tremelimumab and durvalumab

Regarding efficacy, the median overall survival (OS) was 18.7 months with the high-dose tremelimumab combination, 13.6 months with durvalumab monotherapy, … There are now lacking the head-to-head clinical studies comparing the efficacy between anti-PD-1 therapy and anti-PD-L1 therapy. For immediate assistance, contact Customer Service: Conference abstracts were excluded, due to the absence of raw data and the increase of heterogeneity. Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study. Similar clinical trials are underway in Italy and in 104 study locations worldwide. Introduction. The confirmed ORR and median duration of response were 58.4% and 5.2 months, respectively, in the tremelimumab + durvalumab + EP group compared with 58.0% and 5.1 months for the EP arm. You also have the option to opt-out of these cookies. The effects and safety of PD-1/PD-L1 inhibitors on head and neck cancer: a systematic review and meta-analysis. The addition of tremelimumab to durvalumab (Imfinzi) and the standard of care (SOC), platinum-based chemotherapy, did not demonstrate a statistically significant improvement in overall survival (OS) in patients with extensive-stage small cell lung cancer (ES-SCLC), missing the co-primary end point of the phase III CASPIAN trial (NCT03043872), according to high-level results from the final analysis … [39]. Cancer immunoediting: from immunosurveillance to tumor escape. (2) patients did not previously receive immunotherapy. Cohen EEW, Soulieres D, Le Tourneau C, et al. Accordingly, the meta-analyses of ORR and DCR were at moderate risk of reporting bias (Fig. Tremelimumab and Durvalumab Discussion Board › Forums › Clinical Trials › Tremelimumab and Durvalumab This topic has 19 replies, 5 voices, and was last updated 3 years, 11 months ago by marions . Forest plots of odds ratios for objective response in advanced solid tumors. [6]. Nature 2019;576:465–70. Keyword Highlighting T-cell homing specificity and plasticity: new concepts and future challenges. [54–56] However, T cell exhaustion could drive a decline in the ability of T cells to kill tumor cells. Li Z, Chen L, Rubinstein MP. We also use third-party cookies that help us analyze and understand how you use this website. This website uses cookies to improve your experience while you navigate through the website. The OS survival rates at 18 months were 32.0% in the durvalumab + EP arm, 30.7% in the tremelimumab + durvalumab + EP group, and 24.8% in the EP cohort; at 24 months, those rates were 22.2%, 23.4%, and 14.4%, respectively. Durvalumab and tremelimumab combination therapy had a good safety profile and resulted in clinical benefit in head and neck squamous cell carcinoma. cState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou, China. Durvalumab/Tremelimumab in combination of cytotoxic chemotherapy has not been tested, especially in BTC. The type of tumors was complex and different cancer types had different inflamed and tumor mutation burden backgrounds, which could directly diminish the interpretability of the meta-analysis. Future explorations are needed to further confirm the application of durvalumab plus tremelimumab. Dunn GP, Bruce AT, Ikeda H, et al. [50–52], The lack of efficacy of adding tremelimumab to durvalumab may be attributed to the mechanism of action, as tremelimumab is an IgG2 monoclonal antibody that does not cause lysis of regulatory T cells through the way of antibody-dependent cell-mediated cytotoxicity, which is observed with ipilimumab. A single 300 mg priming dose of tremelimumab in combination with durvalumab appeared safe and active among patients with advanced hepatocellular carcinoma, according to … Tumor-infiltrating lymphocytes are associated with the response to immunotherapy. The median OS for this combination was 10.4 months versus 10.5 months for EP alone (HR 0.82; 95% CI 0.68-1.00; P=0.0451). Primary efficacy endpoint is response rate. 2). [7]. In addition, open-label studies might increase publication bias even the trials were conducted in various centers. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. N Engl J Med 2018;379:2342–50. [46]. In subgroup analysis, P value did not indicate statistical significance. 