natgillin/translations-raw huggingface dataset:
Sensitivitetsanalyser udført med den anbefalede dosis og behandlingsskema for Perjeta har dog vist, at der ved ekstreme værdier af disse to kovariater ikke er signifikant påvirkning af evnen til at opnå målet for steady-state koncentrationer i prækliniske tumorxenograft-modeller.
However sensitivity analyses performed at the recommended dose and schedule of Perjeta showed that at the extreme values of these two covariates, there was no significant impact on the ability to achieve target steady-state concentrations identified in preclinical tumour xenograft models.
Bivirkninger angives nedenfor i henhold til MedDRA-systemsorganklasser og med følgende frekvenskategorier:
The ADRs are listed below by MedDRA system organ class (SOC) and categories of frequency:
• Vil du få 840 mg Perjeta i løbet af 60 minutter.
You will be given 840 mg of Perjeta over 60 minutes.
Observationsperioden skal afsluttes inden efterfølgende infusion af trastuzumab eller kemoterapi (se pkt.
The observation period should be completed prior to any subsequent infusion of trastuzumab or chemotherapy (see section 4.4).
Patienter skal inden behandling have en venstre ventrikels ejektionsfraktion (LVEF) ≥ 50%.
Patients should have a pre-treatment left ventricular ejection fraction (LVEF) of ≥ 50%.
Den højere forekomst af febril neutropeni var hos de Perjeta-behandlede patienter associeret med den højere forekomst af mucositis og diarré hos disse patienter.
The higher incidence of febrile neutropenia in Perjeta-treated patients was associated with the higher incidence of mucositis and diarrhoea in these patients.
Sekundære endepunkter inkluderede vurdering af patient-rapporteret, overordnet helbredsstatus, dagligt fysisk funktionsniveau og behandlingssymptomer ved hjælp af EORTC QLQ-C30- og EORTC QLQ-BR23-spørgeskemaer.
Secondary endpoints included the assessment of patient-reported global health status, role and physical function, and treatment symptoms using the EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires.
Perjeta bør administreres af sundhedspersonale, der er uddannet til at behandle anafylaksi, samt på hospitalsafdelinger, hvor genoplivningsudstyr er umiddelbart tilgængeligt.
Perjeta should be administered by a healthcare professional prepared to manage anaphylaxis and in an environment where full resuscitation facilities are immediately available.
Hætteglasset må ikke rystes.
The vial must not be shaken.
Der var for få patienter med inflammatorisk brystkræft til at drage nogen klar konklusion, men pCR-raten var højere hos patienter, der fik Perjeta plus trastuzumab og docetaxel.
There were too few patients with inflammatory breast cancer to draw any firm conclusions but the pCR rate was higher in patients who received Perjeta plus trastuzumab and docetaxel.
Kaplan-Meier-kurve over samlet overlevelse
Figure 2 Kaplan-Meier Curve of Overall Survival
Ved administration sammen med Perjeta er anbefalingen for trastuzumab at følge en 3-ugers serie administreret som enten:
When administered with Perjeta the recommendation is to follow a 3 weekly schedule for trastuzumab administered as either:
• Tumorlyse syndrom (en tilstand, som kan forekomme, når kræftceller dør hurtigt, og forårsager ændringer i blodniveauer af mineraler og metabolitter måles i en blodprøve).
Tumour lysis syndrome (a condition which may happen when cancer cells die quickly, causing changes in blood levels of minerals and metabolites shown in a blood test).
På baggrund af de farmakologiske virkningsmekanismer for HER2-lægemidler og antracykliner, må risiko for kardiel toksicitet forventes at være højere ved samtidigt brug af Perjeta og antracykliner end ved sekventielt brug.
Based on the pharmacological actions of HER2-targeted agents and anthracyclines, the risk of cardiac toxicity might be expected to be higher with concomitant use of Perjeta and anthracyclines than with sequential use.
Studiets primære endepunkt var progressionsfri overlevelse vurderet af en uafhængig komite og defineret som tid fra randomiseringsdato til dato for sygdomsprogression eller død (af enhver årsag), såfremt døden indtrådte inden for 18 uger efter sidste tumorvurdering.
