Associations with response to Poly(ADP-ribose) Polymerase (PARP) inhibitors in patients with metastatic breast cancer
Abstract PARP inhibitors (PARPi) have modest antitumor activity in patients with advanced breast cancer and mutation in BRCA. It is unclear whether some subgroups derive greater benefit from treatment. MEDLINE and EMBASE were searched from inception to March 2021 to identify trials of PARPi in patie...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-03-01
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| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-022-00405-1 |
| _version_ | 1797426950469320704 |
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| author | A. Desnoyers M. Nadler B. E. Wilson S. Stajer E. Amir |
| author_facet | A. Desnoyers M. Nadler B. E. Wilson S. Stajer E. Amir |
| author_sort | A. Desnoyers |
| collection | DOAJ |
| description | Abstract PARP inhibitors (PARPi) have modest antitumor activity in patients with advanced breast cancer and mutation in BRCA. It is unclear whether some subgroups derive greater benefit from treatment. MEDLINE and EMBASE were searched from inception to March 2021 to identify trials of PARPi in patients with metastatic breast cancer. Objective response rate (ORR) and clinical benefit rate (CBR) to PARPi were extracted and pooled in a meta-analysis using the Mantel Haenszel random effects model. Meta-regression explored the influence of patient and tumor characteristics on ORR and CBR. For randomized trials, hazard ratio comparing PARPi to control therapy were pooled using inverse variance and random effects. Analysis included 43 studies comprising 2409 patients. Among these, 1798 (75%) patients had BRCA mutations and 1146 (48%) were triple negative. In 10 studies (28%; n = 680 patients), the PARPi was given in combination with platinum-based chemotherapy. Weighted mean ORR was 45%; 64% when combined with platinum vs 37% with PARPi monotherapy (p < 0.001). Previous platinum-based chemotherapy was associated with lower ORR (p = 0.02). Compared to standard chemotherapy, progression-free survival was improved (HR 0.64, p < 0.001), but there was no difference in overall survival (HR 0.87, p = 0.06). There were no differences in ORR or CBR between BRCA1 and BRCA2 mutations. PARPi are more active in combination with platinum than as monotherapy, with lower response if given as monotherapy after platinum exposure. Significant improvements in ORR translated to modest improvement in progression-free, but not overall survival. There was no association between ORR and BRCA mutations. |
| first_indexed | 2024-03-09T08:37:16Z |
| format | Article |
| id | doaj.art-d3d706c2421047dc86bf84b328cad73f |
| institution | Directory Open Access Journal |
| issn | 2374-4677 |
| language | English |
| last_indexed | 2024-03-09T08:37:16Z |
| publishDate | 2022-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Breast Cancer |
| spelling | doaj.art-d3d706c2421047dc86bf84b328cad73f2023-12-02T18:03:34ZengNature Portfolionpj Breast Cancer2374-46772022-03-018111010.1038/s41523-022-00405-1Associations with response to Poly(ADP-ribose) Polymerase (PARP) inhibitors in patients with metastatic breast cancerA. Desnoyers0M. Nadler1B. E. Wilson2S. Stajer3E. Amir4Division of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and the University of TorontoDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and the University of TorontoDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and the University of TorontoDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and the University of TorontoDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and the University of TorontoAbstract PARP inhibitors (PARPi) have modest antitumor activity in patients with advanced breast cancer and mutation in BRCA. It is unclear whether some subgroups derive greater benefit from treatment. MEDLINE and EMBASE were searched from inception to March 2021 to identify trials of PARPi in patients with metastatic breast cancer. Objective response rate (ORR) and clinical benefit rate (CBR) to PARPi were extracted and pooled in a meta-analysis using the Mantel Haenszel random effects model. Meta-regression explored the influence of patient and tumor characteristics on ORR and CBR. For randomized trials, hazard ratio comparing PARPi to control therapy were pooled using inverse variance and random effects. Analysis included 43 studies comprising 2409 patients. Among these, 1798 (75%) patients had BRCA mutations and 1146 (48%) were triple negative. In 10 studies (28%; n = 680 patients), the PARPi was given in combination with platinum-based chemotherapy. Weighted mean ORR was 45%; 64% when combined with platinum vs 37% with PARPi monotherapy (p < 0.001). Previous platinum-based chemotherapy was associated with lower ORR (p = 0.02). Compared to standard chemotherapy, progression-free survival was improved (HR 0.64, p < 0.001), but there was no difference in overall survival (HR 0.87, p = 0.06). There were no differences in ORR or CBR between BRCA1 and BRCA2 mutations. PARPi are more active in combination with platinum than as monotherapy, with lower response if given as monotherapy after platinum exposure. Significant improvements in ORR translated to modest improvement in progression-free, but not overall survival. There was no association between ORR and BRCA mutations.https://doi.org/10.1038/s41523-022-00405-1 |
| spellingShingle | A. Desnoyers M. Nadler B. E. Wilson S. Stajer E. Amir Associations with response to Poly(ADP-ribose) Polymerase (PARP) inhibitors in patients with metastatic breast cancer npj Breast Cancer |
| title | Associations with response to Poly(ADP-ribose) Polymerase (PARP) inhibitors in patients with metastatic breast cancer |
| title_full | Associations with response to Poly(ADP-ribose) Polymerase (PARP) inhibitors in patients with metastatic breast cancer |
| title_fullStr | Associations with response to Poly(ADP-ribose) Polymerase (PARP) inhibitors in patients with metastatic breast cancer |
| title_full_unstemmed | Associations with response to Poly(ADP-ribose) Polymerase (PARP) inhibitors in patients with metastatic breast cancer |
| title_short | Associations with response to Poly(ADP-ribose) Polymerase (PARP) inhibitors in patients with metastatic breast cancer |
| title_sort | associations with response to poly adp ribose polymerase parp inhibitors in patients with metastatic breast cancer |
| url | https://doi.org/10.1038/s41523-022-00405-1 |
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