Safety profile of sacituzumab govitecan in patients with breast cancer: A systematic review and meta-analysis
Background: Sacituzumab Govitecan (SG), a first-in-class anti-trophoblast cell surface antigen-2-directed antibody-drug conjugate (ADC), has shown clinically meaningful improvement in outcomes of patients with breast cancer (BC). However, it has also been accompanied by significant toxicity. Thus, w...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | Breast |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S096097762400184X |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823856925367861248 |
|---|---|
| author | Maria Inez Dacoregio Isabella Michelon Caio Ernesto do Rego Castro Francisco Cezar Aquino de Moraes Guilherme Rossato de Almeida Lis Victória Ravani Maysa Vilbert Ricardo Lima Barros Costa |
| author_facet | Maria Inez Dacoregio Isabella Michelon Caio Ernesto do Rego Castro Francisco Cezar Aquino de Moraes Guilherme Rossato de Almeida Lis Victória Ravani Maysa Vilbert Ricardo Lima Barros Costa |
| author_sort | Maria Inez Dacoregio |
| collection | DOAJ |
| description | Background: Sacituzumab Govitecan (SG), a first-in-class anti-trophoblast cell surface antigen-2-directed antibody-drug conjugate (ADC), has shown clinically meaningful improvement in outcomes of patients with breast cancer (BC). However, it has also been accompanied by significant toxicity. Thus, we conducted a systematic review and meta-analysis to evaluate the safety and tolerability of SG in this patient population. Methods: We comprehensively searched PubMed, Embase, and Cochrane databases, and ASCO and ESMO websites for clinical trials (CTs) assessing the safety of SG in BC patients. All analyses were performed in R software (v.4.2.2) using random effects models. Heterogeneity was assessed using I2 test. Results: Seven studies – three randomized clinical trials (RCTs) and four single-arm phase I/II – were included, comprising 928 patients receiving SG and 576 on treatment of physician's choice (TPC). Most patients had triple negative BC (54.4 %, n = 505), metastatic disease (89.8 %, n = 833), and were heavily pretreated (at least two lines of prior therapy). Most common all-grade adverse events (AEs) were: neutropenia (70 %, 95 % CI, 64–76 %), followed by nausea (62 %, 95 % CI, 55–68 %), diarrhea (54 %, 95 % CI 47–60 %) and anemia (51 %, 95 % CI, 38–65 %). Regarding high-grade AEs, 46 % of patients developed grade ≥3 neutropenia. Compared to TPC, we observed a higher risk of neutropenia (OR 3.11, 95 % CI 1.62–5.99, I2 = 81 %; p < 0.001), diarrhea (OR 6.82, 95 % CI 3.99–11.66, I2 = 64 %; p < 0.001) and anemia (OR 2.26, 95 % CI 1.20–4.27, I2 = 78 %; p = 0.012) for those on SG. Dose reductions and treatment discontinuation were reported in 22 % and 4 % of patients, respectively, and 19 deaths (2 %) were documented. Most of them were not deemed to be treated-related. Conclusion: This systematic review and meta-analysis provides extensive data on the safety and management of SG toxicity in BC patients across clinical trials. Concerning rates of neutropenia, nausea diarrhea, and anemia were reported. We highlight the need for protocols establishing prophylactic measures and strategies to mitigate SG-related toxicity. |
| format | Article |
| id | doaj-art-aac951681d6c4f5d84bdccd70cc30636 |
| institution | Kabale University |
| issn | 1532-3080 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Breast |
| spelling | doaj-art-aac951681d6c4f5d84bdccd70cc306362025-02-12T05:30:34ZengElsevierBreast1532-30802025-02-0179103853Safety profile of sacituzumab govitecan in patients with breast cancer: A systematic review and meta-analysisMaria Inez Dacoregio0Isabella Michelon1Caio Ernesto do Rego Castro2Francisco Cezar Aquino de Moraes3Guilherme Rossato de Almeida4Lis Victória Ravani5Maysa Vilbert6Ricardo Lima Barros Costa7Department of Medicine, University of Centro Oeste, Guarapuava, BrazilDepartment of Medicine, Catholic University of Pelotas, Pelotas, BrazilDepartment of Medicine, Universidade de Brasília, DF, BrazilDepartment of Medicine, Federal University of Pará, Pará, BrazilAC Camargo Cancer Center, São Paulo, SP, BrazilDepartment of Medicine, FMUSP Universidade de São Paulo, SP, BrazilMassachusetts General Hospital Cancer Center, Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USADepartment of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; Corresponding author. Department of Breast Oncology, H. Lee Moffitt Cancer Center 12902 Magnolia Drive, MKC-BRPROG Tampa, FL, 33612, USA.Background: Sacituzumab