14. 23. Medikamenten, One of the sponsors (Bristol-Myers Squibb) and a steering committee designed the trial and analyzed the data, with the participation of all the authors. Tecentriq (atezolizumab) prescribing information. 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. In patients with a PD-L1 expression level of less than 1%, the median duration of overall survival was longer with nivolumab plus ipilimumab (17.2 months; 95% CI, 12.8 to 22.0) than with chemotherapy (12.2 months; 95% CI, 9.2 to 14.3), with a hazard ratio for death of 0.62 (95% CI, 0.48 to 0.78) (Figure 2A). A computational approach to distinguish somatic vs. germline origin of genomic alterations from deep sequencing of cancer specimens without a matched normal. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. NEW! You have ipilimumab over 30 or 90 minutes depending on your cancer type. Im Dosisbereich von 0,1 bis 10 mg/kg ist die Pharmakokinetik von Nivolumab linear. Costo del sovrappeso in pazienti in terapia con ipilimumab per melanoma avanzato in tre centri oncologici italiani NICOLETTA JANNITTI U.O.C. Information and tools for librarians about site license offerings. Adverse events were assessed by the investigator and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Overall survival rates at 1 year and 2 years were 62.6% and 40.0%, respectively, with nivolumab plus ipilimumab, as compared with 56.2% and 32.8%, respectively, with chemotherapy. Im Folgenden sind die Nebenwirkungen bei einer Kombinationstherapie entsprechend ihrer Häufigkeit gelistet: Als monoklonaler Antikörper wird Nivolumab nicht von Cytochrom-P450-Enzymen (CYPs) oder anderen Enzymen des Arzneimittelmetabolismus abgebaut. 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. Ipilimumab and nivolumab Ipilimumab and nivolumab are types of cancer treatment called immunotherapy. ); the Asan Medical Center (S.-W.K.) Die Europäische Kommission hat der Kombination von Nivolumab (Opdivo®) und Ipilimumab (Yervoy®) als Erstlinientherapie für Patienten mit fortgeschrittenem Nierenzellkarzinom (RCC) mit intermediärem oder ungünstigem Risikoprofil die Zulassung erteilt. The primary end point reported here is overall survival with nivolumab plus ipilimumab, as compared with chemotherapy, in patients with a PD-L1 expression level of 1% or more. * 2. Fundamental mechanisms of immune checkpoint blockade therapy. Das progressionsfreie Überleben (PFS) nahm von 2,9 Monaten unter Ipilimumab auf 6,9 Monate unter Nivolumab und auf 11,5 Monate unter Nivolumab plus Ipilimumab zu. Moreover, a substantial fraction of Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. 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. Ipilimumab was estimated to cost the most per patient, driven by the cost of the drug. This retrospective study included 1,474 patients who received nivolumab with or without ipilimumab. Data are needed to assess the long-term benefit of nivolumab plus ipilimumab in patients with NSCLC. Initial marketing-authorisation documents. 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. The percentage of patients who had a complete response with nivolumab plus ipilimumab, as compared with nivolumab monotherapy, was 5.8% and 3.0%, respectively, among the patients with a PD-L1 expression level of 1% or more and 8.8% and 4.7%, respectively, among those with a PD-L1 expression level of 50% or more. ); Bristol-Myers Squibb, Princeton, NJ (W.J.G., P.B., S.K.R., R.S.K., F.E.N. Treatment-Related Adverse Events in All the Recipients of Nivolumab plus Ipilimumab or Chemotherapy.*. First-line nivolumab plus ipilimumab in advanced non-small-cell lung cancer (CheckMate 568): outcomes by programmed death ligand 1 and tumor mutational burden as biomarkers. ); Hospital Universitario Doce de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and Centro de Investigación Biomédica en Red de Cáncer, Madrid (L.P.-A. PLoS Comput Biol 2018;14(2):e1005965-e1005965. Subsequent therapy was determined at the physician’s discretion. La combinazione di due molecole immuno-oncologiche, nivolumab e ipilimumab, riduce il rischio di progressione della malattia del 20%, di morte del 13% e … Sie basiert auf Daten der Studie CheckMate -067, die im The New England Journal of Medicine veröffentlicht wurde (2). 68,5% der eingeschlossenen Patienten hatten keine BRAF V600-Mutation. This benefit was observed across most subgroups (Fig. Risk of Death According to Tumor PD-L1 Expression Level and Tumor Mutational Burden. r The phase II CheckMate 069 study showed similar efficacy and toxicity for patients receiving combination ipilumumab/nivolumab and ipilimumab monotherapy respectively. Gide TN, Quek C, Menzies AM, et al. N Engl J Med 2018;378:1277-1290. * The determination that an adverse event was related to a trial treatment was made by the investigators. 