Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Schwere Nebenwirkungen (Grad 3 oder 4) traten bei 250 Patienten (46%) bzw. S8). Hierarchical secondary end points were progression-free survival, according to blinded independent central review; overall survival with nivolumab plus chemotherapy, as compared with chemotherapy alone, in patients with a PD-L1 expression level of less than 1%; and overall survival with nivolumab monotherapy, as compared with chemotherapy, in patients with a PD-L1 expression level of 50% or more. 0,0001). S9 and Table S9). Datenbank mit Informationen, Adressen und Präparaten der Pharma-Hersteller. Into your bloodstream . Ipilimumab, a fully human, IgG1 monoclonal antibody blocking cytotoxic T-lymphocyteassociated antigen 4 (CTLA-4), improved overall survival in patients with advanced melanoma.3,4 Nivolumab, a fully human IgG4 antibody blocking the p… Über 110.000 Arzneimittel und Medizinprodukte mit Anwendungs- und Fachinformationen. Es ist nicht bekannt, ob der Wirkstoff in die Muttermilch übergeht. We also evaluated the benefit of nivolumab plus ipilimumab, as compared with nivolumab plus chemotherapy, in patients with a PD-L1 expression level of less than 1% (Fig. 28. Nivolumab ist ein humaner Immunglobulin G4 (IgG4) monoklonaler Antikörper, der zur Therapie von fortgeschrittenen Melanomen, nicht-kleinzelligem Lungenkarzinom, Nierenzellkarzinom, klassischem Hodgkin-Lymphom, Plattenepithelkarzinom des Kopf-Hals-Bereiches sowie des Urothelkarzinoms zugelassen ist. Nivolumab hatte jedoch keinen Effekt auf die CL von Ipilimumab. Ipilimumab is an anti-CTLA-4 drug, which is an antibody that helps strengthen the immune system by promoting the function and growth of T-cells. Characteristics of the Patients at Baseline.*. PLoS Comput Biol 2018;14(2):e1005965-e1005965. ¶ The number of mutations (mut) was determined with the use of the FoundationOne CDx assay. Der PD1-Rezeptor ist als negativer Regulator der T-Zellaktivität an der Kontrolle der T-Zellreaktionen beteiligt. Adverse events were assessed by the investigator and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Also shown are the 1-year and 2-year rates of survival in the two groups. Pembrolizumab plus chemotherapy in metastatic non–small-cell lung cancer. Among all the trial patients, regardless of the PD-L1 expression level, the median duration and rate of overall survival were higher among the patients who received nivolumab plus ipilimumab than among those who received chemotherapy, with a duration of 17.1 months (95% CI, 15.2 to 19.9) and 13.9 months (95% CI, 12.2 to 15.1), respectively, and a rate of overall survival of 40.1% and 29.7%, respectively, at 2 years (Figure 2B); the overall survival benefit was consistent across most subgroups (Fig. 11. Address reprint requests to Dr. Hellmann at the Thoracic Oncology Service, Department of Medicine, Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, 885 2nd Ave., New York, NY 10017, or at [email protected]. First-line treatment with nivolumab plus ipilimumab resulted in a longer duration of overall survival than did chemotherapy in patients with NSCLC, independent of the PD-L1 expression level. 2. Overall Survival in Patients with a Tumor PD-L1 Expression Level of Less Than 1% and in All the Patients. The median duration of response was 23.2 months (95% CI, 15.2 to 32.2) with nivolumab plus ipilimumab and 6.2 months (95% CI, 5.6 to 7.4) with chemotherapy. § The status of PD-L1 expression was determined with the use of the PD-L1 IHC 28–8 pharmDx assay (Dako). The frequency of grade 3 or 4 adverse events that were determined by the investigator to be related to the trial treatment was similar in the group that received nivolumab plus ipilimumab and in the chemotherapy group (32.8% vs. 36.0%). Whitehouse Station, NJ: Merck, June 2019 (package insert) (https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf). Die am häufigsten aufgetretenen Nebenwirkungen bei der Kombinationstherapie mit Ipilimumab waren: Hautausschlag, Fatigue, Diarrhöe, Pruritus, Übelkeit, Pyrexie, verminderter Appetit, Hypothyreose, Kolitis, Erbrechen, Arthralgie, Bauchschmerzen, Kopfschmerzen und Dyspnoe. From the Memorial Sloan Kettering Cancer Center, New York (M.D.H. Among the patients with a PD-L1 expression level of less than 1%, fewer grade 3 or 4 treatment-related adverse events or serious adverse events were reported with nivolumab plus ipilimumab (27.0% with adverse events and 16.2% with serious adverse events) than with nivolumab plus chemotherapy (55.8% and 19.2%, respectively). Although the relative benefit of nivolumab plus ipilimumab, as compared with chemotherapy, was numerically greater in patients with a PD-L1 expression level of less than 1% than in those with a PD-L1 expression level of 1% or more, this result was mostly due to variations between the PD-L1 subgroups in both the median duration of survival and in survival rates in the chemotherapy group. In an early-phase study involving patients with advanced non–small-cell lung cancer (NSCLC), the response rate was better with nivolumab plus ipilimumab than with nivolumab monotherapy, particularly among patients with tumors that expressed programmed death ligand 1 (PD-L1). Datenbanken für Ärzte, Nivolumab hatte jedoch keinen Effekt auf die CL von Ipilimumab. The most effective and engaging way for clinicians to learn, improve their practice, and prepare for board exams. 