natgillin/translations-raw huggingface dataset:
Studiet viste statistisk signifikante forbedringer i OS og ORR for patienter, der var randomiseret til pembrolizumab sammenlignet med kemoterapi.
The study demonstrated statistically significant improvements in OS and ORR for patients randomised to pembrolizumab as compared to chemotherapy.
% igangværende respons
% ongoing
Patienterne skal monitoreres for ændringer i nyrefunktionen, og andre årsager til nedsat nyrefunktion skal udelukkes.
Patients should be monitored for changes in renal function, and other causes of renal dysfunction excluded.
18,9 (11, foreligger ikke)
18.9 (11, not available)
Immunrelaterede bivirkninger, inklusive svære og dødelige tilfælde, er forekommet hos patienter, der fik pembrolizumab.
Immune-related adverse reactions, including severe and fatal cases, have occurred in patients receiving pembrolizumab.
Hypotyroidisme kan behandles med substitution uden afbrydelse af behandlingen.
Hypothyroidism may be managed with replacement therapy without treatment interruption.
I henhold til AJCC-stadieklassificering, 8. udgave, blev i alt 82 forsøgspersoner klassificeret som stadie IIIA; 42 i armen med pembrolizumab og 40 i placebo-armen; med i alt 13 RFS-hændelser; 6 i armen med pembrolizumab og 7 i placebo-armen.
th edition classification, a total of 82 subjects were classified as stage IIIA; 42 in the pembrolizumab arm and 40 in the placebo arm; with a total of 13 RFS events; 6 in the pembrolizumab arm and 7 in the placebo arm.
Der skal udvises forsigtighed, hvis pembrolizumab-behandling overvejes hos en patient, der har oplevet en alvorlig eller livstruende hudreaktion under tidligere behandling med andre immunstimulerende cancerlægemidler.
Caution should be used when considering the use of pembrolizumab in a patient who has previously experienced a severe or life-threatening skin adverse reaction on prior treatment with other immunestimulatory anticancer agents.
Der var ingen statistisk signifikant forskel mellem pembrolizumab og kemoterapi i den endelige OS-analyse, som ikke var korrigeret for den potentielt konfunderende effekt af overkrydsningen.
There was no statistically significant difference between pembrolizumab and chemotherapy in the final OS analysis that was not adjusted for the potentially confounding effects of crossover.
Kaplan-Meier-kurverne for OS og PFS baseret på yderligere fire måneders opfølgning er vist i figur 16 og 17.
The Kaplan-Meier curves for OS and PFS based on an additional four months of follow up are shown in Figures 16 and 17.
Det skal besluttes, om amning skal ophøre eller behandling med pembrolizumab skal seponeres, idet der tages højde for fordelene ved amning for barnet i forhold til de terapeutiske fordele ved pembrolizumab-behandlingen for moderen.
A decision should be made whether to discontinue breast-feeding or to discontinue pembrolizumab, taking into account the benefit of breast-feeding for the child and the benefit of pembrolizumab therapy for the woman.
Ved urotelial cancer sås et højere antal dødsfald indenfor 2 måneder med pembrolizumab sammenlignet med kemoterapi (se pkt.
In urothelial cancer, a higher number of deaths within 2 months was observed in pembrolizumab compared to chemotherapy (see section 5.1).
Tabel 29: Effektresultater i KEYNOTE-426 ud fra IMDC-risikokategori
Table 29: Efficacy Results in KEYNOTE-426 by IMDC Risk Category
Pembrolizumab nedbrydes via non-specifikke metaboliseringsveje; metaboliseringen bidrager ikke til pembrolizumabs clearance.
Pembrolizumab is catabolised through non-specific pathways; metabolism does not contribute to its clearance.
Der var ingen statistisk signifikant forskel mellem pembrolizumab og kemoterapi med hensyn til PFS.
There was no statistically significant difference between pembrolizumab and chemotherapy with respect to PFS.
Det skal du vide, før du får Keytruda
What you need to know before you are given KEYTRUDA
45% havde ikke tidligere fået behandling for fremskredent melanom.
Forty-five percent had no prior therapies for advanced melanoma.
Ikke nået (NA; NA)
Not reached (NA, NA)
Keytruda styrker immunsystemets evne til at bekæmpe kræft.