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). For objective response rates, we used the Clopper–Pearson method to calculate 95% exact two-sided confidence intervals. Chalmers ZR, Connelly CF, Fabrizio D, et al. OPDIVO® 10 mg/ml Konzentrat zur Herstellung einer Infusionslösung, Opdivo 10mg/ml Lunapharm Konzentrat zur Herstellung einer Infusionslösung, Nivolumab 10 mg/ml Flüssigkonzentrat zur Infusion (Parenterale Anwendung). Ergebnisse wurden in einem Peer-Review-Journal publiziert [3]. In the nivolumab-plus-ipilimumab group, the median number of doses was 4 (range, 1 to 39) of nivolumab and 4 (range, 1 to 4) of ipilimumab; 147 of 313 patients (47.0%) received more than 4 … The results of the analysis of progression-free survival also favored nivolumab plus ipilimumab over chemotherapy (Fig. The trial was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonisation Good Clinical Practice guidelines. Ungefähr einheitliche Talspiegel im Steady-State wurden bei einer an das Körpergewicht angepassten Dosierung erzielt. 3. Der Hersteller informiert. Medizinische Medien Informations GmbH (MMI) und bietet News, Infos und N Engl J Med 2019;381:1535-1546. Compare prices, print coupons and get savings tips for Nivolumab (Opdivo) and other Melanoma drugs at CVS, Walgreens, and other pharmacies. Paz-Ares L, Luft A, Vicente D, et al. Distinct immune cell populations define response to anti-PD-1 monotherapy and anti-PD-1/anti-CTLA-4 combined therapy. The content of this site is intended for health care professionals. PD-L2 werden T-Zellreaktionen einschließlich Tumorabwehrreaktionen potenziert. ); Matrai Gyogyintezet, Matrahaza, Hungary (I.A. The median duration of response was longer with nivolumab plus ipilimumab than with nivolumab plus chemotherapy (18.0 months vs. 8.3 months). Nahrungsergänzungsmitteln, Verbandmitteln und Kosmetika. A pivotal trial compared nivolumab with ipilimumab; however, no head-to-head trial exists comparing nivolumab to observation, a common comparator in the adjuvant setting. Nivolumab and ipilimumab generated a gain of 0.978 QALYs over sunitinib in the U.S., with an incremental cost of $123,021. Into your bloodstream . The objective response rate was 27.3% with nivolumab plus ipilimumab and 37.9% with nivolumab plus chemotherapy. Motzer RJ, Tannir NM, McDermott DF, et al. Whitehouse Station, NJ: Merck, June 2019 (package insert) (https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf). The median duration of response was 23.2 months with nivolumab plus ipilimumab and 6.2 months with chemotherapy. Yost KE, Satpathy AT, Wells DK, et al. Patients were treated at a single center between January 2010 to August 2018. The tube stays in place throughout the course of treatment. 6 Wochen nach der letzten Dosis der Kombination von Nivolumab und Ipilimumab, wenn 480 mg alle 4 Wochen gegeben werden. 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… Genome Med 2017;9:34-34. 6. November 21, 2019N Engl J Med 2019; 381:2020-2031 . The current study aimed to assess the cost-effectiveness of nivolumab plus ipilimumab for first-line treatment of advanced RCC from the payer perspectives high- and middle-income regions. 30.11.2020 - Bei OPDIVO 10 mg/ml Konzentrat zur Herstellung einer Infusionslösung wurden die Indikationen erweitert. Zum Vergleich von Nivolumab versus Ipilimumab bei Patienten mit BRAF V600-Mutation ist die Studie CA209-067 geeignet. 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. Sade-Feldman M, Yizhak K, Bjorgaard SL, et al. J Thorac Oncol 2017;12:Suppl:S321-S322. Behandlungsbedingte unerwünschte Ereignisse traten bei 509 von 547 Patienten (93%) in der Nivolumab-plus-Ipilimumab-Gruppe sowie bei 521 von 535 Patienten (97%) in der Sunitinibgruppe auf. The patients who had a PD-L1 expression level of less than 1% were randomly assigned in a 1:1:1 ratio to receive nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy alone. We performed Kaplan–Meier analysis to estimate the duration of overall survival and progression-free survival, along with the duration of response. Die am häufigsten aufgetretenen Nebenwirkungen waren Fatigue, Hautausschlag, Pruritus, Diarrhö und Übelkeit. In einer Populationsanalyse betrug die mittlere geometrische Clearance (CL) 7,9 ml/h, die terminale Halbwertzeit 25 Tage und die durchschnittliche Exposition im Steady-State von Nivolumab (3 mg/kg Körpergewicht alle 2 Wochen) 86,6 µg/ml. ), Hospital Universitario Virgen Del Rocio, Seville (R.B.C. ); Fox Chase Cancer Center, Philadelphia (H.B. 