The primary endpoint of the study was progression-free survival (PFS) as assessed by an independent review facility (IRF) and defined as the time from the date of randomisation to the date of disease progression or death (from any cause) if the death occurred within 18 weeks of the last tumour assessment.
Behandling med Perjeta kan fremkalde svær diarré.
Treatment with Perjeta may cause severe diarrhoea.
Pertuzumabs farmakokinetik var i disse studier sammenlignelig med det, der var set i enkeltstof-studier.
The PK of pertuzumab in these studies was comparable to those observed in single-agent studies.
Fraværet af lægemiddelinteraktion blev bekræftet af farmakokinetiske data fra NEOSPHEREog APHINITY-studiet.
This absence of drug-drug interaction was confirmed by pharmacokinetic data from the NEOSPHERE and APHINITY studies.
Perjeta administreres som intravenøs infusion.
Perjeta is administered as an intravenous infusion.
Patienter, der behandles med Perjeta, skal have HER2-positiv-tumorstatus, defineret som en score på 3+ ved immunhistokemi (IHC) og/eller på > 2,0 ved in situ hybridisering (ISH) vurderet ved en valideret test.
Patients treated with Perjeta must have HER2-positive tumour status, defined as a score of 3+ by immunohistochemistry (IHC) and/or a ratio of ≥ 2.0 by in situ hybridisation (ISH) assessed by a validated test.
Ingen af patienterne oplevede anafylaktiske/overfølsomheds-reaktioner, som entydigt var relateret til de anti-terapeutiske antistoffer.
None of these patients experienced anaphylactic/hypersensitivity reactions that were clearly related to ADA.
Pertuzumab er et rekombinant humaniseret monoklonalt antistof specifikt rettet mod det ekstracellulære dimeriseringsdomæne (sub-domæne II) i det humane epidermale vækstfaktorreceptor 2-protein (HER2) og blokerer derved ligand-afhængig heterodimerisering af HER2 med andre HERfamiliemedlemmer, inklusive EGFR, HER3 og HER4.
Pertuzumab is a recombinant humanised monoclonal antibody that specifically targets the extracellular dimerization domain (subdomain II) of the human epidermal growth factor receptor 2 protein (HER2), and thereby, blocks ligand-dependent heterodimerisation of HER2 with other HER family members, including EGFR, HER3 and HER4.
Dosisjustering af pertuzumab er ikke nødvendig hos patienter med let eller moderat nedsat nyrefunktion.
Dose adjustments of pertuzumab are not needed in patients with mild or moderate renal impairment.
Metabolismen af pertuzumab er ikke umiddelbart undersøgt.
The metabolism of pertuzumab has not been directly studied.
De fleste af disse patienter havde tidligere fået antracyklinbehandling, 11% havde tidligere fået trastuzumab.
Most of these patients had received prior anthracycline therapy and 11% of all patients had received prior trastuzumab.
LVEF skal vurderes, inden behandling med Perjeta påbegyndes og i jævnlige intervaller under behandling med Perjeta (fx én gang under neoadjuverende behandling og hver 12. uge ved adjuverende eller metastatisk behandling) for at sikre, at LVEF ligger inden for normalområdet.
Assess LVEF prior to initiation of Perjeta and at regular intervals during treatment with Perjeta (e.g. once during neoadjuvant treatment and every 12 weeks in the adjuvant or metastatic setting) to ensure that LVEF is within normal limits.
4.2 og ikke er forbedret eller er faldet yderligere ved efterfølgende undersøgelser, skal seponering af Perjeta og trastuzumab kraftigt overvejes, medmindre fordelene for den enkelte patient vurderes at opveje risici.
If the LVEF has declined as indicated in section 4.2 and has not improved, or has declined further at the subsequent assessment, discontinuation of Perjeta and trastuzumab should be strongly considered, unless the benefits for the individual patient are deemed to outweigh the risks.
Det er derfor vigtigt at sikre sterilitet af den tilberedte infusionsvæske, og infusionsvæsken bør fremstilles af sundhedspersonale.
