Combined abiraterone acetate plus prednisone, salvage prostate bed radiotherapy and LH-RH agonists (CARLHA-GEP12) in biochemically-relapsing prostate cancer patients following prostatectomy: A phase I study of the GETUG/GEP

Supiot, S.; Campion, Loı̈c; Pommier, P.; Doré, M.; Palpacuer, Clément; Racadot, S.; Rio, E.; Milano, Gérard; Oukhatar, Céline Mahier Ait; Carrié, C.

doi:10.18632/oncotarget.25189

Cited by 13 publications

(9 citation statements)

References 29 publications

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“…Thus, a further intensification of therapy may be warranted for patients with PET-positive lymph nodes or distant metastases. This might possibly be resolved by either the administration of higher radiation doses to PET-positive regions [ 39 ], an enlargement of radiation volumes [ 40 ], or by adding more aggressive systemic therapy regimens like concomitant docetaxel or abiraterone to sRT [ 41 , 42 ]. However, it is worth mentioning that patients with no metastases on PET and favorable accompanying risk factors had high two- and three-year BRFS rates of >74% and >66%, respectively.…”

Section: Discussionmentioning

confidence: 99%

Outcome After 68Ga-PSMA-11 versus Choline PET-Based Salvage Radiotherapy in Patients with Biochemical Recurrence of Prostate Cancer: A Matched-Pair Analysis

Hegemann

Rogowski

Eze

et al. 2020

Cancers

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The purpose of this analysis was primarily to analyze biochemical-recurrence free survival (BRFS) after positron emission tomography (PET)-guided salvage radiotherapy (sRT) in a large cohort, and to further compare BRFS after PSMA vs. choline PET/ computer tomography (CT)-based sRT. This retrospective analysis is based on 421 patients referred for PSMA or choline PET/CT after radical prostatectomy due to biochemically recurrent or persistent disease. BRFS (PSA: 0.2 ng/mL) was defined as the study endpoint. Cox regression analyses were performed to assess the impact of different clinical parameters on BRFS. Additionally, propensity score matching was performed to adjust patient cohorts (PSMA vs. choline PET/CT-based sRT). The median follow-up time was 30 months. BRFS at three years after sRT was 58%. In the multivariate analysis, only PSA before PET imaging and PSA before sRT were significantly associated with BRFS (p < 0.05). After propensity score matching, 272 patients were further analyzed; there was no significant difference in three-year BRFS between patients with PSMA PET-based vs. choline PET-based sRT (55% vs. 63%, p = 0.197). The present analysis confirmed the overall high BRFS rates after PET-based sRT and the strong prognostic effect of PSA level prior to sRT. PSMA PET-based sRT did not have superior BRFS rates when compared with choline PET-based sRT.

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Section: Discussionmentioning

confidence: 99%

Outcome After 68Ga-PSMA-11 versus Choline PET-Based Salvage Radiotherapy in Patients with Biochemical Recurrence of Prostate Cancer: A Matched-Pair Analysis

Hegemann

Rogowski

Eze

et al. 2020

Cancers

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“…Three trials of abiraterone combined with rt were found (Table iv). A single phase i study investigated the safety of combining abiraterone with salvage rt 54 and two phase ii trials evaluated efficacy based on the extent of castration as assessed by testosterone level 52,53 . The two phase ii trials varied in their populations and adt durations.…”

Section: Clinical Trials Combining Abiraterone Acetate With Rtmentioning

confidence: 99%

Combining Prostate Cancer Radiotherapy with Therapies Targeting the Androgen Receptor Axis

et al. 2019

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Background Prostate cancer (pca) is the most common non-dermatologic cancer and the 3rd leading cause of male cancer mortality in Canada. In patients with high-risk localized or recurrent pca, management typically includes the combination of long-term androgen deprivation therapy (adt) and radiotherapy (rt). New androgen-receptor-axis targeted therapies (arats), which await validation, offer an option to intensify therapy.Methods In this narrative review, we report the relevant history that has supported combining adt with rt. The literature in PubMed was searched for studies involving pca and novel arats (abiraterone acetate, enzalutamide, apalutamide, darolutamide) published between 1995 and 2019. Literature discussing clinical trials in which those modalities were combined was extracted and synthesized into a combined molecular and clinical discussion. Potential treatment intensification mechanisms and rationales are explored.Results Early results from three phase i/ii trials demonstrated that concurrent abiraterone acetate, adt, and rt is safe, improves the extent of chemical castration, and is associated with limited treatment failures. A single in vitro study implies synergy for radiosensitization beyond that facilitated by conventional adt. Studies investigating the combination of other arats with rt are under way, including multiple phase iii trials, but short-term results are not yet available.