KEYTRUDA works by helping your immune system fight your cancer.
Randomiseringen blev stratificeret ud fra PD-L1tumorekspression (TPS ≥ 50% eller < 50%), HPV-status (positiv eller negativ) og ECOG-PS (0 versus 1).
Randomization was stratified by tumour PD-L1 expression (TPS ≥ 50% or < 50%), HPV status (positive or negative), and ECOG PS (0 vs. 1).
Antal patienter
Number of patients OS
Respons: Bedste objektive respons, der er bekræftet komplet eller partielt respons
Response: Best objective response as confirmed complete response or partial response
Patienter med EGFR-aktiverende mutationer eller ALK-translokation havde også sygdomsprogression, mens de var i godkendt behandling for disse mutationer inden behandling med pembrolizumab.
Patients with EGFR activation mutation or ALK translocation also had disease progression on approved therapy for these mutations prior to receiving pembrolizumab.
2 patienter (< 0,1%) seponerede pembrolizumab som følge af hypotyroidisme.
Two patients (< 0.1%) discontinued pembrolizumab due to hypothyroidism.
Gennemsigtige til hvide proteinholdige partikler kan forekomme i den fortyndede infusionsvæske.
Translucent to white proteinaceous particles may be seen in diluted solution.
Data vedrørende pembrolizumabs virkning og sikkerhed i kombination med platinbaseret kemoterapi er begrænset i denne patientpopulation.
Data about efficacy and safety of pembrolizumab in combination with platinum chemotherapy are limited in this patient population.
Størstedelen af de rapporterede bivirkninger ved monoterapi var af sværhedsgrad 1 eller 2.
The majority of adverse reactions reported for monotherapy were of Grade 1 or 2 severity.
Efter administration af pembrolizumab 200 mg hver 3. uge til patienter med cHL var den observerede mediane Cmin ved steady state op til 40% højere end den, som blev observeret ved andre tumortyper, der blev behandlet med samme dosis.
Following administration of pembrolizumab 200 mg every 3 weeks in patients with cHL, the observed median Cmin at steady-state was up to 40% higher than that in other tumour types treated with the same dosage; however, the range of trough concentrations is similar.
Psykiske forstyrrelser Almindelig insomni insomni insomni
Psychiatric disorders Common insomnia insomnia insomnia
Baseret på bedst respons for stabil sygdom eller bedre Baseret på Kaplan-Meier-estimering; omfatter 84 patienter med 6 måneders respons eller længere
Based on best response of stable disease or better Based on Kaplan-Meier estimates; includes 84 patients with response of 6 months or longer
Grad ≥ 3 med ASAT eller ALAT > 5 gange ULN eller total-bilirubin > 3 gange ULN
Grade ≥ 3 with AST or ALT > 5 times ULN or total bilirubin > 3 times ULN
Insulin skal administreres ved type 1-diabetes, og behandlingen med pembrolizumab skal pauseres i tilfælde af grad 3-hyperglykæmi, indtil der er opnået metabolisk kontrol (se pkt.
Insulin should be administered for type 1 diabetes, and pembrolizumab should be withheld in cases of Grade 3 hyperglycaemia until metabolic control is achieved (see section 4.2).
Tabel 22: ORR og OS ved PD-L1-ekspression
Table 22: ORR and OS by PD-L1 Expression
76% af patienterne havde tidligere fået cisplatin, 23% havde tidligere fået carboplatin, og 1% var blevet behandlet med andre platinbaserede regimer.
Seventy-six percent of patients received prior cisplatin, 23% had prior carboplatin, and 1% was treated with other platinum-based regimens.
Blandt de patienter, som var evaluerbare for PD-L1-ekspression (79%), var 69% (n=294) PD-L1-positive, og 31% (n=134) var PD-L1-negative.
Among patients who were evaluable for PD-L1 expression (79%), 69% (n=294) were PD-L1 positive and 31% (n=134) were PD-L1 negative.
Immunsystemet Almindelig infusionsreaktioner infusionsreaktioner infusionsreaktioner
Immune system disorders Common infusion related reaction infusion related reaction a infusion related reaction
Se tabel 28 for p-værdien for inferentiel test af OS baseret på den præspecificerede interimanalyse, hvor der er nået statistisk signifikans.