2020;99:28(e21273). We found that treatment with tremelimumab plus durvalumab in the first-line and second-line setting was clinically active and safe in patients with unresectable mesothelioma. PD-1 and its ligands in tolerance and immunity. | Privacy Policy. The forest plots of odds ratios for ORR and DCR are shown in Figures 2 and 3. 2019;394(10212):1929-1939. Clin Cancer Res 2013;19:5300–9. The authors have no conflicts of interest to disclose. All enrolled studies are phase I or II clinical trials, whereas data from randomized controlled phase III studies are lacking. Supervision: Bi-Cheng Wang, Ji-Quan Fan, Quentin Liu. [5] The combination of nivolumab, a fully human anti–PD-1 inhibitor, and ipilimumab, a fully human anti–CTLA-4 inhibitor, has shown encouraging clinical benefit characterized by antitumor effects and tolerable safety profiles.[6–11]. Medicine (Baltimore) 2019;98:e18054. A random-effect model was used due to the synthesis of different cancer types. Proc Natl Acad Sci U S A 2018;115:E4041–50. Your message has been successfully sent to your colleague. observed with durvalumab and durvalumab plus tremelimumab. PD-1 is also over-expressed on intra-tumoral Treg cells and might enhance the immunosuppressive capability. According to previously published studies, PD-1 antibodies and PD-L1 antibodies showed unequal treatment effects. An intra-tumoral niche maintains and differentiates stem-like CD8 T cells. Romano E, Kusio-Kobialka M, Foukas PG, et al. APACHE: an open label, randomized, phase II study of Durvalumab (Durva), alone or in combination with. Finally, 5 clinical studies were found to meet the inclusion criteria. Eligible studies should meet all of the following criteria: We have no restrictions on language. Cancer immunotherapy comes of age. Any discrepancies were resolved by discussion. Phase II study of dual immune checkpoint blockade (ICB) with durvalumab (Durva) plus, [24]. Adv Immunol 2006;90:51–81. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. Tremelimumab will be provided for 4 cycles. Owing to the synergistic roles of the PD-1 or PD-L1 and CTLA-4 in T-cell activation, the combination of inhibitors targeting PD-1/PD-L1 and CTLA-4 signaling pathways warrants investigation. Patients in the durvalumab plus tremelimumab and chemotherapy received either 1,500 mg of durvalumab, 75mg of tremelimumab and durvalumab maintenance therapy or durvalumab and tremelimumab every 4 weeks. [11]. Hallmarks of cancer: the next generation. Safety and efficacy of durvalumab with or without, [29]. Methods: This is a single arm exploratory investigator-initiated trial planned to include 57 pts to receive mFOLFOX6 (6cycles) in combination with durvalumab (150mg/q2W) and tremelimumab (75mg/q4W). [21–26] Although combining durvalumab and tremelimumab results in clinical benefit, whether combination therapy is superior to durvalumab or tremelimumab monotherapy remains uncertain. [55]. Basic characteristics of the selected prospective and registered clinical trials. However, future studies are also needed to identify the patients that most possibly benefit from dual immune checkpoint inhibitors. Nivolumab is a PD-1 inhibitor, whereas durvalumab is a PD-L1 inhibitor. Curr Opin Immunol 2012;24:207–12. Cell 2011;144:646–74. [1,2] However, survival outcomes still need to be improved in patients with recurrent or metastatic solid tumors. Both durvalumab and tremelimumab have been tested for mesothelioma alone, but not in combination. Get new journal Tables of Contents sent right to your email inbox, http://creativecommons.org/licenses/by-nc/4.0, July 10, 2020 - Volume 99 - Issue 28 - p e21273, Durvalumab and tremelimumab combination therapy versus durvalumab or tremelimumab monotherapy for patients with solid tumors: A systematic review and meta-analysis, Articles in Google Scholar by Bi-Cheng Wang, MD, Other articles in this journal by Bi-Cheng Wang, MD, High-resolution computed tomography of the lung in patients with rheumatoid arthritis: Prevalence of interstitial lung disease involvement and determinants of abnormalities, Treatment