Comparative efficacy and safety of PD-1/PD-L1 inhibitors in triple negative breast cancer: a systematic review and network meta-analysis of randomized controlled trials
<h3>Background</h3><p dir="ltr">Triple-Negative Breast Cancer (TNBC) is a lethal subtype of breast cancer with limited treatment options. The purpose of this Network Meta-Analysis (NMA) is to compare the efficacy and safety of inhibitors of programmed cell death 1 (PD-1)...
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| مؤلفون آخرون: | , , , |
| منشور في: |
2023
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إضافة وسم
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| _version_ | 1864513526867951616 |
|---|---|
| author | Ibrahim Elmakaty (14614270) |
| author2 | Ruba Abdo (15455318) Ahmed Elsabagh (15455321) Abdelrahman Elsayed (6288913) Mohammed Imad Malki (9649555) |
| author2_role | author author author author |
| author_facet | Ibrahim Elmakaty (14614270) Ruba Abdo (15455318) Ahmed Elsabagh (15455321) Abdelrahman Elsayed (6288913) Mohammed Imad Malki (9649555) |
| author_role | author |
| dc.creator.none.fl_str_mv | Ibrahim Elmakaty (14614270) Ruba Abdo (15455318) Ahmed Elsabagh (15455321) Abdelrahman Elsayed (6288913) Mohammed Imad Malki (9649555) |
| dc.date.none.fl_str_mv | 2023-05-11T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1186/s12935-023-02941-7 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Comparative_efficacy_and_safety_of_PD-1_PD-L1_inhibitors_in_triple_negative_breast_cancer_a_systematic_review_and_network_meta-analysis_of_randomized_controlled_trials/25256683 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Oncology and carcinogenesis PD-1/PD-L1 inhibitors Immune checkpoint inhibitors Overall survival Progression-free survival Pathological complete response Adverse events Efcacy Safety Systematic review Network meta-analysis |
| dc.title.none.fl_str_mv | Comparative efficacy and safety of PD-1/PD-L1 inhibitors in triple negative breast cancer: a systematic review and network meta-analysis of randomized controlled trials |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <h3>Background</h3><p dir="ltr">Triple-Negative Breast Cancer (TNBC) is a lethal subtype of breast cancer with limited treatment options. The purpose of this Network Meta-Analysis (NMA) is to compare the efficacy and safety of inhibitors of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in treating TNBC.</p><h3>Methods</h3><p dir="ltr">Our search strategy was used in six databases: PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature database, Embase, Scopus, and Web of Science up to November 2nd, 2022, as well as a thorough search in the most used trial registries. We included phase II and III randomized controlled trials that looked at the efficacy of PD-1/PD-L1 inhibitors in the treatment of TNBC and reported either Overall Survival (OS), Progression-Free Survival (PFS), or pathological Complete Response (pCR). The risk of bias was assessed utilizing Cochrane's risk of bias 2 tool, and the statistical analysis was performed using a frequentist contrast-based method for NMA by employing standard pairwise meta-analysis applying random effects model.</p><h3>Results</h3><p dir="ltr">12 trials (5324 patients) were included in our NMA including seven phase III trials. Pembrolizumab in a neoadjuvant setting achieved a pooled OS of 0.82 (95% Confidence Interval (CI) 0.65 to 1.03), a PFS of 0.82 (95% CI 0.71 to 0.94) and a pCR 2.79 (95% CI 1.07 to 7.24) compared to Atezolizumab’s OS of 0.92 (95% CI 0.74 to 1.15), PFS of 0.82 (95% CI 0.69 to 0.97), and pCR of 1.94 (95% CI 0.86 to 4.37). Atezolizumab had less grade ≥ 3 adverse events (OR 1.48, 95% CI 0.90 to 2.42) than Pembrolizumab (OR 1.90, 95% CI 1.08 to 3.33) in the neoadjuvant setting.</p><h3>Conclusions</h3><p dir="ltr">PD-1/PD-L1 inhibitors exhibited varying efficacy in terms of OS, PFS, and pCR. They were associated with an increase in immune-related adverse effects. When used early in the course of TNBC, PD-1/PD-L1 inhibitors exert their maximum benefit. Durvalumab as a maintenance treatment instead of chemotherapy has shown promising outcomes. Future studies should focus on PD-L1 expression status and TNBC subtypes, since these factors may contribute to the design of individualized TNBC therapy regimens.</p><p dir="ltr">Systematic review registration PROSPERO Identifier: CRD42022380712.</p><h2>Other Information</h2><p dir="ltr">Published in: Cancer Cell International<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s12935-023-02941-7" target="_blank">https://dx.doi.org/10.1186/s12935-023-02941-7</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_b86c4364139587bdab11a69a6b6b9d94 |
| identifier_str_mv | 10.1186/s12935-023-02941-7 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25256683 |