See Table 28 for p-Value for inferential test of OS based on the pre-specified interim analysis, where statistical significance has been reached.
Median opfølgningstid på 10,1 måneder Median opfølgningstid på 52,8 måneder BICR-vurdering (blinded independent central review) i henhold til IWG (International Working Group)kriterierne, revideret i 2007, ud fra PET/CT-scanninger Baseret på patienter (n=145) med et respons ud fra uafhængig vurdering Baseret på patienter (n=18) med et respons ud fra uafhængig vurdering Baseret på Kaplan-Meier-estimering; inkluderer 31 patienter med respons på 6 måneder eller længere Baseret på Kaplan-Meier-estimering; inkluderer 9 patienter med respons på 6 måneder eller længere Baseret på Kaplan-Meier-estimering; inkluderer 7 patienter med respons på 12 måneder eller længere
Median follow-up time of 10.1 months Median follow-up time of 52.8 months Assessed by blinded independent central review according to the 2007 revised International Working Group (IWG) criteria by PET CT scans Based on patients (n=145) with a response by independent review Based on patients (n=18) with a response by independent review Based on Kaplan-Meier estimation; includes 31 patients with responses of 6 months or longer Based on Kaplan-Meier estimation; includes 9 patients with responses of 6 months or longer Based on Kaplan-Meier estimation; includes 7 patients with responses of 12 months or longer
Svære endokrinopatier, herunder binyrebarkinsufficiens, hypofysitis, type 1-diabetes mellitus, diabetisk ketoacidose, hypotyroidisme og hypertyroidisme er observeret i forbindelse med pembrolizumabbehandling.
Severe endocrinopathies, including adrenal insufficiency, hypophysitis, type 1 diabetes mellitus, diabetic ketoacidosis, hypothyroidism, and hyperthyroidism have been observed with pembrolizumab treatment.
Patienter med ECOG-performance-status ≥ 2 blev ekskluderet fra de kliniske studier med melanom, NSCLC, cHL og HNSCC (se pkt.
Patients with ECOG performance status score ≥ 2 were excluded from the clinical trials of melanoma, NSCLC, cHL, and HNSCC (see sections 4.4 and 5.1).
Ikke almindelig forhøjet amylase forhøjet bilirubin i blodet, forhøjet amylase forhøjet amylase
Uncommon amylase increased blood bilirubin increased, amylase increased amylase increased
* Baseret på den stratificerede Cox proportional hazard-model NR = Ikke nået
* Based on the stratified Cox proportional hazard model NR = not reached
PD-L1-positiv
PD-L1 positive
- Keytruda kan skade det ufødte barn eller øge risikoen for, at det dør.
- KEYTRUDA can cause harm or death to your unborn baby.
67% af patienterne havde M1-sygdom og størstedelen havde sygdom i stadie IV (stadie IV 32%, stadie IVa 14%, stadie IVb 4% og stadie IVc 44%).
Sixty-seven percent (67%) of patients had M1 disease and the majority had Stage IV disease (Stage IV 32%, Stage IVa 14%, Stage IVb 4%, and Stage IVc 44%).
HR* (98% CI) p-værdi (stratificeret log-rank) RFS ved måned 6 RFS-rate RFS ved måned 12 RFS-rate RFS ved måned 18 RFS-rate
Hazard ratio* (98% CI) p-Value (stratified log-rank) RFS at 6 months RFS rate RFS at 12 months RFS rate RFS at 18 months RFS rate
Se tabel 28 for p-værdien for inferentiel test af PFS baseret på den præspecificerede interimanalyse, hvor der er nået statistisk signifikans.
See Table 28 for p-Value for inferential test of PFS based on the pre-specified interim analysis, where statistical significance has been reached.
I tabel 4 opsummeres de centrale effektresultater efter den endelige analyse hos patienter, der tidligere har været behandlet med ipilimumab, og KaplanMeier-kurven for PFS er vist i figur 3.
Table 4 summarises key efficacy measures at the final analysis in patients previously treated with ipilimumab, and the KaplanMeier curve for PFS is shown in Figure 3.
Du kan også få kortikosteroider, før du får Keytruda i kombination med kemoterapi for at forebygge og/eller behandle kvalme, opkastning og andre bivirkninger forårsaget af kemoterapi.
