Objective: Over the last several years, immunotherapy has become one of the most promising therapeutic options for cancer. This study aims to summarize the updates on cancer immunotherapy focusing on immune checkpoint inhibitors, such as programmed cell death-1 (PD-1), programmed death-ligand 1 (PD-...
Objective: Over the last several years, immunotherapy has become one of the most promising therapeutic options for cancer. This study aims to summarize the updates on cancer immunotherapy focusing on immune checkpoint inhibitors, such as programmed cell death-1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, which have received attention as new anticancer therapeutic agents. Methods: A literature survey was carried out on PubMed to identify high-impact papers on cancer immunotherapy from 2010. The most recent data on clinical efficacy and safety have been included highlighting the response characteristics to recently approved immunotherapeutic agents. Results: In various cancers, immune checkpoints are a means for cancer cells to evade the immune system. Furthermore, CTLA-4 and PD-L1 can be overexpressed, allowing malignant cells to evade T-cells. Numerous clinical trials have been performed to seek appropriate indication of these products in various cancer types. Among them, the most conspicuous types are melanoma, non-small-cell lung cancer, and head and neck cancer. The approval of ipilimumab by Food and Drug Administration (FDA) commenced a new era of cancer immunotherapy. This was followed by the approval of nivolumab and pembrolizumab. Currently, combination therapies are being investigated for various cancer types. Conclusion: In this study, we reviewed recently reported scientific and clinical evidence for currently approved immune checkpoint inhibitors. Although these novel checkpoint inhibitors are ever evolving for cancer therapies, there exist limitations that need to be overcome, indicating the necessity for further studies aiming to improve their efficacy, toxicity, and cost.
Objective: Over the last several years, immunotherapy has become one of the most promising therapeutic options for cancer. This study aims to summarize the updates on cancer immunotherapy focusing on immune checkpoint inhibitors, such as programmed cell death-1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, which have received attention as new anticancer therapeutic agents. Methods: A literature survey was carried out on PubMed to identify high-impact papers on cancer immunotherapy from 2010. The most recent data on clinical efficacy and safety have been included highlighting the response characteristics to recently approved immunotherapeutic agents. Results: In various cancers, immune checkpoints are a means for cancer cells to evade the immune system. Furthermore, CTLA-4 and PD-L1 can be overexpressed, allowing malignant cells to evade T-cells. Numerous clinical trials have been performed to seek appropriate indication of these products in various cancer types. Among them, the most conspicuous types are melanoma, non-small-cell lung cancer, and head and neck cancer. The approval of ipilimumab by Food and Drug Administration (FDA) commenced a new era of cancer immunotherapy. This was followed by the approval of nivolumab and pembrolizumab. Currently, combination therapies are being investigated for various cancer types. Conclusion: In this study, we reviewed recently reported scientific and clinical evidence for currently approved immune checkpoint inhibitors. Although these novel checkpoint inhibitors are ever evolving for cancer therapies, there exist limitations that need to be overcome, indicating the necessity for further studies aiming to improve their efficacy, toxicity, and cost.
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제안 방법
These checkpoint inhibitors not only have yielded new therapeutic options for patients with cancer, but are regarded as the fourth cornerstone of anticancer treatment attracting many clinicians and pharmacists. This article summarizes the mechanism of action, differences, and similarities of checkpoint inhibitors, therapeutic uses, and predictive biomarkers of response, as well as their limitations in clinical application.
대상 데이터
IMvigor 210 is an open-label, multicenter, two-cohort phase 2 study that has evaluated the safety and efficacy of atezolizumab in patients with locally advanced or metastatic urothelial carcinoma, regardless of PD-L1 expression. Between May 13, 2014, and November 19, 2014, 486 patients were screened, with 315 of them being enrolled into the study. Of these patients, 310 have received atezolizumab treatment (the remaining 5 patients have not met the eligibility criteria and have not been treated with the examind drug).
The clinical study CheckMate-066 has been conducted with previously untreated patients with BRAF wild-type unresectable stage III and IV melanoma. The trial has enrolled 418 patients who were randomized to receive either nivolumab 3 mg/kg every 2 weeks or dacarbazine 1000 mg/m2 every 3 weeks. A primary endpoint of overall survival and secondary endpoints of progression-free survival and objective response rate have been assessed.
성능/효과
5) Keynote-002 is a randomized phase 2 trial of 540 patients with melanoma that progressed on ipilimumab, and if BRAFV600mutant- positive, previously treated with a BRAF or MEK inhibitor or both; those patients have few treatment options. Based on 410 total progression-free survival events, the study has met the pre-specified criteria to show significant improvement in progression-free survival, with hazard ratios of 1.57 (95% CI, 0.45 to 1.73) for pembrolizumab 2 mg/kg and 1.5 (95%CI, 1.39 to1.64) for pembrolizumab10 mg/kg compared with chemotherapy. The most common treatment-related grade 3–4 adverse event that has been observed in the pembrolizumab groups was fatigue (2 [1%] out of 178 patients in the 2 mg/kg group and 1 [<1%] out of 179 patients in the 10 mg/kg group, compared with 8[5%] out of 171 in the chemotherapy group).
0001). The 1 and 2 year survival rates following ipilimumab monotherapy (46% and 24%, respectively), were nearly double of those following gp100 vaccine (25% and 14%, respectively). Immune-related adverse events (irAEs) occurred in approximately 60% of patients receiving ipilimumab compared with about 32% of those receiving only gp100.
The median progression-free survival was 11.5 months (95% confidence interval CI, 8.9 to 16.7) with nivolumab plus ipilimumab, compared with 2.9 months (95% CI, 2.8 to 3.4) with ipilimumab (HR for death or disease progression, 0.42;99.5% CI, 0.31 to 0.57; P<0.001), and 6.9 months (95% CI, 4.3 to 9.5) with nivolumab (HR, 0.57; 99.5% CI, 0.43 to 0.76; P < 0.001).
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