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). For further information, see the summary of product characteristics. A data sharing statement provided by the authors is available with the full text of this article at NEJM.org. Deshalb ist nicht zu erwarten, dass gleichzeitig verabreichte Arzneimittel die Pharmakokinetik von Nivolumab durch Hemmung oder Induktion dieser Enzyme verändert. Durch ein malignes Melanom entstandene Metastasen werden bei mir (nach 10 x Kopfbestrahlung) seit Kurzem mit Nivolumab/Ipilimumab behandelt. Gegenanzeigen sind Überempfindlichkeit gegen den Wirkstoff  Nivolumab oder einen der sonstigen Bestandteile der Arzneizubereitung. Further understanding of the role of the tumor mutational burden, if any, as a biomarker is warranted before the integration of this factor into clinical practice. 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. The most common treatment-related select adverse events of any grade with a potential immunologic cause in the group that received nivolumab plus ipilimumab were skin reactions (in 34.0% of the patients) and endocrine events (in 23.8%) (Table S10). 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]. 19. Farmacia I.F.O., Unità Manipolazione Chemioterapici Antiblastici, Assicurazione di Duale Blockade von PD-1 und CTLA-4-vermittelten Signalwegen führte in genidentischen Maus­modellen zu synergistischer Tumoraktivität. South San Francisco, CA: Genentech, May 2019 (package insert) (https://www.gene.com/download/pdf/tecentriq_prescribing.pdf). 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. 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. Prices start at $12,990.29 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. Zum Vergleich von Nivolumab versus Dacarbazin ist die Studie CA209-066 geeignet. Tabla 3: Dosis recomendadas y tiempos de perfusión para la … Alter, Geschlecht, Rasse, Art des soliden Tumors, Tumorgröße und eingeschränkte Leberfunktion hatten keinen Einfluss auf die CL. CNS denotes central nervous system. Among the 679 patients (58.2%) in whom the tumor mutational burden was evaluated, a similar degree of overall survival benefit was observed in patients who received nivolumab plus ipilimumab, regardless of whether they had a high tumor mutational burden or a low tumor mutational burden (≥10 vs. <10 mutations per megabase, respectively), despite the previous observation of improved progression-free survival in patients with a high tumor mutational burden.11. Es ist nicht zu erwarten, dass sein Stoffwechsel durch andere Wirkstoffe beeinflusst wird. 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). Crossover between the treatment groups during the trial was not permitted. 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. Outcomes. 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. Es gibt aber auch gute Tage, an denen ich … Deshalb sollten Patienten mindestens bis 5 Monate nach der letzten Dosis engmaschig überwacht werden. The contribution of ipilimumab was evaluated in an analysis of nivolumab plus ipilimumab, as compared with nivolumab monotherapy, in patients with a PD-L1 expression level of 1% or more (Fig. The 2-year overall survival rates were 40.4% for nivolumab plus ipilimumab and 23.0% for chemotherapy. 25. They are used together to treat: melanoma skin cancer that has spread (advanced) or can't be removed with surgery Biomarkers for predicting an enhanced benefit for combination immunotherapy relative to chemotherapy remain elusive. Michael Atkins, MD Long-term follow-up results from CA209-004, a phase I study analyzing patients with advanced, unresectable melanoma treated with nivolumab (Opdivo) plus ipilimumab (Yervoy), showed favorable survival Nivolumab bindet an den Rezeptor PD-1 auf T-Lymphozyten und verhindert so dessen abwehrhemmende Wirkung. N Engl J Med 2018;378:2078-2092. * NA denotes not applicable because all the patients in this group had a PD-L1 expression level of 1 or more. Treatment-related deaths occurred in 8 patients who received nivolumab plus ipilimumab and in 6 patients who received chemotherapy (Table 2). Schwere Nebenwirkungen (Grad 3 oder 4) traten bei 250 Patienten (46%) bzw. At 2 years, the overall survival rate was 40.4% and 34.7%, respectively. Socinski MA, Jotte RM, Cappuzzo F, et al. In both portions of the trial, patients were stratified according to tumor histologic features (squamous vs. nonsquamous) (Fig. The safety of nivolumab plus ipilimumab has been improved in patients with NSCLC with the use of a lower dose and frequency of administration of ipilimumab, as was suggested in the phase 1 dose-finding study.10, In addition, the duration of overall survival was longer with nivolumab plus ipilimumab than with chemotherapy in all the trial patients, including in those with a PD-L1 expression level of less than 1%, a population for whom anti–PD-1 monotherapy has been insufficient. Lancet 2019;393:1819-1830. 