); the Asan Medical Center (S.-W.K.) Schwere Nebenwirkungen (Grad 3 oder 4) traten bei 250 Patienten (46%) bzw. ); Sotiria General Hospital, National and Kapodistrian University of Athens, Athens (K.S. Paz-Ares L, Luft A, Vicente D, et al. Nivolumab and ipilimumab generated a gain of 0.978 QALYs over sunitinib in the U.S., with an incremental cost of $123,021. Nivolumab has been approved in patients with melanoma with lymph node involvement or metastatic disease who have undergone complete resection, in the adjuvant setting. Gegenanzeigen sind Überempfindlichkeit gegen den Wirkstoff Nivolumab oder einen der sonstigen Bestandteile der Arzneizubereitung. Ipilimumab was estimated to cost the most per patient, driven by the cost of the drug. 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. Combining the two key biomarkers (PD-L1 expression level and tumor mutational burden) did not identify a subgroup that had an increased magnitude of benefit with nivolumab plus ipilimumab over chemotherapy, although the sample sizes become more modest in these analyses. Reck M, Rodríguez-Abreu D, Robinson AG, et al. ); Limoges University Hospital, Limoges (A.V. 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. 0,0001). Klicken Sie hier, um das zu überprüfen. * 2. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; … Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer N Engl J Med. r The phase II CheckMate 069 study showed similar efficacy and toxicity for patients receiving combination ipilumumab/nivolumab and ipilimumab monotherapy respectively. You might have treatment through a long plastic tube that goes into a large vein in your chest. Outcomes. Hellmann MD, Ciuleanu TE, Pluzanski A, et al. 8. Mai 2019 -Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) Vorteilen beim Gesamtüberleben stehen keine gravierenden Nachteile gegenüber. In this open-label, phase 3 trial, we randomly assigned patients with stage IV or recurrent NSCLC and a PD-L1 expression level of 1% or more in a 1:1:1 ratio to receive nivolumab plus ipilimumab, nivolumab alone, or chemotherapy. 22. Compare prices, print coupons and get savings tips for Nivolumab (Opdivo) and other Melanoma drugs at CVS, Walgreens, and other pharmacies. Prespecified analyses that were not part of the statistical testing hierarchy are descriptive (Table S1). † For nivolumab plus ipilimumab, these events included treatment-related adverse events leading to the discontinuation of ipilimumab alone or the discontinuation of both nivolumab and ipilimumab; the discontinuation of nivolumab alone was not permitted. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. 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. ); and Winship Cancer Institute, Emory University, Atlanta (S.S.R.). Beides führt dazu, dass die Immunzellen sich stärker vermehren und aktiver werden, sodass sie die Tumorzellen energischer bekämpfen können. They are used together to treat: melanoma skin cancer that has spread (advanced) or can't be removed with surgery N Engl J Med 2018;378:2078-2092. 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. Crossover between the treatment groups during the trial was not permitted. ); Fox Chase Cancer Center, Philadelphia (H.B. 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. Samstein RM, Lee CH, Shoushtari AN, et al. 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 … Lancet Oncol 2017;18:31-41. Initial marketing-authorisation documents. and the Samsung Medical Center at Sungkyunkwan University School of Medicine (K.P.) Keytruda (pembrolizumab) prescribing information. Distinct immune cell populations define response to anti-PD-1 monotherapy and anti-PD-1/anti-CTLA-4 combined therapy. Eligibility criteria for CheckMate 227 have been described previously.11 Patients were adults with squamous or nonsquamous stage IV or recurrent NSCLC and an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1 (on a 5-point scale, with higher scores indicating greater disability).12 None of the patients had received previous systemic anticancer therapy for advanced or metastatic disease. 15. Also shown are the 1-year and 2-year rates of survival in the two groups. Patients were treated at a single center between January 2010 to August 2018. Among the patients with a PD-L1 expression level of 1% or more, the median duration of overall survival was 17.1 months (95% confidence interval [CI], 15.0 to 20.1) with nivolumab plus ipilimumab and 14.9 months (95% CI, 12.7 to 16.7) with chemotherapy (P=0.007), with 2-year overall survival rates of 40.0% and 32.8%, respectively. Gelbe Liste Online ist ein Online-Dienst der
