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Effekten och säkerheten av pembrolizumab vid behandling av trippelnegativ bröstcancer / The efficacy and safety of pembrolizumab in the treatment of triple-negative breast cancer.Ramhormozi Hassanizadeh, Anahita January 2024 (has links)
About 12 to 17 percent of all breast cancers are triple-negative breast cancer (TNBC). In TNBC, estrogen, progesterone, and human epidermal growth factor receptor two are not expressed, or copies of the HER2 gene are decreased (or both). This makes TNBC hard to treat in comparison with other kinds of breast cancers. New studies have made some interesting observations on how some monoclonal antibodies can help to treat TNBC. One of the monoclonal antibodies that can be useful for treating TNBC is pembrolizumab. Pembrolizumab inhibits programmed death ligand 1 (PD-1), which is located on the surface of T cells from connecting to immune checkpoint proteins such as programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2) located on the surface of the cancer cell. Breaking this connection enables continued activation of T cells and attack of the cancer cells. This thesis aimed to evaluate if pembrolizumab was safe and effective as monotherapy or as a combination therapy with chemotherapy for patients with different stages of TNBC. This study was based on scientific articles identified from the database PubMed. Five randomized controlled trial studies were selected for further study in this project. Two publications were chosen from keynote-355, which studied the effect and safety of Pembrolizumab in combination with chemotherapy and compared it to chemotherapy monotherapy in patients with metastatic TNBC. The first study included patients from different countries as it was a multi-center study, and the second one focused only on patients who enrolled in Japan. One study was chosen from keynote-119 studies, which compared health-related quality of life for patients who were treated with pembrolizumab monotherapy or with monotherapy of chemotherapy. The last two articles which were chosen were about keynote-522. The first article about keynote-522 compared was a multicenter study enrolled in 21 countries. In this study, patients had early-stage TNBC and received neoadjuvant placebo chemotherapy or pembrolizumab chemotherapy. After the breast operation, either adjuvant pembrolizumab or placebo was received. The other study looked at Asian patients who enrolled in keynote-522. Results showed that monotherapy with pembrolizumab did not make a massive difference in overall survival compared to chemotherapy. Still, it led to better health- related quality of life for patients (Combined Positive Score (CPS) ≥ 10) treated with pembrolizumab. Results from keynote-355 showed that combination therapy with pembrolizumab and chemotherapy led to better and longer progression-free survival and overall survival in patients with CPS ≥ 10 treated with pembrolizumab. The analysis of Japanese patients showed even better progression-free survival and overall survival results than the global population. The study from keynote-522 showed that neoadjuvant pembrolizumab and chemotherapy followed by adjuvant pembrolizumab had a better effect than only neoadjuvant chemotherapy. The second keynote-522 study showed the same results as the global study and better results at event-free survival for the Asian population than the overall population. After reviewing the articles, it was found that pembrolizumab proves to be a safe and effective treatment for TNBC. To enhance understanding of the drug's effects, measures such as extending follow-up periods, conducting further studies to assess its effectiveness, and exploring new research methodologies are proposed.
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