Durvalumab Plus Tremelimumab in Solid Tumors: A Systematic Review

Arru, Caterina; Miglio, Maria Rosaria De; Cossu, Antonio; Muroni, Maria Rosaria; Carru, Ciriaco; Zinellu, Angelo; Paliogiannis, Panagiotis

doi:10.1007/s12325-021-01796-6

Cited by 16 publications

(12 citation statements)

References 95 publications

(131 reference statements)

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“…The study also found no differences in treatment-related AEs between the two groups. In addition, a systematic review by Arru et al 16 focused on treatment efficacy and did not provide detailed data on AEs; therefore, data on AEs in DT-only regimens are required to establish the risks and benefits of DT therapy.…”

Section: Discussionmentioning

confidence: 99%

Adverse events induced by durvalumab and tremelimumab combination regimens: a systematic review and meta-analysis

Matsumoto,

Somekawa,

Horita

et al. 2023

Ther Adv Med Oncol

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Background: Immune checkpoint inhibitors (ICIs) have shown remarkable therapeutic outcomes among cancer patients. Durvalumab plus tremelimumab (DT) is under investigation as a new ICI combination therapy, and its efficacy has been reported in various types of cancer. However, the safety profile of DT remains unclear, especially considering rare adverse events (AEs). Objective: We aimed to assess the frequency of AEs associated with DT. Design: This study type is a systematic review and meta-analysis. Data Sources and Methods: Four databases were searched for articles. Randomized trials, single-arm trials, and prospective and retrospective observational studies were included. The type of cancer, previous treatment, and performance status were not questioned. Major AE indicators such as any AE and the pooled frequency of each specific AE were used as outcomes. As a subgroup analysis, we also compared cases in which DT was performed as first-line treatment with those in which it was performed as second-line or later treatment. The protocol for this systematic review was registered on the University Hospital Medical Information Network (UMIN) Center website (ID: UMIN000046751). Results: Forty-one populations including 3099 patients were selected from 30 articles. Pooled frequencies of key AE indicators are shown below: any AEs, 77.8% [95% confidence interval (CI): 67.9–87.6]; grade ⩾ 3 AEs, 29.3% (95% CI: 24.2–34.4); serious AEs, 34.9% (95% CI: 28.1–41.7); AE leading to discontinuation, 13.3% (95% CI: 9.3–17.4); treatment-related deaths, 0.98% (95% CI: 0.5–1.5). AEs with a frequency exceeding 15% are shown below: fatigue, 30.1% (95% CI: 23.8–36.3); diarrhea, 21.7% (95% CI: 17.8–25.6); pruritus 17.9% (95% CI: 14.4–21.3); decreased appetite, 17.7% (95% CI: 13.7–22.0); nausea, 15.6% (95% CI: 12.1–19.6). There were no significant differences in these pooled frequencies between subgroups. Conclusions: The incidence of any AE in DT therapy was approximately 78%, and the incidence of grade 3 or higher AEs was approximately 30%, which was independent of prior therapy.

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Section: Discussionmentioning

confidence: 99%

Adverse events induced by durvalumab and tremelimumab combination regimens: a systematic review and meta-analysis

Matsumoto,

Somekawa,

Horita

et al. 2023

Ther Adv Med Oncol

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“…Tremelimumab locates at the B7-1/2 binding site of CTLA-4, allowing CTLA-4 to bind more tightly to Tremelimumab. Therefore, Tremelimumab blocks the action of CTLA-4 in cancer by binding more closely to CTLA-4 than B7-1/2 [5] and ultimately achieving the purpose of treating cancer. The current study results showed that the use of Tremelimumab alone to treat tumors showed lower overall anti-tumor activity, which may be due to the different modes of Tremelimumab and traditional CTLA-4 antibodies.…”

Section: Mechanism Of Action Of Tremelimumab In Cancer Therapymentioning

confidence: 99%

Application and therapeutic mechanism of Durvalumab and Tremelimumab monotherapy or combination in tumor treatment

Hou,

Kochi,

et al. 2023

International Conference on Modern Medicine and Global Health (ICMMGH 2023)

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“…Along with ipilimumab, another anti-CTLA-4 antibody known as tremelimumab has entered clinical trials, but its antineoplastic activity was low while it was administered as a single drug, and it has also shown substantial side effects (the incidence of thyroid disorders is 0-5.2%). However, its association with durvalumab for treating mesothelioma, melanoma, NSCLC, gastroesophageal or colorectal tumors could be promising, even though some studies have not shown a substantial benefit added by tremelimumab compared to durvalumab alone (50)(51)(52). A phase 3 clinical trial (CheckMate 037) has shown that anti-PD-1 antibodies have both higher efficacy and a superior safety profile compared to ipilimumab (53).…”

Section: Fda-approved Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Thyroid-related adverse events induced by immune checkpoint inhibitors

2022

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Immune checkpoint inhibitors, namely anti-CTLA-4, anti-PD-1 and anti-PD-L1 monoclonal antibodies, have emerged in the last decade as a novel form of cancer treatment, promoting increased survival in patients. As they tamper with the immune response in order to destroy malignant cells, a new type of adverse reactions has emerged, known as immune-related adverse events (irAEs), which frequently target the endocrine system, especially the thyroid and hypophysis. Thyroid irAEs include hyperthyroidism, thyrotoxicosis, hypothyroidism and a possibly life-threatening condition known as the “thyroid storm”. Early prediction of occurrence and detection of the thyroid irAEs should be a priority for the clinician, in order to avoid critical situations. Moreover, they are recently considered both a prognostic marker and a means of overseeing treatment response, since they indicate an efficient activation of the immune system. Therefore, a multidisciplinary approach including both oncologists and endocrinologists is recommended when immune checkpoint inhibitors are used in the clinic.

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Durvalumab Plus Tremelimumab in Solid Tumors: A Systematic Review

Cited by 16 publications

References 95 publications

Adverse events induced by durvalumab and tremelimumab combination regimens: a systematic review and meta-analysis

Adverse events induced by durvalumab and tremelimumab combination regimens: a systematic review and meta-analysis

Application and therapeutic mechanism of Durvalumab and Tremelimumab monotherapy or combination in tumor treatment

Thyroid-related adverse events induced by immune checkpoint inhibitors

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