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“…[14][15][16][17] Previous studies have demonstrated the efficacy and safety of ARTAs combined with radiotherapy in high-risk patients. [18][19][20] A few studies have shown that adding palliative radiotherapy to ARTA treatment in patients with oligoprogression prolongs the disease control during ARTA treatment. 21,22 However, the role of SBRT in oligoprogressive lesions during ARTA treatment and the effect of MDT on delaying NEST have yet to be investigated.…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have demonstrated the efficacy and safety of ARTAs combined with radiotherapy in high‐risk patients 18–20 . A few studies have shown that adding palliative radiotherapy to ARTA treatment in patients with oligoprogression prolongs the disease control during ARTA treatment 21,22 .…”

Section: Introductionmentioning

confidence: 99%

“…We treated relatively more oligoprogressive lesions (three on average) with ablative radiotherapy using SBRT and found comparable ARTA durations and PFS but fairly longer PCSS compared to previous studies.There are no clear data on the concurrent use of abiraterone or enzalutamide with radiotherapy. A few studies have, however, demonstrated the feasibility and safety of this modality in PC patients 20,40. Preclinical studies have shown that radiotherapy may enhance the effects of ARTAs by promoting cell death and stimulating the dying cells to release certain mediators that render cancer cells more vulnerable to immune-mediated cytotoxicity 41.…”

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confidence: 99%

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Stereotactic body radiotherapy for oligoprogressive lesions in metastatic castration‐resistant prostate cancer patients during abiraterone/enzalutamide treatment

et al. 2021

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Background: Metastasis-directed therapy (MDT) utilizing stereotactic body radiotherapy (SBRT) for oligoprogressive lesions could provide a delay in next-line systemic treatment (NEST) change while undergoing androgen receptor-targeted agents (ARTA) treatment. We evaluated prognostic factors for prostate cancerspecific survival (PCSS) and progression-free survival (PFS) to characterize patients receiving treatment with ARTA who may benefit from MDT for oligoprogressive lesions. The impact of MDT on delaying NEST and the predictive factors for NESTfree survival (NEST-FS) were also assessed. Materials and Methods:The clinical data of 54 metastatic castration-resistant prostate cancer patients with 126 oligoprogressive lesions receiving abiraterone (1 g/day) or enzalutamide (160 mg/day) before or after systemic chemotherapy were analyzed. A median of three lesions (range: 1-5) were treated with MDT. The primary endpoints were PCSS and PFS. The secondary endpoints were time to switch to NEST and NEST-FS.Results: The median follow-up time was 19.1 months. Univariate analysis showed that the number of oligoprogressive lesions treated with SBRT and the time between the start of ARTA treatment and oligoprogression were significant prognostic factors for PCSS, and the timing of ARTA treatment (before or after chemotherapy) and the prostate-specific antigen (PSA) response after MDT were significant prognostic factors for PFS. Multivariate analysis showed that early MDT for oligoprogressive lesions delivered less than 6 months after the beginning of ARTA and higher PSA levels after MDT were significant predictors of worse PCSS and PFS.The median total duration of ARTA treatment was 13.8 months. The median time between the start of ARTA treatment and the start of MDT for oligoprogressive lesions was 5.2 months, and MDT extended the ARTA treatment by 8.6 months on average. Thirty-two (59.3%) patients continued ARTA treatment after MDT. ARTA treatment after chemotherapy, early oligoprogression requiring MDT, and lower

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Combined abiraterone acetate plus prednisone, salvage prostate bed radiotherapy and LH-RH agonists (CARLHA-GEP12) in biochemically-relapsing prostate cancer patients following prostatectomy: A phase I study of the GETUG/GEP

Cited by 13 publications

References 29 publications

Outcome After 68Ga-PSMA-11 versus Choline PET-Based Salvage Radiotherapy in Patients with Biochemical Recurrence of Prostate Cancer: A Matched-Pair Analysis

Outcome After 68Ga-PSMA-11 versus Choline PET-Based Salvage Radiotherapy in Patients with Biochemical Recurrence of Prostate Cancer: A Matched-Pair Analysis

Combining Prostate Cancer Radiotherapy with Therapies Targeting the Androgen Receptor Axis

Stereotactic body radiotherapy for oligoprogressive lesions in metastatic castration‐resistant prostate cancer patients during abiraterone/enzalutamide treatment

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