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. Hellmann MD, Rizvi NA, Goldman JW, et al. Beides führt dazu, dass die Immunzellen sich stärker vermehren und aktiver werden, sodass sie die Tumorzellen energischer bekämpfen können. Metastatic cutaneous melanoma was noted in 12 patients; 2 were cases of uveal melanoma and 1 was a non-small-cell lung carcinoma. The overall survival rate at 5 years was 52% in the nivolumab-plus-ipilimumab group and 44% in the nivolumab group, compared with 26% in the ipilimumab group. CTLA-4 has very high structural homology to the costi-mulatory molecule CD28, and it could also bind B7 molecules present on antigen-presenting cells (APCs) with much higher affinity and avidity than CD28 (Schildberg et al., 2016; Sharma and Allison, 2015a). Ipilimumab (Yervoy) i kombinasjon med nivolumab (Opdivo) kan innføres til behandling av tidligere ubehandlede pasienter med avansert eller metastatisk nyrecellekarsinom med intermediær / høy risiko. Kombination Nivolumab mit Ipilimumab nur bei Patienten mit niedriger Tumor PD-L1-Expression ein Anstieg des progressionsfreien Überlebens (PFS) gezeigt (1). Studien zur Untersuchung der Fertilität wurden nicht durchgeführt. Nivolumab plus Ipilimumab bei Melanom: Zusatznutzen bei bestimmten Patienten Überlebensvorteil bei BRAF-V600-wt-Tumor hängt vom Geschlecht ab / Schwere Nebenwirkungen häufiger Seit Mai 2016 ist Nivolumab (Handelsname Opdivo) in Kombination mit Ipilimumab (Handelsname Yervoy) für Erwachsene mit fortgeschrittenem Melanom (schwarzer Hautkrebs) zugelassen. There is the potential for improved responses with the use of combination immunotherapy. The median duration of overall survival and rates of overall survival at 1 year and 2 years with nivolumab plus ipilimumab were nearly identical in these two PD-L1 subgroups. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; … Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer N Engl J Med. You have ipilimumab and nivolumab through a drip into your bloodstream (intravenously). The overall survival rate at 5 years was 52% in the nivolumab-plus-ipilimumab group and 44% in the nivolumab group, compared with 26% in the ipilimumab group. 8. PURPOSE Metastatic uveal melanoma has poor overall survival (OS) and no approved systemic therapy options. Sun JX, He Y, Sanford E, et al. Im Rahmen dieser doppelblinden, randomisierten Phase … (nivolumab, pembrolizumab) as single agents or combined with ipilimumab. The most trusted, influential source of new medical knowledge and clinical best practices in the world. Foundation Medicine. ‡ On the performance-status evaluation of the Eastern Cooperative Oncology Group (ECOG), a score of 0 indicates that the patient is fully active, and a score of 1 indicates that the patient is restricted in physically strenuous activity but ambulatory. Prespecified analyses that were not part of the statistical testing hierarchy are descriptive (Table S1). Pembrolizumab plus chemotherapy for squamous non–small-cell lung cancer. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. In Part 1b, patients were randomly assigned in a 1:1:1 ratio to receive nivolumab plus ipilimumab, nivolumab (360 mg every 3 weeks) plus platinum-doublet chemotherapy (every 3 weeks for up to four cycles), or platinum-doublet chemotherapy alone (every 3 weeks for up to four cycles). We thank the patients and their families for making this trial possible; the investigators and clinical trial teams who participated in the trial; Suresh Alaparthy, Judith Bushong, and Christopher Coira of Bristol-Myers Squibb for their contributions as protocol managers of the trial; Joseph Szustakowski, Han Chang, and George Green for their analyses of the tumor mutational burden; Foundation Medicine for the collaborative development of the FoundationOne CDx assay; Dako for the collaborative development of the PD-L1 IHC 28-8 pharmDx assay; and Namiko Abe and Laura Yee of Caudex for their assistance in the preparation of the manuscript, including contributions to the first draft. 