of urinary incontinence after total hysterectomy with acupuncture: A case report, Prevalence, risk factors, and prognosis of interstitial lung disease in a large cohort of Chinese primary Sjögren syndrome patients: A case-control study, Survival benefit of neoadjuvant chemotherapy for resectable breast cancer: A meta-analysis, Sarcopenia is an Independent Predictor of Severe Postoperative Complications and Long-Term Survival After Radical Gastrectomy for Gastric Cancer: Analysis from a Large-Scale Cohort. After 6 cycles of chemotherapy, patients are treated with durvalumab untils progression. Patients with advanced or recurrent disease lack these niches, suggesting that niche breakdown in tumor tissues may be a key factor of immune resistance or escape.[57]. Trends Immunol 2006;27:235–43. Lee JJ, Yothers G, George TJ, et al. Real-time immune cell interactions in target tissue during autoimmune-induced damage and graft tolerance. [13] Another open-label, phase III trial displayed that nivolumab plus ipilimumab prolong median OS compared to chemotherapy in advanced NSCLC patients regardless of the status of PD-L1 (17.1 versus 13.9 months), and suggested combining nivolumab and ipilimumab as a first-line treatment for advanced NSCLC.[6]. J Clin Oncol 2019;37:992–1000. Mesothelioma patients treated with durvalumab plus tremelimumab had the longest median survival time (median PFS: 5.7 months, 95% confidence interval [CI] 1.7–9.7; median OS: 16.6 months, 95% CI 13.1–20.1). To evaluate the efficacy and safety of durvalumab in combination with tremelimumab compared with either drug alone. Durvalumab plus tremelimumab showed similar risks of any grade treatment-related adverse events with durvalumab monotherapy (RR 1.01, 95% CI 0.69–1.49, P = .95) and tremelimumab monotherapy (RR 1.02, 95% CI 0.79–1.32, P = .87) (Fig. N Engl J Med 2016;375:1856–67. T cell motility is increased by CTLA-4 via limiting contact time between T cells and antigen-presenting cells (APCs). J Immunol 2015;194:950–9. © 2020 Medicom Medical Publishers. Stewart R, Morrow M, Hammond SA, et al. This website uses cookies. Exp Hematol Oncol 2013;2:33. The randomized clinical studies had reported all their pre-defined results. Safety events were consistent with the known adverse events (AEs) associated with the medicines. The item(s) has been successfully added to ", This article has been saved into your User Account, in the Favorites area, under the new folder. 30 mins. [13–19] Further, adding tremelimumab, a high affinity human IgG2 monoclonal antibody of CTLA-4,[20] to durvalumab therapy has also been under detection in different cancers. The first author, year of publication, register number, study design, county, cancer type, number of patients, mean age, lines of prior therapy, dosing schedule, objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and treatment-related adverse events data reporting in the articles and supplementary materials were collected from each eligible study. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Data from randomized studies (ORR and DCR) was assessed by odds ratio (OR) and 95% confidence interval (CI). Background: The combination of durvalumab (D), (anti- PD-L1) and tremelimumab (T), (anti-CTLA-4), was evaluated to determine activity in specific sarcoma subtypes (NCT02815995). Savas P, Virassamy B, Ye C, et al. [28]. Efficacy and safety of combination immunotherapy for malignant solid tumors: a systematic review and meta-analysis. However, a lower risk of any grade treatment-related adverse events was seen in HNSCC (RR 0.92). The analysis of ORR and DCR comprised 3 types of cancers that might not fully represent the efficacy of combination therapy in solid tumors. Open Med 2009;3:e123–30. In comparison with patients in monotherapy groups, patients in the durvalumab and tremelimumab combination therapy group showed no significant increases in grade ≥ 3 treatment-related adverse events (durvalumab and tremelimumab versus durvalumab: RR 1.64, 95% CI 0.86–3.13, P = .14; durvalumab and tremelimumab versus tremelimumab: RR 0.87, 95% CI 0.46–1.65, P = .67) (Fig. A recent study indicated that T cells were stored in dense antigen-presenting-cell niches within the tumor microenvironment, but tumors that failed to form these immune niches were not extensively infiltrated by T cells. Jansen CS, Prokhnevska N, Master VA, et al. J Exp Med 2014;211:441–56. The electronic databases PubMed, Web of Science, EMBASE and Cochrane Library were systemically searched for all relevant records until Nov 26, 2019. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. A pilot study of durvalumab and tremelimumab and immunogenomic dynamics in metastatic breast cancer. The median OS was 16.3 months (95% CI, 12.2-20.8) with durvalumab vs 12.9 months (95% CI, 10.5-15.0) with chemotherapy (hazard ratio [HR], 0.76; 97.54% CI, 0.56-1.02; P = .04 ( Figure 2 A). For pooled analyses of the ORR and DCR in randomized studies, the Cochrane Risk of Bias Tool was applied to evaluate the risk of bias. Phase 2 study of, [22]. AEs leading to treatment discontinuation occurred in 21.4% of patients in the tremelimumab + durvalumab + EP arm, 10.2% in the durvalumab + EP group, and 9.4% in the EP cohort. Lippincott Journals Subscribers, use your username or email along with your password to log in. [43]. Drake CG, Jaffee E, Pardoll DM. Registered users can save articles, searches, and manage email alerts. Data for durvalumab alone showed activity consistent with that of other single-agent immune checkpoint inhibitors in this setting, including in the intention-to-treat population. Morse MA, Overman MJ, Hartman L, et al. Francisco LM, Sage PT, Sharpe AH. Ferris RL, Blumenschein G Jr, Fayette J, et al. In the durvalumab plus chemotherapy group, patients received a dose of 1,500 mg with four cycles of chemotherapy every 3 weeks. Oncologist 2019;24:1453–61. N Engl J Med 2015;372:2006–17. 800-638-3030 (within USA), 301-223-2300 (international). Immunol Rev 2010;236:219–42. [47], Consequently, dual inhibition of CTLA-4 and PD-1/PD-L1 might be a reasonable and potentially synergistic therapeutic modality advanced cancer patient. The work cannot be used commercially without permission from the journal. In the current presentation, after a median follow-up of 25.1 months, the median OS was 12.9 months among patients who received durvalumab + EP compared with 10.5 months for those who received EP alone (HR 0.75; 95% CI 0.62-0.91; P=0.0032), fully supporting the initial report. Patients received durvalumab (1500 mg every 4 weeks) plus tremelimumab (75 mg every 4 weeks) combination therapy for 4 cycles followed by durvalumab therapy (1500 mg every 4 weeks) or durvalumab monotherapy (1500 mg every 4 weeks) for up to 12 months or until the onset of progressive disease or unacceptable toxic effects. Topalian SL, Drake CG, Pardoll DM. [12]. Writing – original draft: Bi-Cheng Wang, Ji-Quan Fan, Quentin Liu. O’Reilly EM, Oh DY, Dhani N, et al. However, the study’s third arm testing dual checkpoint blockade with tremelimumab + durvalumab + EP did not meet the prespecified threshold for statistical significance (P≤0.0418). Patients treated with a single, priming dose of tremelimumab 300mg added to durvalumab every four weeks (T300+D regimen) achieved a median overall survival (OS) of 18.7 months in a … [21]. Selumetinib may stop the growth of tumor … A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application. Siu LL, Even C, Mesia R, et al. Nat Med 2018;24:986–93. [5]. Please try after some time. Mechanisms of immune evasion by tumors. Lancet Oncol 2016;17:883–95. Therefore, ethical approval was not necessary. Nat Immunol 2002;3:991–8. [40–42] In the peripheral tissues, PD-1 limits the activation of T-cell through suppressing the induction of cytokines and the expression of anti-apoptotic proteins. Lancet Oncol 2018;19:521–36. In subgroup analyses, durvalumab plus tremelimumab was shown to have a higher rate of disease control in HNSCC compared to tremelimumab alone (OR 9.41, 95% CI 1.22–72.41, P = .03). Durvalumab and tremelimumab demonstrated clinical benefit with a prolonged survival and manageable toxicity profile in patients with recurrent or metastatic PSC. Kelly RJ, Lee J, Bang YJ, et al. Conceptualization: Bi-Cheng Wang, Peng-Cheng Li, Guo-He Lin. The combination of tremelimumab and durvalumab appeared active, with a good safety profile in patients with mesothelioma, warranting further exploration. For more information, please refer to our Privacy Policy. The blockage of CTLA-4 and PD-1 exerts critical anti-tumor effects. You may search for similar articles that contain these same keywords or you may 6). The action mechanism of CTLA-4 remains less clear. Fife BT, Pauken KE, Eagar TN, et al. J Exp Med 2000;192:1027–34. Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients. [20]. Safety and antitumour activity of durvalumab plus. We report final results of the clinical efficacy, safety and correlatives. Presented by Prof. Luis Paz-Ares (Hospital 12 de Octubre, Madrid, Spain), this was the first report of the third study arm of CASPIAN, in which the investigational CTLA-4 inhibitor tremelimumab was added to PD-L1 checkpoint inhibitor durvalumab on top of standard of care chemotherapy [1]. The basic characteristics of the 5 eligible studies are list in Table 1. The treatment-related analyses were assessed by risk ratio (RR) and 95% CI. [36]. Any cookies that may not be particularly necessary for the website to function and is used specifically to collect user personal data via analytics, ads, other embedded contents are termed as non-necessary cookies. [9]. Durvalumab has no prior approvals to treat HCC in any country. Eroglu Z, Zaretsky JM, Hu-Lieskovan S, et al. But opting out of some of these cookies may have an effect on your browsing experience. Paz-Ares LG, et al. While compared with tremelimumab monotherapy, combination therapy showed a higher risk of any grade treatment-related adverse events in HNSCC (RR 1.05) but a lower risk in GGA (RR 0.68). Cancer Immunol Res 2015;3:1052–62. Although the median OS of patients with PDA, HNSCC, and GGA ranged from 3.1 to 10.6 months, the median PFS time was no more than 2 months. Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal. (A) Durvalumab plus, Forest plots of odds ratios for disease control in advanced solid tumors. Secondary analyses suggested that tremelimumab resulted in increased antitumour activity, albeit with greater toxicity, when given in combination with durvalumab. Purpose: This randomized, multicenter, open-label, phase Ib/II study assessed durvalumab and tremelimumab in combination or as monotherapy for chemotherapy-refractory gastric cancer or gastroesophageal junction (GEJ) cancer. High response rate to PD-1 blockade in desmoplastic melanomas. Durvalumab 1500 mg plus tremelimumab 75 mg via IV infusion Q4W, starting on Week 0, for up to a maximum of 4 doses/cycles followed by durvalumab monotherapy 1500 mg via IV infusion Q4W, starting 4 weeks after the last infusion of the combination, until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria met (Fig. [49] However, such benefits were not observed when solid tumor patients were treated with durvalumab and tremelimumab in our study. Tremelimumab is a human monoclonal antibody that is being tested in combination with durvalumab in non—small cell lung cancer (NSCLC), small cell lung cancer (SCLC), bladder cancer, head and neck cancer, and liver cancer. AstraZeneca’s Imfinzi (durvalumab) and tremelimumab, an anti-CTLA4 antibody and potential new medicine, have both been granted Orphan Drug Designation (ODD) in the US for the treatment of hepatocellular carcinoma (HCC), the most common type of liver cancer. B-CW and P-CL independently conducted the selection process. Keir ME, Butte MJ, Freeman GJ, et al. Wei Y, Du Q, Jiang X, et al. Data is temporarily unavailable. Durvalumab with or without, [30]. The combination of durvalumab and tremelimumab results in clinical benefit, with a tolerable safety profile in patients with solid tumors. The primary endpoint was OS and a 2-sided P < 0.10 was considered statistically significant. (A) Each risk of bias item presented as percentages across all included randomized clinical studies; (B) Each risk of bias item for each included randomized clinical study. [50]. [14]. Eur J Cancer 2019;109:154–61. Further, 150 records were excluded after review of the titles and abstracts. [48] A phase III clinical study, Checkmate-067, showed a median PFS of 11.5 months in patients treated with nivolumab and ipilimumab combination therapy, compared with 2.9 and 6.9 months in patients treated with ipilimumab or nivolumab monotherapy, respectively. Study design, data extraction, and data analysis: BW, GL, and PL; manuscript writing and edition: BW, JF and QL. Ann Oncol 2019;30:1279–88. Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study. Ribas A, Camacho LH, Lopez-Berestein G, et al. Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. Durvalumab and tremelimumab combination therapy appeared active for the treatment of HNSCC. [37]. SBRT to 2-5 metastases will be administered between cycles 2 and 3 of immunotherapy. One hundred seventy-three records underwent full-text assessment. 5). Necchi A, Mariani L, Raggi D, et al. [33–35] Nowadays, immune checkpoint inhibitors have revolutionized the treatment of patients with solid tumors. your express consent. Funding acquisition: Bi-Cheng Wang, Guo-He Lin. http://creativecommons.org/licenses/by-nc/4.0. Featured video: Durvalumab ± tremelimumab + platinum-etoposide in first-line extensive-stage SCLC (ES-SCLC): Updated Results from the phase III CASPIAN study. [33]. Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis. The confirmed ORR and median duration of response were 58.4% and 5.2 months, respectively, in the tremelimumab + durvalumab + EP group compared with 58.0% and 5.1 months for the EP arm. (4) studies were prospective and registered clinical trials. [30] Nevertheless, durvalumab plus tremelimumab showed similar efficacy to durvalumab monotherapy in recurrent or metastatic head and neck squamous cell carcinoma and pancreatic ductal adenocarcinoma. modify the keyword list to augment your search. However, higher effects were not observed in the combination therapy group. Calabro L, Morra A, Giannarelli D, et al. Eur J Cancer 2019;116:137–47. Please enable scripts and reload this page. Three studies comprised durvalumab monotherapy and 2 studies contained tremelimumab monotherapy. Research Article: Systematic Review and Meta-Analysis. The Authors. Safety and efficacy of durvalumab in patients with head and neck squamous cell carcinoma: results from a phase I/II expansion cohort. [12] Remarkable clinical activity and manageable safety of durvalumab were reported in various solid tumors, including melanoma, lung cancer, head and neck cancer, breast cancer, and urothelial carcinoma. Accordingly, we conducted this systematic review and meta-analysis to assess the efficacy and safety of durvalumab plus tremelimumab combination therapy versus durvalumab or tremelimumab monotherapy in solid tumors. [1]. Figure 1 displays the selection process. [38] Another study has demonstrated that anti-CTLA-4 treatment increases the action of Treg and CD4 T cells but decreases the action of CD8 T cells. [35]. Some error has occurred while processing your request. [4]. All rights reserved. [3,4] PD-1 inhibitors and cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors are immune checkpoint antibodies with distinct but complementary mechanisms of action. [8]. Your account has been temporarily locked due to incorrect sign in attempts and will be automatically unlocked in All data generated or analyzed during this study are included in this published article [and its supplementary information files]. [34]. ASCO Virtual Meeting, 29-31 May 2020, Abstract 9002. CASPIAN randomised 805 patients to 3 treatment arms: durvalumab + tremelimumab + etoposide cisplatin/carboplatin (EP; n=268), EP alone (n=269), or durvalumab + EP (n=268). Cancer immunotherapy: are we there yet? Durvalumab plus tremelimumab was superior to tremelimumab monotherapy in improving disease control rate in head and neck squamous cell carcinoma. Higher serum levels of eicosapentaenoic acid correlate with reduced CV events, Evinacumab significantly reduces LDL-C in homozygous FH patients, COVID-19 and Cancer Consortium Registry: initial results, Oncology hospital-at-home model reduces hospitalizations, emergency department visits, and costs, Nurse-led telephone triage system reduces hospitalizations, helps patients