Die Mehrheit der Nebenwirkungen war leicht bis mäßig. Risk of Death According to Tumor PD-L1 Expression Level and Tumor Mutational Burden. The main reason for exclusion was not meeting the trial criteria. Table 1. 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. In both portions of the trial, patients were stratified according to tumor histologic features (squamous vs. nonsquamous) (Fig. Es ist nicht bekannt, ob der Wirkstoff in die Muttermilch übergeht. Nivolumab plus ipilimumab improves overall survival and is associated with less toxicity compared with sunitinib in the first-line setting of advanced renal-cell carcinoma (RCC). Percentages may not total 100 because of rounding. 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. Duale Blockade von PD-1 und CTLA-4-vermittelten Signalwegen führte in genidentischen Mausmodellen zu synergistischer Tumoraktivität. 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. Nivolumab plus Ipilimumab in Advanced Non–Small-Cell Lung Cancer. The median duration of response was 23.2 months with nivolumab plus ipilimumab and 6.2 months with chemotherapy. An overall survival benefit with nivolumab plus ipilimumab, as compared with chemotherapy, was observed regardless of the subgroup of PD-L1 expression level. Medikamenten,
Socinski MA, Jotte RM, Cappuzzo F, et al. This retrospective study included 1,474 patients who received nivolumab with or without ipilimumab. ‡ Treatment-related deaths in the group that received nivolumab plus ipilimumab were from pneumonitis (in 4 patients) and from shock, myocarditis, acute tubular necrosis, and cardiac tamponade (in 1 patient each). Lancet 2019;393:1819-1830. Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. However, toxicities made up a much larger proportion of the cost of care for nivolumab and pembrolizumab. Cancer Discov 2018;8:1069-1086. 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. Deshalb ist nicht zu erwarten, dass gleichzeitig verabreichte Arzneimittel die Pharmakokinetik von Nivolumab durch Hemmung oder Induktion dieser Enzyme verändert. No new safety concerns emerged with longer follow-up. 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. Treatment-Related Adverse Events in All the Recipients of Nivolumab plus Ipilimumab or Chemotherapy.*. Durch die von Nivolumab induzierte Blockade der Bindung zwischen PD-1 und PD-L1 bzw. 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. Nivolumab, a fully human anti–PD-1 antibody, and ipilimumab, a fully human anti–cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody, are immune checkpoint inhibitors with distinct but complementary mechanisms of action. Sade-Feldman M, Yizhak K, Bjorgaard SL, et al. N Engl J Med 2019;381:1535-1546. 13. 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. Nivolumab bindet an den Rezeptor PD-1 auf T-Lymphozyten und verhindert so dessen abwehrhemmende Wirkung. Ovvero che il 54% dei pazienti ha avuto gravi ripercussioni collaterali del tipo “pausa ad effetto” , ha detto Suzanne Topalian, direttore del programma melanoma presso la Johns Hopkins Kimmel Cancer Center di Baltimora e ricercatore leader nell’immunoterapia. This article was published on September 28, 2019, and last updated on April 17, 2020, at NEJM.org. 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
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 … 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. Thus, formal statistical testing of the one remaining secondary end point was not conducted. Im Dosisbereich von 0,1 bis 10 mg/kg ist die Pharmakokinetik von Nivolumab linear. 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. Tumor mutation burden (TMB) is associated with improved efficacy of atezolizumab in 1L and 2L+ NSCLC patients. Das Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) hat zuletzt 2018 geprüft, welche Vor- und Nachteile Nivolumab (Handelsname Opdivo) in Kombination mit Ipilimumab (Handelsname Yervoy) bei Personen mit fortgeschrittenem schwarzem Hautkrebs hat. 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. . Ipilimumab and nivolumab Ipilimumab and nivolumab are types of cancer treatment called immunotherapy. In the primary analysis from this trial, the median duration of overall survival was significantly longer with nivolumab plus ipilimumab than with chemotherapy among patients with advanced NSCLC who had a PD-L1 expression level of 1% or more. In patients with a PD-L1 expression level of 1% or more, the rate of overall survival at 2 years was 40.0% with nivolumab plus ipilimumab and 36.2% with nivolumab monotherapy. Es existieren nur begrenzt Daten hinsichtlich schwer eingeschränkter Nierenfunktion, als dass sich daraus Schlüsse für diese Population ableiten lassen. Aus diesem Grunde sollte die Anwendung systemischer Kortikosteroide und anderer Immunsuppressiva vor Beginn der Behandlung mit Nivolumab vermieden werden. 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. Tabelle 2: Empfohlene Dosis und Infusionszeit für die intravenöse Verabreichung von Nivolumab in Kombination mit Ipilimumab für Melanom Kombinationsphase, alle 3 Wochen für 4 Dosierungszyklen Monotherapiephase Nivolumab 1 mg/kg über 30 Minuten 240 mg alle … 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. † Nivolumab monotherapy was evaluated only in the primary-analysis population involving patients with a PD-L1 (programmed death ligand 1) tumor expression of 1% or more. Treatment continued until disease progression or unacceptable toxicity or, for the immunotherapy regimens, until 2 years of follow-up. Medizinprodukten, Diätetika,