Corticosteroids may also be given to you before receiving KEYTRUDA in combination with chemotherapy to prevent and/or treat nausea, vomiting, and other side effects caused by chemotherapy.
Sjælden myokarditis myokarditis k, perikarditis
Rare myocarditis myocarditis k, pericarditis
Ikke kendt afstødning af transplanterede solide organer
Uncommon sarcoidosis Not known solid organ transplant rejection
Forekomsten af bivirkninger af grad 3-5 var 76% for kombinationsbehandling med pembrolizumab og 71% for sunitinib alene.
Incidences of Grades 3-5 adverse reactions were 76% for pembrolizumab combination therapy and 71% for sunitinib alone.
• Tilsæt vandet ned langs siden af hætteglasset og ikke direkte ned i det frysetørrede pulver for at undgå skumdannelse.
• To avoid foaming, deliver the water along the walls of the vial and not directly on the lyophilised powder.
Hypotyroidisme gik over hos 153 (23,7%) patienter, 10 med sequelae.
Hypothyroidism resolved in 153 (23.7%) patients, 10 with sequelae.
L-histidin-hydrochloridmonohydrat Saccharose
L-histidine hydrochloride monohydrate Sucrose
Der findes ingen information vedrørende overdosering med pembrolizumab.
There is no information on overdose with pembrolizumab.
15% af patienterne havde sygdomsprogression efter tidligere platinbaseret neoadjuvant eller adjuvant kemoterapi.
Fifteen percent of patients had disease progression following prior platinumcontaining neoadjuvant or adjuvant chemotherapy.
* Cetuximab, platinbaseret behandling og 5-FU Baseret på den stratificerede Cox proportional hazard-model ‡ Respons: Bedste objektive respons, der er bekræftet komplet eller partielt respons
* Cetuximab, platinum, and 5-FU † Based on the stratified Cox proportional hazard model ‡ Response: Best objective response as confirmed complete response or partial response
Baseret på modellering og simulering af forholdet mellem dosis og eksponering med hensyn til pembrolizumabs virkning og sikkerhed er der ingen klinisk signifikant forskel i virkning eller sikkerhed blandt doserne på 200 mg hver 3. uge, 2 mg/kg hver 3. uge og 400 mg hver 6. uge som monoterapi (se pkt.
Based on the modelling and simulation of dose/exposure relationships for efficacy and safety for pembrolizumab, there are no clinically significant differences in efficacy or safety among the doses of 200 mg every 3 weeks, 2 mg/kg every 3 weeks, and 400 mg every 6 weeks as monotherapy (see section 4.2).
Thyroideafunktion og hormonniveauer skal monitoreres for at sikre passende hormonsubstitutionsbehandling.
Thyroid function and hormone levels should be monitored to ensure appropriate hormone replacement.
Patienter med EGFR- eller ALK-positive mutationer i tumor bør også have været i targeteret behandling inden behandling med KEYTRUDA.
Patients with EGFR or ALK positive tumour mutations should also have received targeted therapy before receiving KEYTRUDA.
De vigtigste resultatmål objektiv responsrate (ORR) og komplet remissionsrate (CRR) blev baseret på BICR (blinded independent central review)-vurdering i henhold til IWG (International Working Group)kriterierne revideret i 2007.
The major efficacy outcome measures (ORR and CRR) were assessed by blinded independent central review according to the 2007 revised International Working Group (IWG) criteria.
Hypofysefunktion og hormonniveauer skal monitoreres for at sikre passende hormonsubstitutionsbehandling.
Pituitary function and hormone levels should be monitored to ensure appropriate hormone replacement.
16% havde sygdomsprogression efter platinbaseret neoadjuverende eller adjuverende kemoterapi, og 84% havde tidligere fået 1-2 systemiske regimer for metastatisk sygdom.
Sixteen percent (16%) had disease progression following platinum-containing neoadjuvant or adjuvant chemotherapy, and 84% had received 1-2 prior systemic regimens for metastatic disease.
Fordelene ved behandling med pembrolizumab skal afvejes mod risikoen for mulig organafstødning hos disse patienter.
The benefit of treatment with pembrolizumab versus the risk of possible organ rejection should be considered in these patients.