| publishDate | 2023 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Comparative efficacy and safety of PD-1/PD-L1 inhibitors in triple negative breast cancer: a systematic review and network meta-analysis of randomized controlled trialsIbrahim Elmakaty (14614270)Ruba Abdo (15455318)Ahmed Elsabagh (15455321)Abdelrahman Elsayed (6288913)Mohammed Imad Malki (9649555)Biological sciencesGeneticsBiomedical and clinical sciencesOncology and carcinogenesisPD-1/PD-L1 inhibitorsImmune checkpoint inhibitorsOverall survivalProgression-free survivalPathological complete responseAdverse eventsEfcacySafetySystematic reviewNetwork meta-analysis<h3>Background</h3><p dir="ltr">Triple-Negative Breast Cancer (TNBC) is a lethal subtype of breast cancer with limited treatment options. The purpose of this Network Meta-Analysis (NMA) is to compare the efficacy and safety of inhibitors of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in treating TNBC.</p><h3>Methods</h3><p dir="ltr">Our search strategy was used in six databases: PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature database, Embase, Scopus, and Web of Science up to November 2nd, 2022, as well as a thorough search in the most used trial registries. We included phase II and III randomized controlled trials that looked at the efficacy of PD-1/PD-L1 inhibitors in the treatment of TNBC and reported either Overall Survival (OS), Progression-Free Survival (PFS), or pathological Complete Response (pCR). The risk of bias was assessed utilizing Cochrane's risk of bias 2 tool, and the statistical analysis was performed using a frequentist contrast-based method for NMA by employing standard pairwise meta-analysis applying random effects model.</p><h3>Results</h3><p dir="ltr">12 trials (5324 patients) were included in our NMA including seven phase III trials. Pembrolizumab in a neoadjuvant setting achieved a pooled OS of 0.82 (95% Confidence Interval (CI) 0.65 to 1.03), a PFS of 0.82 (95% CI 0.71 to 0.94) and a pCR 2.79 (95% CI 1.07 to 7.24) compared to Atezolizumab’s OS of 0.92 (95% CI 0.74 to 1.15), PFS of 0.82 (95% CI 0.69 to 0.97), and pCR of 1.94 (95% CI 0.86 to 4.37). Atezolizumab had less grade ≥ 3 adverse events (OR 1.48, 95% CI 0.90 to 2.42) than Pembrolizumab (OR 1.90, 95% CI 1.08 to 3.33) in the neoadjuvant setting.</p><h3>Conclusions</h3><p dir="ltr">PD-1/PD-L1 inhibitors exhibited varying efficacy in terms of OS, PFS, and pCR. They were associated with an increase in immune-related adverse effects. When used early in the course of TNBC, PD-1/PD-L1 inhibitors exert their maximum benefit. Durvalumab as a maintenance treatment instead of chemotherapy has shown promising outcomes. Future studies should focus on PD-L1 expression status and TNBC subtypes, since these factors may contribute to the design of individualized TNBC therapy regimens.</p><p dir="ltr">Systematic review registration PROSPERO Identifier: CRD42022380712.</p><h2>Other Information</h2><p dir="ltr">Published in: Cancer Cell International<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s12935-023-02941-7" target="_blank">https://dx.doi.org/10.1186/s12935-023-02941-7</a></p>2023-05-11T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1186/s12935-023-02941-7https://figshare.com/articles/journal_contribution/Comparative_efficacy_and_safety_of_PD-1_PD-L1_inhibitors_in_triple_negative_breast_cancer_a_systematic_review_and_network_meta-analysis_of_randomized_controlled_trials/25256683CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/252566832023-05-11T03:00:00Z |
| spellingShingle | Comparative efficacy and safety of PD-1/PD-L1 inhibitors in triple negative breast cancer: a systematic review and network meta-analysis of randomized controlled trials Ibrahim Elmakaty (14614270) Biological sciences Genetics Biomedical and clinical sciences Oncology and carcinogenesis PD-1/PD-L1 inhibitors Immune checkpoint inhibitors Overall survival Progression-free survival Pathological complete response Adverse events Efcacy Safety Systematic review Network meta-analysis |
| status_str | publishedVersion |
| title | Comparative efficacy and safety of PD-1/PD-L1 inhibitors in triple negative breast cancer: a systematic review and network meta-analysis of randomized controlled trials |
| title_full | Comparative efficacy and safety of PD-1/PD-L1 inhibitors in triple negative breast cancer: a systematic review and network meta-analysis of randomized controlled trials |
| title_fullStr | Comparative efficacy and safety of PD-1/PD-L1 inhibitors in triple negative breast cancer: a systematic review and network meta-analysis of randomized controlled trials |
| title_full_unstemmed | Comparative efficacy and safety of PD-1/PD-L1 inhibitors in triple negative breast cancer: a systematic review and network meta-analysis of randomized controlled trials |
| title_short | Comparative efficacy and safety of PD-1/PD-L1 inhibitors in triple negative breast cancer: a systematic review and network meta-analysis of randomized controlled trials |
| title_sort | Comparative efficacy and safety of PD-1/PD-L1 inhibitors in triple negative breast cancer: a systematic review and network meta-analysis of randomized controlled trials |
| topic | Biological sciences Genetics Biomedical and clinical sciences Oncology and carcinogenesis PD-1/PD-L1 inhibitors Immune checkpoint inhibitors Overall survival Progression-free survival Pathological complete response Adverse events Efcacy Safety Systematic review Network meta-analysis |