Therefore, care must be taken to ensure the sterility of the prepared solution for infusion and should be prepared by a healthcare professional.
• Medicinen gives i et drop i en vene (intravenøs infusion) hver tredje uge.
It is given by a drip into a vein (intravenous infusion) once every three weeks.
Se punkt 4 “Alvorlige bivirkninger” for mere information om, hvad du skal holde øje med under og efter infusionen.
See section 4 “Serious side effects” for more details about infusion reactions to look out for during the infusion and thereafter.
Perjeta og trastuzumab blev givet i standarddoser hver 3. uge.
Perjeta and trastuzumab were given at standard doses in a 3-weekly regimen.
BERENICE-studiets primære endepunkt er kardiologisk sikkerhed i den neoadjuverende behandlingsperiode.
The primary endpoint of the BERENICE trial is cardiac safety in the neoadjuvant period of the trial.
Effektresultater fra APHINITY-studiet opsummeres i tabel 5 og i figur 3.
The efficacy results from the APHINITY trial are summarised in Table 5 and in Figure 3.
Da Perjeta blev anvendt sammen med trastuzumab og kemoterapi i disse studier, er det svært at fastslå årsagssammenhæng mellem en bivirkning og det specifikke lægemiddel.
As Perjeta was used with trastuzumab and chemotherapy in these trials, it is difficult to ascertain the causal relationship of an adverse event to a particular medicinal product.
Tilsvarende resultater sås på tværs af præspecificerede patient-subgrupper, inklusive de subgrupper, der var stratificeret på baggrund af geografisk region og tidligere adjuverende/neoadjuverende behandling eller de novo metastatisk brystkræft (se figur 1).
Consistent results were observed across pre-specified patient subgroups including the subgroups based on stratification factors of geographic region and prior adjuvant/neoadjuvant therapy or de novo metastatic breast cancer (see Figure 1).
Efter operation fik alle patienter Perjeta og trastuzumab intravenøst hver 3. uge for at fuldføre 1 års behandling.
Following surgery all patients received Perjeta and trastuzumab intravenously every 3 weeks to complete 1 year of therapy.
På den første dag, hvor der kun blev administreret Perjeta, var den overordnede hyppighed af infusionsreaktioner 9,8% i placebo-gruppen og 13,2% i Perjeta-gruppen, og størstedelen af infusionsreaktionerne var lette eller moderate.
On the first day when only Perjeta was administered, the overall frequency of infusion reactions was 9.8% in the placebo-treated group and 13.2% in the Perjeta-treated group, with the majority of infusion reactions being mild or moderate.
Enkeltdoser over 25 mg/kg (1727 mg) er ikke afprøvet i kliniske studier.
In clinical trials, single doses higher than 25 mg/kg (1727 mg) have not been tested.
Der kan ikke gives dosisanbefalinger for patienter med svært nedsat nyrefunktion på grund af begrænsede farmakokinetiske data (se pkt.
No dose recommendations can be made for patients with severe renal impairment because of the limited pharmacokinetic data available (see section 5.2).
Der er ikke observeret forskelle i pertuzumabs farmakokinetik hos patienter med tidlig brystkræft sammenlignet med patienter med metastatisk brystkræft.
No differences in pertuzumab PK were observed in patients with early breast cancer compared to patients with metastatic breast cancer.
Febril neutropeni (lavt antal hvide blodlegemer med feber) Når Perjeta gives sammen med anden medicin mod kræft (trastuzumab og kemoterapi), kan antallet af hvide blodlegemer falde, og du kan få feber.
Febrile neutropenia (Low white blood cells with fever) When Perjeta is given with other cancer treatments (trastuzumab and chemotherapy), the number of white blood cells may drop and fever (raised temperature) may develop.
• Nedsat appetit
Reduced appetite
På tidspunktet for den primære analyse, var fordelene ved Perjeta mere åbenlyse i subgrupper af patienter med høj risiko for tilbagefald: patienter med lymfeknude-positiv eller hormonreceptornegativ sygdom (se tabel 6).