Patienterne skal derfor monitoreres for ændringer i thyreoideafunktionen (ved behandlingsstart, periodevist i løbet af behandlingen og som indiceret på basis af den kliniske vurdering) samt for kliniske tegn og symptomer på thyreoideasygdomme.
Patients should be monitored for changes in thyroid function (at the start of treatment, periodically during treatment and as indicated based on clinical evaluation) and clinical signs and symptoms of thyroid disorders.
• Forpligtelse til at gennemføre foranstaltninger efter udstedelse af markedsføringstilladelse
Obligation to conduct post-authorisation measures
Komplikationer, inklusive graft versus host-sygdom (GVHD), hos personer der gennemgår knoglemarvstransplantation (stamcelletransplantation), hvor der anvendes stamceller fra en donor
Complications, including graft-versus-host-disease (GVHD), in people with bone marrow (stem cell) transplant that uses donor stem cells (allogeneic).
Keytruda gives til patienter, når de har fået foretaget en operation for at fjerne modermærkekræft for at forebygge, at deres kræft vender tilbage (adjuverende behandling).
People get KEYTRUDA after they have had surgery to remove melanoma to help prevent their cancer from coming back (adjuvant therapy).
Yderligere biomarkører, ud over PD-L1-ekspressionsstatus ved immunhistokemi (IHC) (f.eks. PD-L2, RNA-signatur osv.), der er prædiktive for pembrolizumabs virkning, skal undersøges sammen med yderligere information om mønstret for PD-L1-ekspression indhentet i igangværende NSCLC-studier (P001, P010, P024 og P042) og studier med urotelialt karcinom (KN045, KN052), HNSCC-studiet (KN040) og studiet med adjuverende behandling af resekteret stadie II-melanom (KN716):
Additional biomarkers other than PD-L1 expression status by Immunohistochemistry (IHC) (e.g. PD-L2, RNA signature, etc.) predictive of pembrolizumab efficacy should be investigated together with more information regarding the pattern of expression of PD-L1 obtained in the ongoing NSCLC studies (P001, P010, P024 and P042) and urothelial carcinoma studies (KN045, KN052), HNSCC study (KN040) and resected Stage II melanoma adjuvant study (KN716):
Klargøring og administration af infusionsvæske
Preparation and administration of the infusion
16% havde stadie IIIA; 46% havde stadie IIIB; 18% havde stadie IIIC (1-3 positive lymfeknuder), og 20% havde stadie IIIC (≥ 4 positive lymfeknuder); 50% var positive for BRAF V600-mutation og 44% var BRAF vildtype.
Sixteen percent had stage IIIA; 46% had stage IIIB; 18% had stage IIIC (1-3 positive lymph nodes) and 20% had stage IIIC (≥ 4 positive lymph nodes); 50% were BRAF V600 mutation positive and 44% were BRAF wild-type.
• Hvis ALAT eller ASAT er ≥ 3 gange ULN, men < 10 gange ULN uden samtidig total-bilirubinværdi ≥ 2 gange ULN, skal både KEYTRUDA og axitinib pauseres, indtil disse bivirkninger bedres til grad 0-1.
• If ALT or AST ≥ 3 times ULN but < 10 times ULN without concurrent total bilirubin ≥ 2 times ULN, both KEYTRUDA and axitinib should be withheld until these adverse reactions recover to Grades 0-1.
Antal (%) patienter med hændelse
Number (%) of patients with event
Levermetastaser med grad 2 forhøjelse af ASAT eller ALAT, hepatitis med ASAT- eller ALAT-stigning på ≥ 50% i forhold til baseline, og som varer ≥ 1 uge
In case of liver metastasis with baseline Grade 2 elevation of AST or ALT, hepatitis with AST or ALT increases ≥ 50% and lasts ≥ 1 week
Docetaxel 75 mg/m2 hver 3. uge
Docetaxel 75 mg/m2 every 3 weeks
4 ml koncentrat i et 10 ml klart hætteglas (type I-glas) med en coated grå chlorbutylprop og en aluminiumshætte med et mørkeblåt flip-off-låg, der indeholder 100 mg pembrolizumab.
4 mL of concentrate in a 10 mL Type I clear glass vial, with a coated grey chlorobutyl stopper and an aluminium seal with a dark blue coloured flip-off cap, containing 100 mg pembrolizumab.