2. Key exclusion criteria were the presence of EGFR mutations or known ALK translocations sensitive to targeted therapy, autoimmune disease, or untreated or symptomatic central nervous system metastases. Derzeit überleben weniger als 50 Prozent der Patienten mit metastasiertem Nierenzellkarzi… J Clin Oncol 2019;37:Suppl:9016-9016. abstract. S8). Exploratory analysis of additional PD-L1 expression thresholds that are currently used for selection of anti–PD-1 monotherapy showed more variable benefit (Figure 3). N Engl J Med 2018;378:2288-2301. All treatment-related adverse events and serious adverse events were reported during the time between the first dose of a trial treatment and 30 days after the last dose. Rizvi H, Sanchez-Vega F, La K, et al. The minimum follow-up for safety analyses was 28.3 months, except for treatment-related serious adverse events, which had a minimum follow-up of 29.3 months. r The phase II CheckMate 069 study showed similar efficacy and toxicity for patients receiving combination ipilumumab/nivolumab and ipilimumab monotherapy respectively. Nivolumab has been approved in patients with melanoma with lymph node involvement or metastatic disease who have undergone complete resection, in the adjuvant setting. No new safety concerns emerged with longer follow-up. N Engl J Med 2016;375:1823-1833. Klicken Sie hier, um das zu überprüfen. Nebenwirkungen können unter Nivolumab oder Nivolumab in Kombination mit Ipilimumab jederzeit während oder nach der Behandlung auftreten. S3) and in those with a PD-L1 expression level of 50% or more (Fig. The authorized source of trusted medical research and education for the Chinese-language medical community. The minimum follow-up for overall survival was 29.3 months. Studies of single-agent immunotherapy regimens have shown minimal benefit. Also shown are the 1-year and 2-year rates of survival in the two groups. S5). Shown is the median duration of overall survival in patients in the group that received nivolumab plus ipilimumab and in the group that received chemotherapy among those who had a tumor PD-L1 expression level of less than 1% (Panel A) and among those in the overall population (Panel B). From the Memorial Sloan Kettering Cancer Center, New York (M.D.H. ); Sotiria General Hospital, National and Kapodistrian University of Athens, Athens (K.S. No new safety concerns emerged with longer follow-up. ¶ The number of mutations (mut) was determined with the use of the FoundationOne CDx assay. The characteristics of the patients were balanced across the treatment groups at baseline (Table 1 and Tables S4 and S5). Analyses of all other end points were also descriptive. Table 2. Shown is the risk of death among the patients who received nivolumab plus ipilimumab and in those who received chemotherapy according to the tumor PD-L1 expression level, tumor mutational (mut) burden, or both in prespecified randomized groups or in exploratory groups. In particular, we observed higher rates of complete response and a longer median duration of response (a difference of >7 months) in the patients who received nivolumab plus ipilimumab. 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. 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%. 17.04.2018 Nivolumab plus Ipilimumab war mit einem besseren Überleben als Chemotherapie bei NSCLC mit hoher Tumormutationsbelastung verbunden laut einer im New England Journal of Medicine veröffentlichten Studie. Es existieren nur begrenzt Daten hinsichtlich schwer eingeschränkter Nierenfunktion, als dass sich daraus Schlüsse für diese Population ableiten lassen. 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. Die Anwendung von Nivolumab in der Schwangerschaft wird nicht empfohlen, es sei denn, der klinische Nutzen überwiegt das potentielle Risiko. (Details are provided in the Methods section in the Supplementary Appendix.) Of the 550 patients with a PD-L1 expression level of less than 1%, 187 were assigned to receive nivolumab plus ipilimumab, 177 to receive nivolumab plus chemotherapy, and 186 to receive chemotherapy. 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. 335 Patienten (63%) auf. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. An ECOG score of 2 or more was reported in 4 patients in the group with PD-L1 expression of 1% or more and in 6 patients in the overall population; data were missing for 3 patients and 2 patients in the two populations, respectively. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. A decision-analytic … Zur Anwendung von Nivolumab bei Schwangeren liegen keine Daten vor und das potentielle Risiko für den sich entwickelnden Fötus ist nicht bekannt.