manage symptoms at home, Adjuvant pembrolizumab: durable RFS for stage III melanoma, Pembrolizumab plus low-dose ipilimumab well tolerated after progression on PD1 antibody therapy, Toripalimab plus axitinib effective in metastatic mucosal melanoma, Advanced breast cancer: locoregional therapy does not improve OS, T-DM1 does not improve safety or efficacy in HER-2 positive early breast cancer; favorable iDFS reported, Maintenance olaparib improves OS in relapsed ovarian cancer with BRCA1/2 mutation, Combination pembrolizumab/chemo improves PFS in metastatic TNBC, Effect of veliparib with or without cisplatin in breast cancer: results of SWOG S1416, PHOEBE, a phase 3 trial comparing pyrotinib and lapatinib in HER2-positive metastatic breast cancer, BYLieve demonstrates efficacy of PIK3CA-directed treatment post CDK4/6-ihibition, Strategies emerge for chemotherapy de-escalation in HER2-positive breast cancer, Carfilzomib: no PFS benefit for multiple myeloma, ES-SCLC: tremelimumab + durvalumab + chemotherapy misses endpoint, Adjuvant osimertinib in NSCLC: practice changing ADAURA trial, Second-line gemcitabine plus ramucirumab significantly improves overall survival, Tiragolumab and atezolizumab: ORR in NSCLC, MET-amplified advanced NSCLC responds well to MET inhibitor capmatinib, Urothelial cancer: avelumab works as maintenance therapy, ARAMIS final OS and nmCRPC safety outcomes, Final survival results from phase 3 SPARTAN trial, Novel drug for kidney cancers/VHL patients, Primary analysis from IMvigor010, adjuvant atezolizumab in high risk muscle-invasive urothelial carcinoma, First randomised trial of Lu-PSMA in mCRPC progressing after docetaxel, HER2-expressing metastatic colorectal cancer: trastuzumab deruxtecan, Pembrolizumab as first-line in MSI-H mCRC, REGOMUNE: a phase 2 study combining regorafenib and avelumab, Cardiotoxicity: consider switching to S-1, Perioperative chemotherapy for resectable pancreatic ductal adenocarcinoma, Real-world data of sequential sorafenib followed by regorafenib in unresectable HCC, Sustained improvements in quality of life with larotrectinib, Promising first immunotherapy trial in placental trophoblastic tumours, Precision medicine for poor-prognosis paediatric patients. Durvalumab and tremelimumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Segal NH, Ou SI, Balmanoukian A, et al. Overall, 5 studies were eligible for systematic review, 3 of which were further meta-analyzed. Treatment-related deaths were 12 in the tremelimumab + durvalumab + EP arm, 6 in the durvalumab + EP arm, and 2 in the EP arm. In addition, PD-L1 is expressed in tumor-infiltrating immune cells. [51]. Methods Eligible pts had ≥2 prior systemic treatments (1 platinum-based CT), WHO PS 0/1, no prior PDx and were EGFR/ALK WT. Patients will receive durvalumab (1500 mg IV every 4 weeks (Q4W)) and tremelimumab (75 mg IV Q4W for a total of 4 doses) until progression, unacceptable toxicity or patient withdrawal. Median progression-free survival and overall survival in the eligible studies. Macrophages impede CD8 T cells from reaching tumor cells and limit the efficacy of anti-PD-1 treatment. In a randomized, double-blind, phase II study, the response rates of melanoma patients were significantly higher in nivolumab plus ipilimumab group (61%) than in ipilimumab group (11%) (P < .001). Efficacy and safety of durvalumab in locally advanced or metastatic urothelial carcinoma: updated results from a phase 1/2 open-label study. Nivolumab plus ipilimumab in non-small-cell lung cancer. [54]. DUTRENEO Trial: A phase II randomized trial of DUrvalumab and, [25]. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. A random-effects model was applied in the analyses owing to the small size of enrolled studies. One study was phase 1b clinical trial, 1 was phase 1b/2 clinical trial, and three were phase 2 clinical trials. Lancet 2019;393:156–67. ∗Correspondence: Bi-Cheng Wang, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China (e-mail: [email protected]).

Menentukan Isi Dari Definisi Umum, Journal Of Agricultural Sciences Belgrade, Zahlt Moderna Dividende, Dr Kraus Diabetologe Augsburg, Adidas Trikotsatz 2019,