Govitecan (SG), a first-in-class anti-trophoblast cell surface antigen-2-directed antibody-drug conjugate (ADC), has shown clinically meaningful improvement in outcomes of patients with breast cancer (BC). However, it has also been accompanied by significant toxicity. Thus, we conducted a systematic review and meta-analysis to evaluate the safety and tolerability of SG in this patient population. Methods: We comprehensively searched PubMed, Embase, and Cochrane databases, and ASCO and ESMO websites for clinical trials (CTs) assessing the safety of SG in BC patients. All analyses were performed in R software (v.4.2.2) using random effects models. Heterogeneity was assessed using I2 test. Results: Seven studies – three randomized clinical trials (RCTs) and four single-arm phase I/II – were included, comprising 928 patients receiving SG and 576 on treatment of physician's choice (TPC). Most patients had triple negative BC (54.4 %, n = 505), metastatic disease (89.8 %, n = 833), and were heavily pretreated (at least two lines of prior therapy). Most common all-grade adverse events (AEs) were: neutropenia (70 %, 95 % CI, 64–76 %), followed by nausea (62 %, 95 % CI, 55–68 %), diarrhea (54 %, 95 % CI 47–60 %) and anemia (51 %, 95 % CI, 38–65 %). Regarding high-grade AEs, 46 % of patients developed grade ≥3 neutropenia. Compared to TPC, we observed a higher risk of neutropenia (OR 3.11, 95 % CI 1.62–5.99, I2 = 81 %; p < 0.001), diarrhea (OR 6.82, 95 % CI 3.99–11.66, I2 = 64 %; p < 0.001) and anemia (OR 2.26, 95 % CI 1.20–4.27, I2 = 78 %; p = 0.012) for those on SG. Dose reductions and treatment discontinuation were reported in 22 % and 4 % of patients, respectively, and 19 deaths (2 %) were documented. Most of them were not deemed to be treated-related. Conclusion: This systematic review and meta-analysis provides extensive data on the safety and management of SG toxicity in BC patients across clinical trials. Concerning rates of neutropenia, nausea diarrhea, and anemia were reported. We highlight the need for protocols establishing prophylactic measures and strategies to mitigate SG-related toxicity.http://www.sciencedirect.com/science/article/pii/S096097762400184XSacituzumab govitecanAntibody-drug conjugatesTROP-2IMMU-132Breast cancerSafety |
| spellingShingle | Maria Inez Dacoregio Isabella Michelon Caio Ernesto do Rego Castro Francisco Cezar Aquino de Moraes Guilherme Rossato de Almeida Lis Victória Ravani Maysa Vilbert Ricardo Lima Barros Costa Safety profile of sacituzumab govitecan in patients with breast cancer: A systematic review and meta-analysis Breast Sacituzumab govitecan Antibody-drug conjugates TROP-2 IMMU-132 Breast cancer Safety |
| title | Safety profile of sacituzumab govitecan in patients with breast cancer: A systematic review and meta-analysis |
| title_full | Safety profile of sacituzumab govitecan in patients with breast cancer: A systematic review and meta-analysis |
| title_fullStr | Safety profile of sacituzumab govitecan in patients with breast cancer: A systematic review and meta-analysis |
| title_full_unstemmed | Safety profile of sacituzumab govitecan in patients with breast cancer: A systematic review and meta-analysis |
| title_short | Safety profile of sacituzumab govitecan in patients with breast cancer: A systematic review and meta-analysis |
| title_sort | safety profile of sacituzumab govitecan in patients with breast cancer a systematic review and meta analysis |
| topic | Sacituzumab govitecan Antibody-drug conjugates TROP-2 IMMU-132 Breast cancer Safety |
| url | http://www.sciencedirect.com/science/article/pii/S096097762400184X |
| work_keys_str_mv | AT mariainezdacoregio safetyprofileofsacituzumabgovitecaninpatientswithbreastcancerasystematicreviewandmetaanalysis AT isabellamichelon safetyprofileofsacituzumabgovitecaninpatientswithbreastcancerasystematicreviewandmetaanalysis AT caioernestodoregocastro safetyprofileofsacituzumabgovitecaninpatientswithbreastcancerasystematicreviewandmetaanalysis AT franciscocezaraquinodemoraes safetyprofileofsacituzumabgovitecaninpatientswithbreastcancerasystematicreviewandmetaanalysis AT guilhermerossatodealmeida safetyprofileofsacituzumabgovitecaninpatientswithbreastcancerasystematicreviewandmetaanalysis AT lisvictoriaravani safetyprofileofsacituzumabgovitecaninpatientswithbreastcancerasystematicreviewandmetaanalysis AT maysavilbert safetyprofileofsacituzumabgovitecaninpatientswithbreastcancerasystematicreviewandmetaanalysis AT ricardolimabarroscosta safetyprofileofsacituzumabgovitecaninpatientswithbreastcancerasystematicreviewandmetaanalysis |