Farmacia I.F.O., Unità Manipolazione Chemioterapici Antiblastici, Assicurazione di 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. We determined the PD-L1 expression level13 and tumor mutational burden11,14-16 as described previously. DOI: 10.1056/NEJMoa1910231, Tap into groundbreaking research and clinically relevant insights. Datenbanken für Ärzte,
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 … r Alter, Geschlecht, Rasse, Art des soliden Tumors, Tumorgröße und eingeschränkte Leberfunktion hatten keinen Einfluss auf die CL. CL stieg mit höherem Körpergewicht an. — all in Spain; Ambulatorium Chemioterapii, Bydgoszcz, Poland (B.Z. 16.11.2020 - Bei OPDIVO 10 mg/ml Konzentrat zur Herstellung einer Infusionslösung haben sich die Indikationen erweitert. Deshalb sollten Patienten mindestens bis 5 Monate nach der letzten Dosis engmaschig überwacht werden. If a hierarchical end point was not met, the remaining end points in the hierarchy were considered to be descriptive only. The unexpected effect of the tumor mutational burden on the overall survival of patients who received chemotherapy may have contributed to these results. ¶ The number of mutations (mut) was determined with the use of the FoundationOne CDx assay. A subgroup … Sun JX, He Y, Sanford E, et al. We planned to enroll 1200 patients for randomization into the three treatment groups in Part 1a. List item. In patients with a PD-L1 expression level of 1% or more, the median duration of overall survival was 17.1 months (95% confidence interval [CI], 15.0 to 20.1) with nivolumab plus ipilimumab and 14.9 months (95% CI, 12.7 to 16.7) with chemotherapy (P=0.007) (Figure 1A). The median duration of response was longer with nivolumab plus ipilimumab than with nivolumab plus chemotherapy (18.0 months vs. 8.3 months). Adverse events leading to the discontinuation of ipilimumab earlier than the discontinuation of nivolumab occurred in 18 patients (3.1%). Studies of single-agent immunotherapy regimens have shown minimal benefit. Stay connected to what's important in medical research and clinical practice, Subscribe to the most trusted and influential source ofmedical knowledge. (Details are provided in the Methods section in the Supplementary Appendix.) Ungefähr einheitliche Talspiegel im Steady-State wurden bei einer an das Körpergewicht angepassten Dosierung erzielt. Concise summaries and expert physician commentary that busy clinicians need to enhance patient care. 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. Dr. Matthew D. Hellman vom Memorial Sloan Kettering Cancer Center in New York City und Kollegen randomisierten Patienten mit Stadium IV oder … The tube stays in place throughout the course of treatment. Datenbank mit Informationen, Adressen und Präparaten der Pharma-Hersteller. Cell 2018;175(4):998.e20-1013.e20. In this phase 3, randomized trial, we found that patients with advanced NSCLC and a PD-L1 expression level of 1% or more who received nivolumab plus ipilimumab had a significantly longer duration of overall survival than those who received chemotherapy as first-line treatment. The overall survival benefit was also observed in patients with a PD-L1 expression level of less than 1%, with a median duration of 17.2 months (95% CI, 12.8 to 22.0) with nivolumab plus ipilimumab and 12.2 months (95% CI, 9.2 to 14.3) with chemotherapy. Bristol-Myers Squibb, Fachinformation; EMA. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. Nivolumab BMS is indicated for the treatment of locally advanced or metastatic squamous non-small cell lung cancer (NSCLC) after prior chemotherapy in adults. The hazard ratio for the group with a PD-L1 expression level of 1% or more is shown with a 97.72% confidence interval; stratified hazard ratios for all the patients and those with a PD-L1 expression level of 1% or more are shown. 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). The results of the analysis of progression-free survival also favored nivolumab plus ipilimumab over chemotherapy (Fig. Prices start at $12,990.29 At 2 years, the overall survival rate was 40.4% and 34.7%, respectively. N Engl J Med 2018;378:2288-2301. Overall Survival in Patients with a Tumor PD-L1 Expression Level of Less Than 1% and in All the Patients. In secondary analyses, the duration of overall survival was also longer with nivolumab plus ipilimumab than with chemotherapy in patients with a PD-L1 expression of less than 1% and in all the trial patients. Up-front immunotherapy is the most cost-effective option for treating newly diagnosed unresectable stage III or IV melanoma with unknown BRAF mutation status, concludes a … ); Instituto Jalisciense de Cancerologia, Guadalajara, Mexico (E.M.J. 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). Larkin J, Chiarion-Sileni V, Gonzalez R, et al. 