24. In an early-phase study involving patients with advanced non–small-cell lung cancer (NSCLC), the response rate was better with nivolumab plus ipilimumab than with nivolumab monotherapy, particularly among patients with tumors that expressed programmed death ligand 1 (PD-L1). La combinazione di due molecole immuno-oncologiche, nivolumab e ipilimumab, riduce il rischio di progressione della malattia del 20%, di morte del 13% e … Ergebnisse wurden in einem Peer-Review-Journal publiziert [3]. . Nat Genet 2019;51:202-206. An independent data and safety monitoring committee provided oversight of efficacy and safety. Daher muss unter Abwägung des Nutzens des Stillens für das Kind und des Nutzens der Behandlung für die Mutter eine Entscheidung darüber getroffen werden, ob das Stillen oder die Behandlung mit Nivolumab unterbrochen werden soll. Deaths in the chemotherapy group were from sepsis (in 2 patients) and from febrile neutropenia with sepsis, multiple brain infarctions, interstitial lung disease, and thrombocytopenia (in 1 patient each). 02.12.2020 - CheckMate 238-Studie: Im Vergleich zu Ipilimumab profitieren Patienten mit reseziertem Melanom im Stadium IIIB-C oder IV langfristig von Nivolumab. Die Anwendung von Nivolumab in der Schwangerschaft wird nicht empfohlen, es sei denn, der klinische Nutzen überwiegt das potentielle Risiko. Nivolumab bindet an den Rezeptor PD-1 auf T-Lymphozyten und verhindert so dessen abwehrhemmende Wirkung. Kowanetz M, Zou W, Shames DS, et al. Treatment-related deaths occurred in 8 patients who received nivolumab plus ipilimumab and in 6 patients who received chemotherapy (Table 2). 10. Beides führt dazu, dass die Immunzellen sich stärker vermehren und aktiver werden, sodass sie die Tumorzellen energischer bekämpfen können. Ipilimumab was no longer dominated by nivolumab when the total drug cost of ipilimumab (4 doses) decreased to approximately $88,000. We planned to enroll 1200 patients for randomization into the three treatment groups in Part 1a. Gelbe Liste Online ist ein Online-Dienst der The results suggest that the superior efficacy of nivolumab plus ipilimumab over sunitinib was maintained in intermediate-risk or poor-risk and intention-to-treat patients with extended follow-up, and show the long-term benefits of nivolumab plus ipilimumab in patients with previously untreated advanced renal cell carcinoma across all risk categories. Studies of single-agent immunotherapy regimens have shown minimal benefit. Clonal replacement of tumor-specific T cells following PD-1 blockade. 15. In Part 1a, patients were randomly assigned in a 1:1:1 ratio to receive nivolumab (at a dose of 3 mg per kilogram of body weight every 2 weeks) plus ipilimumab (at a dose of 1 mg per kilogram every 6 weeks), nivolumab monotherapy (240 mg every 2 weeks), or platinum-doublet chemotherapy every 3 weeks for up to four cycles. Foundation Medicine. 14. 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. Also shown are the 1-year and 2-year rates of survival in the two groups. We further evaluated nivolumab plus ipilimumab, as compared with chemotherapy, in a prespecified descriptive analysis of patients with a PD-L1 expression level of less than 1% and in all the trial patients. Chicago – Eine Erstlinientherapie mit Nivolumab in Monotherapie oder in Kombination mit Ipilimumab ist bei Patienten mit metastasiertem Melanom signifikant wirksamer als eine Monotherapie mit Ipilimumab. We used a nonparametric log-rank test to assess the primary and secondary hierarchical end points and a stratified Cox proportional-hazards model, with the treatment group as a single covariate, to calculate hazard ratios for death with associated two-sided confidence intervals (which were 97.72% confidence intervals for end points tested in the statistical hierarchy). Nahrungsergänzungsmitteln, Verbandmitteln und Kosmetika. We determined the PD-L1 expression level13 and tumor mutational burden11,14-16 as described previously. Here, we compared the efficacy and cost … The tube stays in place throughout the course of treatment. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Find What Is A Dove and Related Articles. Die Auswirkung von Nivolumab auf die männliche oder weibliche Fertilität ist unbekannt. In this subgroup, 3 treatment-related deaths occurred in the group that received nivolumab plus ipilimumab and 4 in the group that received nivolumab plus chemotherapy. Vor Beginn der Nivolumab-Behandlung sollte die Einnahme oder Injektion von Glukokortikoiden und anderen, das Immunsystem unterdrückenden Wirkstoffen vermieden werden. Studien zur Untersuchung der Fertilität wurden nicht durchgeführt. PATIENTS AND METHODS We conducted a phase II study of nivolumab with ipilimumab in patients with … The median duration of overall survival was 15.2 months (95% CI, 12.3 to 19.8) with nivolumab plus chemotherapy and 12.2 months (95% CI, 9.2 to 14.3) with chemotherapy alone. 30.11.2020 - Bei OPDIVO 10 mg/ml Konzentrat zur Herstellung einer Infusionslösung wurden die Indikationen erweitert. Zum Vergleich von Nivolumab versus Dacarbazin ist die Studie CA209-066 geeignet. Findings In this economic evaluation using a microsimulation model, pembrolizumab-axitinib provided incremental benefit over nivolumab-ipilimumab by a measure of quality-adjusted life-years … If the proportional assumption was not met, hazard ratios were still reported to provide a conventional estimate of overall average effect and supplemented by median and landmark estimates. Durch ein malignes Melanom entstandene Metastasen werden bei mir (nach 10 x Kopfbestrahlung) seit Kurzem mit Nivolumab/Ipilimumab behandelt. Sade-Feldman M, Yizhak K, Bjorgaard SL, et al. Among the 391 patients who had a PD-L1 expression level of 1% or more who were treated with nivolumab monotherapy, grade 3 or 4 treatment-related adverse events occurred in 76 patients (19.4%), and treatment-related adverse events of any grade resulted in discontinuation in 48 patients (12.3%). The design of this trial was informed by phase 1 and 2 single-group studies of nivolumab plus ipilimumab that showed increased response rates in patients with PD-L1–expressing tumors or a high tumor mutational burden in patients with NSCLC.10,23 However, in this large, randomized study, the survival benefit with nivolumab plus ipilimumab over chemotherapy was ultimately similar in the two main PD-L1 subgroups on the basis of a cutoff of 1% of tumor cells. Mok TSK, Wu YL, Kudaba I, et al. Distinct immune cell populations define response to anti-PD-1 monotherapy and anti-PD-1/anti-CTLA-4 combined therapy. Evidence-based recommendations on nivolumab (Opdivo) with ipilimumab (Yervoy) for untreated advanced renal cell carcinoma that is intermediate- or poor-risk in 3.3 People with untreated advanced renal cell carcinoma could be offered 1 of 4 oral tyrosine kinase inhibitors, as recommended in NICE's technology appraisal guidance on cabozantinib, pazopanib, sunitinib or tivozanib. Adverse events leading to the discontinuation of ipilimumab earlier than the discontinuation of nivolumab occurred in 18 patients (3.1%). 17. 335 Patienten (63%) auf. Patients who received immunotherapy regimens could continue to receive treatment beyond disease progression if they met prespecified criteria, as described in the Methods section in the Supplementary Appendix. Nivolumab with ipilimumab OS probability: +/– 10% Nivolumab with ipilimumab PFS utility: 0.738-0.902 Pembrolizumab with axitinib PFS utility: 0.698-0.853 Mean patient weight, kg: 49 … Cancer researchers are developing more effective ways to treat advanced melanoma, including using some drugs in combination. Nivolumab ist bei erwachsenen Patienten zur Behandlung folgender Tumorarten indiziert: Nivolumab ist ein humaner Immunoglobulin-G4-(IgG4) monoklonaler Antikörper, der an den Programmierten Zelltod 1-(PD-1)-Rezeptor bindet und die Interaktion des Rezeptors mit seinen  Liganden PD-L1 und PD-L2 verhindert. Part 1 of the trial has two independent primary end points. The authorized source of trusted medical research and education for the Chinese-language medical community. N Engl J Med 2018;378:2078-2092. The rate of overall survival was significantly higher among the patients who received nivolumab plus ipilimumab than among those who received chemotherapy, but the proportional-hazards assumption was not met. — all in France; Centre Hospitalier Universitaire Vaudois, Lausanne University, Lausanne, Switzerland (S.P. Thus, formal statistical testing of the one remaining secondary end point was not conducted. Zum Vergleich von Nivolumab versus Ipilimumab bei Patienten mit BRAF V600-Mutation ist die Studie CA209-067 geeignet. For the primary end point of overall survival with nivolumab plus ipilimumab, as compared with chemotherapy, among the patients with a PD-L1 expression level of 1% or more, we determined that a sample size of 800 patients (with 553 deaths) would provide a power of 90% to detect a hazard ratio of 0.74 at a two-sided significance level of 2.5%. Assessment history. 