At the time of the primary analysis, the benefits of Perjeta were more apparent in subgroups of patients a high risk of recurrence: patients with node-positive or hormone receptor-negative disease (see table
Mens pertuzumab alene kan hæmme proliferationen af humane tumorceller, forstærker kombinationen af pertuzumab og trastuzumab i betydelig grad antitumor-aktiviteten i xenograft-modeller af HER2overekspression.
While pertuzumab alone inhibited the proliferation of human tumour cells, the combination of pertuzumab and trastuzumab significantly augmented antitumour activity in HER2-overexpressing xenograft models.
Studiets primære endepunkt var invasiv sygdomsfri overlevelse, defineret som tid fra randomisering til første forekomst af ipsilateral lokal eller regional invasiv brystkræft recidiv, fjernrecidiv, kontralateral invasiv brystkræft eller død af enhver årsag.
The primary endpoint of the study was invasive disease-free survival (IDFS), defined as the time from randomisation to first occurrence of ipsilateral local or regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, or death from any cause.
14 ml af Perjeta-koncentratet skal udtages fra hætteglasset og fortyndes i en 250 ml PVC- eller PVC-fri polyolefin-infusionspose med natriumchlorid 9 mg/ml (0,9%) infusionsvæske.
14 ml of Perjeta concentrate should be withdrawn from the vial and diluted into a 250 ml PVC or non-PVC polyolefin infusion bag of sodium chloride 9 mg/ml (0.9%) solution for infusion.
Neoadjuverende behandling
Neoadjuvant Treatment
Patienter, som tidligere er behandlet med antracykliner eller har fået strålebehandling af brystkassen, kan have øget risiko for LVEF-fald.
Patients who have received prior anthracyclines or prior radiotherapy to the chest area may be at higher risk of LVEF declines.
• Brug ikke Perjeta, hvis du bemærker partikler i infusionsvæsken, eller infusionsvæsken ikke har den rigtige farve (se punkt 6).
Do not use this medicine if you notice any particles in the liquid or it is the wrong colour (please see section 6).
I rammerne af neoadjuverende behandling vurderes lokalt avanceret og inflammatorisk brystkræft at indebære høj risiko, uafhængig af hormonreceptorstatus.
In the neoadjuvant setting, locally advanced and inflammatory breast cancers are considered as highrisk irrespective of hormone receptor status.
** Endelig analyse af samlet overlevelse, cut-off den 11. februar 2014.
** Final analysis of overall survival, cutoff date 11
Samlet set havde 6% af patienterne inflammatorisk brystkræft, 25% havde lokalt avanceret brystkræft, og 69% havde operabel brystkræft.
Overall 6% of patients had inflammatory breast cancer, 25% had locally advanced breast cancer and 69% had operable breast cancer.
Antal patienter unden hændelse efter tre år er udledt fra Kaplan-Meier-estimater.
3-year event-free rate derived from Kaplan-Meier estimates.
Perjetas sikkerhed er vurderet hos flere end 6000 patienter i fase I-, II- og III-studier hos patienter med forskellige former for malign sygdom og hovedsageligt behandlet med Perjeta i kombination med andre antineoplastiske midler.
The safety of Perjeta has been evaluated in more than 6,000 patients in Phase I, II, and III trials in patients with various malignancies and predominantly treated with Perjeta in combination with other antineoplastic agents.
Ved de efterfølgende infusioner vil du, hvis du godt kunne tåle den første infusion,
For all following infusions, if the first infusion was well tolerated:
Perjeta er beregnet til engangsbrug.
Perjeta is for single use only.
For dosisjustering af docetaxel og anden kemoterapi, se det relevante produktresumé.
For docetaxel and other chemotherapy dose modifications, see relevant SmPC.
Hvis der observeres partikler eller misfarvning, må infusionsvæsken ikke anvendes.
If particulates or discoloration are observed, the solution should not be used.
Studiets primære endepunkt var patologisk komplet respons rate (pCR-rate) i brystet (ypT0/is).
The primary endpoint of the study was pathological complete response (pCR) rate in the breast (ypT0/is).