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). Über 110.000 Arzneimittel und Medizinprodukte mit Anwendungs- und Fachinformationen. Ipilimumab wird alle drei Monate intravenös verabreicht. Ipilimumab (Yervoy) i kombinasjon med nivolumab (Opdivo) kan innføres til behandling av tidligere ubehandlede pasienter med avansert eller metastatisk nyrecellekarsinom med intermediær / høy risiko. Alter, Geschlecht, Rasse, Art des soliden Tumors, Tumorgröße und eingeschränkte Leberfunktion hatten keinen Einfluss auf die CL. 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. Chalmers ZR, Connelly CF, Fabrizio D, et al. Among the patients who had disease progression during the trial, subsequent systemic therapy was administered in 43.6% of the patients who had received nivolumab plus ipilimumab and in 55.8% of those who had received chemotherapy; immunotherapy was administered in 42.4% of those in the chemotherapy group. Nivolumab bindet an den Rezeptor PD-1 auf T-Lymphozyten und verhindert so dessen abwehrhemmende Wirkung. S8). The cost for Opdivo intravenous solution (10 mg/mL) is around $1,154 for a supply of 4 milliliters, depending on the pharmacy you visit. 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. The objective response rate was 35.9% (95% CI, 31.1 to 40.8) with nivolumab plus ipilimumab (with 5.8% of patients having a complete response) versus 30.0% (95% CI, 25.5 to 34.7) with chemotherapy (with 1.8% of patients having a complete response) (Table S9). South San Francisco, CA: Genentech, May 2019 (package insert) (https://www.gene.com/download/pdf/tecentriq_prescribing.pdf). Details regarding the eligibility criteria are provided in the Methods section of the Supplementary Appendix, available with the full text of this article at NEJM.org. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. Systemic immunity is required for effective cancer immunotherapy. Data regarding treatment duration, number of doses, and subsequent therapies within PD-L1 subgroups and in all patients are provided in Tables S6, S7, and S8. PATIENTS AND METHODS We conducted a phase II study of nivolumab with ipilimumab in patients with … ); Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany (M.R. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. — both in Seoul, South Korea; the Institute of Oncology Prof. Dr. Alexandru Trestioreanu, Bucharest, Romania (A.A.); the Hospital Italiano de Buenos Aires, Buenos Aires (L.L. 2. Cell 2017;168(3):487.e15-502.e15. 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%). 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. 10. ), and the Catalan Institute of Oncology–Germans Trias i Pujol Hospital, Badalona (E.C.C.) 12. Ergebnisse wurden in einem Peer-Review-Journal publiziert . Valuable tools for building a rewarding career in health care. Nivolumab (Handelsname Opdivo) ist ein Checkpoint-Inhibitor, der als Wirkstoff gegen verschiedene Tumoren eingesetzt wird.Es handelt sich um einen menschlichen (vollständig humanen) monoklonalen Antikörper, der an den PD-1-Rezeptor auf T-Zellen bindet und die Wechselwirkung mit dem eigentlich hier bindenden PD1-Rezeptor-Ligand verhindert. Combination therapy with nivolumab plus ipilimumab has resulted in longer overall survival than previous standard therapies in patients with melanoma8 and in those with renal-cell carcinoma.9 In a phase 1 study involving patients with NSCLC, the response rate was better with nivolumab plus ipilimumab than with nivolumab monotherapy, particularly among patients with PD-L1–expressing tumors.10 Decreasing the dose and frequency of administration of ipilimumab (1 mg per kilogram of body weight every 6 weeks) when combined with nivolumab resulted in fewer adverse events than other ipilimumab regimens while maintaining improved efficacy in patients with NSCLC.10. Overall survival in most subgroups favored nivolumab plus ipilimumab (Figure 1B); the exceptions were patients with liver metastases and those who had never smoked. 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. S5). Key Points Question Is pembrolizumab-axitinib cost-effective as first-line treatment of advanced renal cell carcinoma compared with nivolumab-ipilimumab, the other preferred first-line regimen? Ipilimumab schwächt dagegen die Hemmwirkung des Moleküls CTLA-4 auf den T-Lymphozyten. 68,5% der eingeschlossenen Patienten hatten keine BRAF V600-Mutation. * NA denotes not applicable because all the patients in this group had a PD-L1 expression level of 1 or more. Beim metastasierten Melanom kann die Kombination einer Nivolumab (anti-PD-1) und Ipilimumab (anti-CTLA-4) – vermittelten Hemmung eine verbesserte Anti-Tumor-Aktivität bewirken. 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. Schwerwiegende bis lebensbedrohliche immunvermittelte Nebenwirkungen können Verdauungstrakt, Leber, Haut, Nervensystem, endokrines System oder andere Organsysteme betreffen. 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 … Moreover, a substantial fraction of The minimum follow-up for overall survival was 29.3 months.