0% vs 13.7%, respectively, P=.05).ConclusionsNCCN high-risk prostate cancer patients who meet VHR criteria experience distinctly worse outcomes following definitive radiation and long-term androgen deprivation therapy, particularly if an EOR PSA is detectable. Optimal use of local therapies for VHR patients should be explored further, as should novel agents.

Project description:ImportanceThere is a lack of data evaluating the association of surgical delay time (SDT) with outcomes in patients with localized, high-risk prostate cancer.ObjectiveTo investigate the association of SDT of radical prostatectomy and final pathological and survival outcomes.Design, setting, and participantsThis cohort study used data from the US National Cancer Database (NCDB) and identified all patients with clinically localized (cT1-2cN0cM0) high-risk prostate adenocarcinoma diagnosed between 2006 and 2016 who underwent radical prostatectomy. Data analyses were performed from April 1 to April 12, 2020.ExposuresSDT was defined as the number of days between the initial cancer diagnosis and radical prostatectomy. SDT was categorized into 5 groups: 31 to 60, 61 to 90, 91 to 120, 121 to 150, and 151 to 180 days.Main outcomes and measuresThe primary outcomes were predetermined as adverse pathological outcomes after radical prostatectomy, including pT3-T4 disease, pN-positive disease, and positive surgical margin. The adverse pathological score (APS) was defined as an accumulated score of the 3 outcomes (0-3). An APS of 2 or higher was considered a separate outcome to capture cases with more aggressive pathological features. The secondary outcome was overall survival.ResultsOf the 32 184 patients included in the study, the median (interquartile range) age was 64 (59-68) years, and 25 548 (79.4%) were non-Hispanic White. Compared with an SDT of 31 to 60 days, longer SDTs were not associated with higher risks of having any adverse pathological outcomes (odds ratio [OR], 0.95; 95% CI, 0.80-1.12; P = .53), pT3-T4 disease (OR, 0.99; 95% CI, 0.83-1.17; P = .87), pN-positive disease (OR, 0.79; 95% CI, 0.59-1.06; P = .12), positive surgical margin (OR, 0.88; 95% CI, 0.74-1.05; P = .17), or APS greater than or equal to 2 (OR, 0.90; 95% CI, 0.74-1.05; P = .17). Longer SDT was also not associated with worse overall survival (for SDT of 151-180 days, hazard ratio, 1.12; 95% CI, 0.79-1.59, P = .53). Subgroup analyses performed for patients with very high-risk disease (primary Gleason score 5) and sensitivity analyses with SDT considered as a continuous variable yielded similar results.Conclusions and relevanceIn this cohort study of patients who underwent radical prostatectomy within 180 days of diagnosis for high-risk prostate cancer, radical prostatectomy for high-risk prostate cancer could be safely delayed up to 6 months after diagnosis.

Dataset Information

Coadministration of Apalutamide and Relugolix in Patients with Localized Prostate Cancer at High Risk for Metastases.

Background

Objective

Patients and methods

Results

Conclusions

Trial registration number and date

Publications

Coadministration of Apalutamide and Relugolix in Patients with Localized Prostate Cancer at High Risk for Metastases.

Similar Datasets

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