Samlet set havde 7% af patienterne inflammatorisk brystkræft, 32% havde lokalt avanceret brystkræft, og 61% havde operable brystkræft.
Overall 7% of patients had inflammatory breast cancer, 32% had locally advanced breast cancer and 61% had operable breast cancer.
Hvis du har inflammation (en betændelseslignende tilstand) i fordøjelseskanalen (fx mundbetændelse eller diarré), vil du måske have større risiko for at udvikle denne bivirkning.
If you have inflammation of the digestive tract (e.g.sore mouth or diarrhoea) you may be more likely to develop this side effect.
pCR-raterne var sammenlignelige hos patienter med operabel og lokalt avanceret sygdom.
pCR rates were similar in patients with operable and locally advanced disease.
Efter operation fik alle patienter trastuzumab for at fuldføre 1 års behandling.
Following surgery all patients received trastuzumab to complete one year of therapy.
Som resultat heraf hæmmer pertuzumabligand-initierede intracellullære signalprocesser gennem to vigtige signalveje, mitogen-aktiveret protein-kinase og fosfoinositid 3-kinase.
As a result, pertuzumab inhibits ligand-initiated intracellular signalling through two major signal pathways, mitogen-activated protein (MAP) kinase and phosphoinositide 3-kinase (PI3K).
Perjetas sikkerhed og virkning er ikke undersøgt hos børn og unge < 18 år.
The safety and efficacy of Perjeta in children and adolescents below 18 years of age have not been established.
Adjuverende behandling
Adjuvant Treatment
Den populationsfarmakokinetiske analyse tydede ikke på forskelle i farmakokinetikken på baggrund af alder, køn eller etnicitet (japanske patienter vs. ikke-japanske).
The population PK analysis suggested no PK differences based on age, gender and ethnicity (Japanese versus non-Japanese).
• CLEOPATRA, hvor Perjeta blev givet i kombination med docetaxel og trastuzumab til patienter med metastatisk brystkræft (n=453)
• CLEOPATRA, in which Perjeta was given in combination with docetaxel and trastuzumab to patients with metastatic breast cancer (n=453)
Patienter med metastaser, bilateral brystkræft, klinisk signifikante kardielle risikofaktorer (se pkt.
Patients with metastases, bilateral breast cancer, clinically important cardiac risk factors
pCR-raten var lavere i subgruppen af patienter med hormonreceptor-positive tumorer (interval 46,2% til 50,0%) end hos patienter med hormonreceptor-negative tumorer (interval 65,0% til 83,8%).
The pCR rates were lower in the subgroup of patients with hormone receptor positive tumours (range 46.2% to 50.0%) than in patients with hormone receptor-negative tumours (range 65.0% to 83.8%).
Hvis et carboplatin-baseret regime anvendes, er den anbefalede dosis af docetaxel 75 mg/m2 gennem hele forløbet (ingen optrapning af dosis).
If a carboplatin-based regimen is used, the recommended dose for docetaxel is 75 mg/m2 throughout (no dose escalation).
• Hvis du nogensinde har haft hjerteproblemer (som for eksempel hjertesvigt, behandlingskrævende meget uregelmæssig hjerterytme, ukontrolleret forhøjet blodtryk, nyligt hjertetilfælde), vil din hjertefunktion derfor blive kontrolleret før og under behandlingen med Perjeta, og din læge vil lave undersøgelser for at kontrollere, om dit hjerte virker, som det skal.
Talk to your doctor or nurse before you are given Perjeta: If you have ever had heart problems (such as heart failure, treatment for serious irregular heartbeats, uncontrolled high blood pressure, recent heart attack), your heart function will be checked before and during treatment with Perjeta and your doctor will run tests to check if your heart is working properly.
Infusionshastigheden kan reduceres eller infusionen afbrydes, hvis patienten udvikler en infusionsreaktion (se pkt.
The infusion rate may be slowed or interrupted if the patient develops an infusion reaction (see section 4.8).
