Efficacy and safety of PD-1 and PD-L1 inhibitors combined with chemotherapy in randomized clinical trials among triple-negative breast cancer
Background: The combination of immune checkpoint inhibitors (ICIs) and chemotherapy (CT) is a new strategy to explore cancer treatment in recent years, and it is also practiced in triple-negative breast cancer (TNBC). However, several published randomized controlled trials (RCTs) reported heterogene...
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| Format: | Article |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.960323/full |
| _version_ | 1797995207030996992 |
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| author | Yihang Qi Yihang Qi Wenxiang Zhang Ray Jiang Olivia Xu Xiangyi Kong Lin Zhang Lin Zhang Lin Zhang Yi Fang Jingping Wang Jing Wang |
| author_facet | Yihang Qi Yihang Qi Wenxiang Zhang Ray Jiang Olivia Xu Xiangyi Kong Lin Zhang Lin Zhang Lin Zhang Yi Fang Jingping Wang Jing Wang |
| author_sort | Yihang Qi |
| collection | DOAJ |
| description | Background: The combination of immune checkpoint inhibitors (ICIs) and chemotherapy (CT) is a new strategy to explore cancer treatment in recent years, and it is also practiced in triple-negative breast cancer (TNBC). However, several published randomized controlled trials (RCTs) reported heterogeneous results. We conducted this meta-analysis to yield insights into the efficacy and safety of the combination of ICIs and CT for TNBC patients in both the adjuvant and neoadjuvant settings.Method: EMBASE, PUBMED, Cochrane, and www.clinicaltrials.gov databases were searched to determine potential eligible studies from the inception to 20 May 2022. Published RCTs on PD-1/PD-L1 ICIs combined with CT for TNBC patients were included.Result: This meta-analysis included six double-blind RCTs comprising 4,081 TNBC patients treated with PD-1 or PD-L1 ICIs plus CT or placebo plus CT. The combination strategy benefited a better pathologic complete response (pCR) by 29% (RR = 1.29; 95% CI: 1.17–1.41; I2 = 0%) and a better progression-free survival (PFS) (HR = 0.82; 95% CI: 0.74–0.90; I2 = 0%) in the neoadjuvant and the adjuvant settings, respectively, especially in PD-L1-positive population (HR = 0.71; 95% CI: 0.62–0.81; I2 = 13%). The safety profiles were generally tolerable in both settings but the combination treatment will increase the risk of severe adverse events in the adjuvant setting (RR = 1.33; 95% CI 1.08–1.62, I2 = 0%). Additionally, the combination will increase the risk of any-grade hypothyroidism, hyperthyroidism, pneumonia, and rash in the adjuvant setting, and the risk of any-grade hypothyroidism, hyperthyroidism, infusion-related reactions, and severe cutaneous reactions in the neoadjuvant setting.Conclusion: This meta-analysis demonstrated a significant pCR benefit and confirms the PFS benefit with PD-1/PD-L1 ICIs plus CT in TNBC patients with tolerable safety events in both neoadjuvant and adjuvant settings. |
| first_indexed | 2024-04-11T09:57:44Z |
| format | Article |
| id | doaj.art-e03066709672448dae46c21756b089d2 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T09:57:44Z |
| publishDate | 2022-09-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-e03066709672448dae46c21756b089d22022-12-22T04:30:31ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-09-011310.3389/fphar.2022.960323960323Efficacy and safety of PD-1 and PD-L1 inhibitors combined with chemotherapy in randomized clinical trials among triple-negative breast cancerYihang Qi0Yihang Qi1Wenxiang Zhang2Ray Jiang3Olivia Xu4Xiangyi Kong5Lin Zhang6Lin Zhang7Lin Zhang8Yi Fang9Jingping Wang10Jing Wang11Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesDepartment of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesDepartment of Neurology, New York University Grossman School of Medicine, New York City, NY, United StatesDepartment of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaSchool of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaMelbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, AustraliaCentre