Risk of hepatotoxicity with trastuzumab emtansine in breast cancer patients: a systematic review and meta-analysis
Background: Trastuzumab emtansine (T-DM1) is an anti-HER2 antibody-drug conjugate indicated for the treatment of HER2-positive breast cancer. One of the most severe adverse events reported with T-DM1 is hepatotoxicity. The objective of our meta-analysis is to investigate the risk of hepatic adverse...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2020-04-01
|
| Series: | Therapeutic Advances in Drug Safety |
| Online Access: | https://doi.org/10.1177/2042098620915058 |
| _version_ | 1818849325908754432 |
|---|---|
| author | Amani M. Cobert Catherine Helms Chris Larck Donald C. Moore |
| author_facet | Amani M. Cobert Catherine Helms Chris Larck Donald C. Moore |
| author_sort | Amani M. Cobert |
| collection | DOAJ |
| description | Background: Trastuzumab emtansine (T-DM1) is an anti-HER2 antibody-drug conjugate indicated for the treatment of HER2-positive breast cancer. One of the most severe adverse events reported with T-DM1 is hepatotoxicity. The objective of our meta-analysis is to investigate the risk of hepatic adverse events in patients with breast cancer receiving T-DM1 compared with controls. Methods: We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) comparing T-DM1 with a control treatment in patients with HER2-positive breast cancer. Phase II/III RCTs with available event number or event rate of hepatic toxicity with an assessable sample size were included. Relative risk (RR) and corresponding 95% confidence intervals (CI) for all grade and high-grade (grade 3/4) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) elevations were calculated. Results: Seven RCTs were deemed eligible and were included in the meta-analysis. The RR for all-grade AST and ALT elevations were 3.24 (95% CI 2.16–4.86; p < 0.00001) and 2.90 (95% CI 1.98–4.23; p < 0.00001), respectively. The RR for high-grade AST and ALT elevations were 2.73 (95% CI 1.07–6.93; p = 0.03) and 2.17 (95% CI 1.34–3.50; p = 0.002), respectively. Conclusions: Our meta-analysis demonstrates that T-DM1-based therapy is associated with an increased risk of AST and ALT elevations. |
| first_indexed | 2024-12-19T06:31:27Z |
| format | Article |
| id | doaj.art-fd0fc3d6ef0d4f8785bf4a238dacf350 |
| institution | Directory Open Access Journal |
| issn | 2042-0994 |
| language | English |
| last_indexed | 2024-12-19T06:31:27Z |
| publishDate | 2020-04-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Drug Safety |
| spelling | doaj.art-fd0fc3d6ef0d4f8785bf4a238dacf3502022-12-21T20:32:24ZengSAGE PublishingTherapeutic Advances in Drug Safety2042-09942020-04-011110.1177/2042098620915058Risk of hepatotoxicity with trastuzumab emtansine in breast cancer patients: a systematic review and meta-analysisAmani M. CobertCatherine HelmsChris LarckDonald C. MooreBackground: Trastuzumab emtansine (T-DM1) is an anti-HER2 antibody-drug conjugate indicated for the treatment of HER2-positive breast cancer. One of the most severe adverse events reported with T-DM1 is hepatotoxicity. The objective of our meta-analysis is to investigate the risk of hepatic adverse events in patients with breast cancer receiving T-DM1 compared with controls. Methods: We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) comparing T-DM1 with a control treatment in patients with HER2-positive breast cancer. Phase II/III RCTs with available event number or event rate of hepatic toxicity with an assessable sample size were included. Relative risk (RR) and corresponding 95% confidence intervals (CI) for all grade and high-grade (grade 3/4) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) elevations were calculated. Results: Seven RCTs were deemed eligible and were included in the meta-analysis. The RR for all-grade AST and ALT elevations were 3.24 (95% CI 2.16–4.86; p < 0.00001) and 2.90 (95% CI 1.98–4.23; p < 0.00001), respectively. The RR for high-grade AST and ALT elevations were 2.73 (95% CI 1.07–6.93; p = 0.03) and 2.17 (95% CI 1.34–3.50; p = 0.002), respectively. Conclusions: Our meta-analysis demonstrates that T-DM1-based therapy is associated with an increased risk of AST and ALT elevations.https://doi.org/10.1177/2042098620915058 |
| spellingShingle | Amani M. Cobert Catherine Helms Chris Larck Donald C. Moore Risk of hepatotoxicity with trastuzumab emtansine in breast cancer patients: a systematic review and meta-analysis Therapeutic Advances in Drug Safety |
| title | Risk of hepatotoxicity with trastuzumab emtansine in breast cancer patients: a systematic review and meta-analysis |
| title_full | Risk of hepatotoxicity with trastuzumab emtansine in breast cancer patients: a systematic review and meta-analysis |
| title_fullStr | Risk of hepatotoxicity with trastuzumab emtansine in breast cancer patients: a systematic review and meta-analysis |
| title_full_unstemmed | Risk of hepatotoxicity with trastuzumab emtansine in breast cancer patients: a systematic review and meta-analysis |
| title_short | Risk of hepatotoxicity with trastuzumab emtansine in breast cancer patients: a systematic review and meta-analysis |
| title_sort | risk of hepatotoxicity with trastuzumab emtansine in breast cancer patients a systematic review and meta analysis |
| url | https://doi.org/10.1177/2042098620915058 |
| work_keys_str_mv | AT amanimcobert riskofhepatotoxicitywithtrastuzumabemtansineinbreastcancerpatientsasystematicreviewandmetaanalysis AT catherinehelms riskofhepatotoxicitywithtrastuzumabemtansineinbreastcancerpatientsasystematicreviewandmetaanalysis AT chrislarck riskofhepatotoxicitywithtrastuzumabemtansineinbreastcancerpatientsasystematicreviewandmetaanalysis AT donaldcmoore riskofhepatotoxicitywithtrastuzumabemtansineinbreastcancerpatientsasystematicreviewandmetaanalysis |