I tabel 2 opsummeres bivirkninger fra de Perjeta-behandlede grupper i følgende pivotale kliniske studier:
Table 2 summarizes the ADRs from the Perjeta-treated groups of the following pivotal clinical trials:
Hvis du oplever en eller flere af ovennævnte bivirkninger, efter behandlingen med Perjeta er stoppet, skal du straks kontakte lægen og fortælle, at du tidligere har været i behandling med Perjeta.
If you experience any of the above symptoms after treatment with Perjeta has been stopped, you should consult your doctor immediately and inform him or her that you have previously been treated with Perjeta.
Dosis på 420 mg pertuzumab administreres så hurtigt som muligt.
The 420 mg dose of pertuzumab should be administered as soon as possible.
Patienter med klinisk signifikante kardiale risikofaktorer blev ikke inkluderet (se pkt.
Patients with clinically important cardiac risk factors were not included (see section 4.4).
• Betændelse i neglevolden, der hvor negl og hud mødes • Tilstand, hvor det venstre hjertekammers funktion er nedsat, med eller uden symptomer
Inflammation of the nail bed where the nail and skin meet Condition in which the left ventricle of the heart is functionally impaired with or without symptoms
Størstedelen af hændelserne var af grad 1 eller 2.
The majority of rash events were Grade 1 or 2.
17 ENTYDIG IDENTIFIKATOR - 2D-STREGKODE <Der er anført en 2D-stregkode, som indeholder en entydig identifikator.>
UNIQUE IDENTIFIER - 2D BARCODE 2D barcode carrying the unique identifier included.
Behandling med Perjeta og trastuzumab kan genoptages, hvis LVEF stiger til > 45% eller til 40-45% i forbindelse med en forskel på < 10% point under værdierne inden behandling.
Perjeta and trastuzumab may be resumed if the LVEF has recovered to > 45%, or to 40-45% associated with a difference of < 10% points below pre-treatment values.
Patienter, som ansås for at egne sig til neoadjuverende behandling med trastuzumab plus antracyklin/taxan-baseret kemoterapi blev tildelt et af de to følgende regimer før operation:
Patients considered suitable for neoadjuvant treatment with trastuzumab plus anthracycline/taxane-based chemotherapy were allocated to receive one of the two following regimens prior to surgery as follows:
Hvis du får en alvorlig bivirkning, kan lægen vælge at stoppe behandling med Perjeta.
If you get any serious reaction, your doctor may stop treatment with Perjeta.
Effektresultaterne er vist i tabel 4.
The efficacy results are presented in Table 4.
Behandling med Perjeta og trastuzumab bør afbrydes i mindst 3 uger ved symptomer, der tyder på kongestiv hjerteinsufficiens.
Perjeta and trastuzumab should be withheld for at least 3 weeks for any signs and symptoms suggestive of congestive heart failure.
Symptomer kan inkludere nyreproblemer (svaghed, åndenød, træthed og forvirring), hjerteproblemer (flakkende hjerte med et hurtigere eller langsommere hjerteslag), anfald, opkastning eller diarré og snurren i mund, hænder eller fødder.
Symptoms may include kidney problems (weakness, shortness of breath, fatigue and confusion), heart problems (fluttering of the heart of a faster or slower heartbeat), seizures, vomiting or diarrhoea and tingling in the mouth, hands or feet
• 6 serier af docetaxel i kombination med carboplatin
• 6 cycles of docetaxel in combination with carboplatin
Kvinder i den fertile alder skal bruge sikker prævention, mens de er i behandling med Perjeta og i 6 måneder efter den sidste dosis af pertuzumab.
Women of childbearing potential should use effective contraception while receiving Perjeta and for 6 months following the last dose of pertuzumab.
Se punkt 4 ”Alvorlige bivirkninger” for yderligere information om, hvad du skal holde øje med.
See section 4 “Serious side effects” for more details about signs of heart problems to look out for.
Da patienter med hjernemetastaser blev udelukket fra studiet, er der ingen data for Perjetas aktivitet på hjernemetastaser.
Due to the exclusion of patients with brain metastases no data are available on Perjeta activity on brain metastases.