16. Nivolumab in combination with ipilimumab is a potential cost-effective treatment option for patients with intermediate or poor risk renal cell carcinoma (RCC), according to a study presented at the virtual 2020 ESMO Annual Congress. Treatment-related serious adverse events of any grade were more common with nivolumab plus ipilimumab than with chemotherapy (24.5% vs. 13.9%), as were treatment-related adverse events leading to discontinuation (18.1% vs. 9.1%). Hellmann MD, Ciuleanu TE, Pluzanski A, et al. S5). Two treatment-related deaths occurred in the nivolumab monotherapy group. Nivolumab (Opdivo®) + Ipilimumab (Yervoy®) Immunotherapy for advanced melanoma activates your immune system to attack the cancer cells. In CheckMate 227, a randomized, open-label, phase 3 trial, we evaluated nivolumab or nivolumab-based regimens as first-line treatment for advanced NSCLC. Mai 2019 -Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) Vorteilen beim Gesamtüberleben stehen keine gravierenden Nachteile gegenüber. Details regarding tissue requirements for PD-L1 screening and chemotherapy regimens are provided in the Methods section in the Supplementary Appendix. The recommended schedule and dose for this combination is nivolumab, 3 mg/kg, followed by ipilimumab, 1 mg/kg, on the same day every 3 weeks for 4 doses, then nivolumab… Combining nivolumab with ipilimumab has proved to be effective in melanoma and renal-cell carcinoma in previous studies,8,9,22 yet a key question before this trial was whether the addition of CTLA-4 inhibition to PD-1 blockade contributes to benefit in patients with NSCLC. Crossover between the treatment groups during the trial was not permitted. At a minimum follow-up of 60 months, the median overall survival was more than 60.0 months (median not reached) in the nivolumab-plus-ipilimumab group and 36.9 months in the nivolumab … Blood tumor mutational burden (bTMB) and tumor PD-L1 as predictive biomarkers of survival in MYSTIC: first-line durvalumab (D) ± tremelimumab (T) versus chemotherapy (CT) in metastatic (m) NSCLC. Biomarkers for predicting an enhanced benefit for combination immunotherapy relative to chemotherapy remain elusive. S3). Opdivo (nivolumab) is a member of the anti-PD-1 monoclonal antibodies drug class and is commonly used for Colorectal Cancer, Esophageal Carcinoma, Head and Neck Cancer, and others. For objective response rates, we used the Clopper–Pearson method to calculate 95% exact two-sided confidence intervals. This result is consistent with previous reports involving patients with melanoma and renal-cell carcinoma, which also showed a benefit for nivolumab plus ipilimumab regardless of PD-L1 level.8,9 The precise underpinnings of the diminished dependence on PD-L1 expression with a combination of PD-1 and CTLA-4 inhibition, as compared with anti–PD-1 monotherapy, are unknown. Die Bindung des PD1-Rezeptors an PD-L1 und PD-L2, die von Antigen-präsentierenden Zellen an deren Oberfläche exprimiert werden sowie von Tumoren oder anderen Zellen aus dem Tumormilieu, führt zur Hemmung der T-Zellproliferation und Zytokinausschüttung. Although this trial was not powered to compare the two regimens, our findings show better efficacy with nivolumab plus ipilimumab than with nivolumab monotherapy within the same trial. Diese Website ist für vertrauenswürdige medizinische Informationen von der Stiftung Health On the Net zertifiziert. The main reason for exclusion was not meeting the trial criteria. J Thorac Oncol 2017;12:Suppl:S321-S322. Klicken Sie hier, um das zu überprüfen. Sie basiert auf Daten der Studie CheckMate -067, die im The New England Journal of Medicine veröffentlicht wurde (2). N Engl J Med 2018;379:2040-2051. No new safety concerns emerged with longer follow-up. Tumor mutation burden as a biomarker in resected non-small-cell lung cancer. This benefit was observed across most subgroups (Fig. 4. Vor fast 1 Woche habe ich die 2. von 4 geplanten Infusionen erhalten. Prices start at $12,990.29 Nach Beginn der Nivolumab-Therapie können systemische Kortikosteroide oder andere Immunsuppressiva jedoch eingesetzt werden, um immunvermittelte Nebenwirkungen zu behandeln. Substantial progress has been made in the first-line treatment of patients with advanced non–small-cell lung cancer (NSCLC) without driver alterations that can be targeted. 25. Molecular determinants of response to anti-programmed cell death (PD)-1 and anti-programmed death-ligand 1 (PD-L1) blockade in patients with non-small-cell lung cancer profiled with targeted next-generation sequencing. The primary end point reported here was overall survival with nivolumab plus ipilimumab as compared with chemotherapy in patients with a PD-L1 expression level of 1% or more.

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