of Cancer Research, Victorian Comprehensive Cancer Centre, Melbourne, VIC, AustraliaDepartment of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesDepartment of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBackground: The combination of immune checkpoint inhibitors (ICIs) and chemotherapy (CT) is a new strategy to explore cancer treatment in recent years, and it is also practiced in triple-negative breast cancer (TNBC). However, several published randomized controlled trials (RCTs) reported heterogeneous results. We conducted this meta-analysis to yield insights into the efficacy and safety of the combination of ICIs and CT for TNBC patients in both the adjuvant and neoadjuvant settings.Method: EMBASE, PUBMED, Cochrane, and www.clinicaltrials.gov databases were searched to determine potential eligible studies from the inception to 20 May 2022. Published RCTs on PD-1/PD-L1 ICIs combined with CT for TNBC patients were included.Result: This meta-analysis included six double-blind RCTs comprising 4,081 TNBC patients treated with PD-1 or PD-L1 ICIs plus CT or placebo plus CT. The combination strategy benefited a better pathologic complete response (pCR) by 29% (RR = 1.29; 95% CI: 1.17–1.41; I2 = 0%) and a better progression-free survival (PFS) (HR = 0.82; 95% CI: 0.74–0.90; I2 = 0%) in the neoadjuvant and the adjuvant settings, respectively, especially in PD-L1-positive population (HR = 0.71; 95% CI: 0.62–0.81; I2 = 13%). The safety profiles were generally tolerable in both settings but the combination treatment will increase the risk of severe adverse events in the adjuvant setting (RR = 1.33; 95% CI 1.08–1.62, I2 = 0%). Additionally, the combination will increase the risk of any-grade hypothyroidism, hyperthyroidism, pneumonia, and rash in the adjuvant setting, and the risk of any-grade hypothyroidism, hyperthyroidism, infusion-related reactions, and severe cutaneous reactions in the neoadjuvant setting.Conclusion: This meta-analysis demonstrated a significant pCR benefit and confirms the PFS benefit with PD-1/PD-L1 ICIs plus CT in TNBC patients with tolerable safety events in both neoadjuvant and adjuvant settings.https://www.frontiersin.org/articles/10.3389/fphar.2022.960323/fullbreast cancerimmunotherapyPD-1/PD-L1 immune checkpoint inhibitorschemotherapyadjuvant therapyneoadjuvant therapy |
| spellingShingle | Yihang Qi Yihang Qi Wenxiang Zhang Ray Jiang Olivia Xu Xiangyi Kong Lin Zhang Lin Zhang Lin Zhang Yi Fang Jingping Wang Jing Wang Efficacy and safety of PD-1 and PD-L1 inhibitors combined with chemotherapy in randomized clinical trials among triple-negative breast cancer Frontiers in Pharmacology breast cancer immunotherapy PD-1/PD-L1 immune checkpoint inhibitors chemotherapy adjuvant therapy neoadjuvant therapy |
| title | Efficacy and safety of PD-1 and PD-L1 inhibitors combined with chemotherapy in randomized clinical trials among triple-negative breast cancer |
| title_full | Efficacy and safety of PD-1 and PD-L1 inhibitors combined with chemotherapy in randomized clinical trials among triple-negative breast cancer |
| title_fullStr | Efficacy and safety of PD-1 and PD-L1 inhibitors combined with chemotherapy in randomized clinical trials among triple-negative breast cancer |
| title_full_unstemmed | Efficacy and safety of PD-1 and PD-L1 inhibitors combined with chemotherapy in randomized clinical trials among triple-negative breast cancer |
| title_short | Efficacy and safety of PD-1 and PD-L1 inhibitors combined with chemotherapy in randomized clinical trials among triple-negative breast cancer |
| title_sort | efficacy and safety of pd 1 and pd l1 inhibitors combined with chemotherapy in randomized clinical trials among triple negative breast cancer |
| topic | breast cancer immunotherapy PD-1/PD-L1 immune checkpoint inhibitors chemotherapy adjuvant therapy neoadjuvant therapy |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.960323/full |
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