PARP inhibitor‐based treatment in metastatic, castration‐resistant prostate cancer (mCRPC): A systematic review and meta‐analysis
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| Format: | Artículo Open Access |
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Wiley
2025
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| _version_ | 1867010819273785344 |
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| author | Michela Roberto Mattia Alberto Di Civita Daniele Marinelli Andrea Torchia Nertila Cara Giulia Maltese Iolanda Speranza Daniele Santini |
| author_facet | Michela Roberto Mattia Alberto Di Civita Daniele Marinelli Andrea Torchia Nertila Cara Giulia Maltese Iolanda Speranza Daniele Santini Michela Roberto Mattia Alberto Di Civita Daniele Marinelli Andrea Torchia Nertila Cara Giulia Maltese Iolanda Speranza Daniele Santini |
| collection | Wiley Open Access |
| contents | PARP inhibitor‐based treatment in metastatic, castration‐resistant prostate cancer (mCRPC): A systematic review and meta‐analysis Michela Roberto Mattia Alberto Di Civita Daniele Marinelli Andrea Torchia Nertila Cara Giulia Maltese Iolanda Speranza Daniele Santini BJUI Compass AbstractBackgroundWe present a systematic review and meta‐analysis of randomized clinical trials (RCTs) with PARPi either as monotherapy or in combination with an androgen receptor‐targeted agent (ARTA) in first‐ and second‐line settings.MethodsPrimary endpoints are radiographic progression free survival (rPFS) and overall survival (OS) in patients with mCRPC and either unselected, homologous recombination repair wild‐type (HRR−), homologous recombination repair mutated (HRR+) or with BRCA1, BRCA2, or ATM mutation. The effect of PARPi + ARTA in the second‐line setting is also explored. Safety is a secondary end‐point.ResultsA total of five phase III (first line: MAGNITUDE, PROpel, TALAPRO‐2; second line: PROfound, TRITON3) and two phase II RCTs (second line: NCT01972217, NCT01576172) were selected. In the first‐line setting, rPFS was significantly improved in PARPi + ARTA arm in all comers (HR 0.70, p < 0.00001), HRR− (HR 0.76, p = 0.005), HRR+ (HR 0.57, p = 0.0003), and BRCA1/2‐mutated patients (HR: 0.33, p < 0.00001). OS was improved in the population with HRR+ status (HR 0.76, p = 0.02) but not statistically significant in BRCA1/2‐mutated patients (HR 0.57, 95% CI 0.30–1.08, p = 0.08). In the second line, PARPi improves rPFS (HR for BRCA2 0.31, p = 0.002) and OS (HR for BRCA1/2 0.71, p = 0.01) only in such patients. In this setting, no advantage was reported by adding a PARPi to an ARTA. The arm with PARPi either as monotherapy or in combination with ARTA showed a significantly higher toxicity profile.ConclusionsPARPi‐based therapy represents a compelling treatment option for HRR+ mCRPC, mainly BRCA1/2‐mutated patients. However, further biomarker analysis are needed in order to identify other responsive patients across the different disease settings. 10.1002/bco2.455 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1002/bco2.455 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_bco2_455 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | PARP inhibitor‐based treatment in metastatic, castration‐resistant prostate cancer (mCRPC): A systematic review and meta‐analysis Michela Roberto Mattia Alberto Di Civita Daniele Marinelli Andrea Torchia Nertila Cara Giulia Maltese Iolanda Speranza Daniele Santini BJUI Compass PARP inhibitor‐based treatment in metastatic, castration‐resistant prostate cancer (mCRPC): A systematic review and meta‐analysis Michela Roberto Mattia Alberto Di Civita Daniele Marinelli Andrea Torchia Nertila Cara Giulia Maltese Iolanda Speranza Daniele Santini BJUI Compass AbstractBackgroundWe present a systematic review and meta‐analysis of randomized clinical trials (RCTs) with PARPi either as monotherapy or in combination with an androgen receptor‐targeted agent (ARTA) in first‐ and second‐line settings.MethodsPrimary endpoints are radiographic progression free survival (rPFS) and overall survival (OS) in patients with mCRPC and either unselected, homologous recombination repair wild‐type (HRR−), homologous recombination repair mutated (HRR+) or with BRCA1, BRCA2, or ATM mutation. The effect of PARPi + ARTA in the second‐line setting is also explored. Safety is a secondary end‐point.ResultsA total of five phase III (first line: MAGNITUDE, PROpel, TALAPRO‐2; second line: PROfound, TRITON3) and two phase II RCTs (second line: NCT01972217, NCT01576172) were selected. In the first‐line setting, rPFS was significantly improved in PARPi + ARTA arm in all comers (HR 0.70, p < 0.00001), HRR− (HR 0.76, p = 0.005), HRR+ (HR 0.57, p = 0.0003), and BRCA1/2‐mutated patients (HR: 0.33, p < 0.00001). OS was improved in the population with HRR+ status (HR 0.76, p = 0.02) but not statistically significant in BRCA1/2‐mutated patients (HR 0.57, 95% CI 0.30–1.08, p = 0.08). In the second line, PARPi improves rPFS (HR for BRCA2 0.31, p = 0.002) and OS (HR for BRCA1/2 0.71, p = 0.01) only in such patients. In this setting, no advantage was reported by adding a PARPi to an ARTA. The arm with PARPi either as monotherapy or in combination with ARTA showed a significantly higher toxicity profile.ConclusionsPARPi‐based therapy represents a compelling treatment option for HRR+ mCRPC, mainly BRCA1/2‐mutated patients. However, further biomarker analysis are needed in order to identify other responsive patients across the different disease settings. 10.1002/bco2.455 http://creativecommons.org/licenses/by/4.0/ |
| title | PARP inhibitor‐based treatment in metastatic, castration‐resistant prostate cancer (mCRPC): A systematic review and meta‐analysis |
| topic | BJUI Compass |
| url | https://bjui-journals.onlinelibrary.wiley.com/doi/10.1002/bco2.455 |