90% af patienterne var behandlingsnaive, og 10% havde tidligere fået adjuvant eller neoadjuvant platinbaseret kemoterapi.
Ninety percent of patients were treatment naïve, and 10% received prior adjuvant or neoadjuvant platinum-based chemotherapy.
- Det er ukendt, om Keytruda udskilles i mælken hos mennesker.
- It is not known if KEYTRUDA passes into your breast milk.
Undersøgelser Meget almindelig forhøjet kreatinin i blodet forhøjet alaninaminotransferase, forhøjet aspartataminotransferase, forhøjet kreatinin i blodet
Investigations Very common blood creatinine increased alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased
På tidspunktet for denne analyse var HR i den samlede population (95% CI): 0,59 (0,45; 0,78) med 84/432 (19,4%) hændelser i armen med kombinationsbehandling og 122/429 (28,4%) hændelser i sunitinib-armen.
At the time of this analysis, the hazard ratio in the overall population (95% CI) was 0.59 (0.45, 0.78) with 84/432 (19.4%) events in the combination arm and 122/429 (28.4%) events in the sunitinib arm.
Der foreligger ingen data om pembrolizumabs mulige indvirkning på fertilitet.
No clinical data are available on the possible effects of pembrolizumab on fertility.
Begge behandlingsarme med pembrolizumab havde bedre (superior) PFS i forhold til kemoterapi, og der var ingen forskel mellem pembrolizumab-doserne.
Both pembrolizumab arms were superior to chemotherapy for PFS, and there was no difference between pembrolizumab doses.
Tabel 2: Bivirkninger hos patienter, som blev behandlet med pembrolizumab*
Table 2: Adverse reactions in patients treated with pembrolizumab*
Patienter, der fik placebo plus kemoterapi, som oplevede uafhængigt verificeret sygdomsprogression, blev tilbudt pembrolizumab som monoterapi.
Patients receiving placebo plus chemotherapy who experienced independently-verified progression of disease were offered pembrolizumab as monotherapy.
Studiet viste en statistisk signifikant forbedring i RFS for patienter randomiseret til armen med pembrolizumab sammenlignet med placebo ved den præspecificerede interimanalyse.
The trial demonstrated a statistically significant improvement in RFS for patients randomised to the pembrolizumab arm compared with placebo at the pre-specified interim analysis.
En opdateret OS-analyse blev udført, når patienterne havde en median opfølgingstid på 16,6 måneder (interval: 0,1 til 26,3 måneder).
An updated OS analysis was performed when patients had a median follow-up of 16.6 months (range: 0.1 to 26.3 months).
Thyreoideasygdomme, herunder hypotyroidisme, hypertyroidisme og tyroiditis, er rapporteret hos patienter, der fik pembrolizumab, og kan forekomme i hele behandlingsforløbet.
Thyroid disorders, including hypothyroidism, hyperthyroidism and thyroiditis, have been reported in patients receiving pembrolizumab and can occur at any time during treatment.
KEYNOTE-054: Placebokontrolleret studie med adjuverende behandling af patienter med komplet resekteret melanom
KEYNOTE-054: Placebo-controlled trial for the adjuvant treatment of patients with completely resected melanoma
Årsager til cisplatin-uegnethed var: creatininclearance på < 60 ml/min (50%) ved baseline, ECOG-performance-status på 2 (32%), ECOGperformance-status på 2 og creatinin-clearance på < 60 ml/min (9%) ved baseline og andre (hjertesvigt klasse III, perifer neuropati grad 2 eller højere og høretab grad 2 eller højere; 9%).
Reasons for cisplatin ineligibility included: baseline creatinine clearance of < 60 mL/min (50%), ECOG performance status of 2 (32%), ECOG performance status of 2 and baseline creatinine clearance of < 60 mL/min (9%), and other (Class III heart failure, Grade 2 or greater peripheral neuropathy, and Grade 2 or greater hearing loss; 9%).
85% af patienterne havde viscerale metastaser, herunder 21% med levermetastaser.
Eightyfive percent of patients had visceral metastases, including 21% with liver metastases.
Negativ for BRAF-mutation n=245
BRAF mutation negative n=245