natgillin/translations-raw huggingface dataset:
I BCIRG 006-studiet havde 213/1075 patienter i DCarbH (TCH)-armen, 221/1074 patienter i AC→DH (AC→TH)-armen og 217/1073 patienter i AC→D (AC→T)-armen en Karnofsky performance status ≤ 90 (enten 80 eller 90). 
In study BCIRG 006, 213/1075 patients in the DCarbH (TCH) arm, 221/1074 patients in the AC→DH (AC→TH) arm, and 217/1073 in the AC→D (AC→T) arm had a Karnofsky performance status ≤ 90 (either 80 or 90).
Data fra studie JP16003, et enkelt-arm-studie med trastuzumab (4 mg/kg intravenøs støddosis og 2 mg/kg intravenøst ugentligt) og docetaxel (60 mg/m2 intravenøst) hos japanske kvinder med HER2 
Data from study JP16003, a single-arm study of trastuzumab (4 mg/kg intravenous loading dose and 2 mg/kg intravenous weekly) and docetaxel (60 mg/m2 intravenous) in Japanese women with HER2
Palmoplantart erythrodysæstesisyndrom 
Palmar-plantar erythrodysaesthesia syndrome
Primær tumortype N 
Primary tumor type N
Hvert hætteglas indeholder enten: o 150 mg trastuzumab, som skal opløses i 7,2 ml vand til injektionsvæsker, eller o 420 mg trastuzumab, som skal opløses i 20 ml vand til injektionsvæsker. 
Each vial contains either; o 150 mg trastuzumab that has to be dissolved in 7.2 mL of water for injections, or o 420 mg trastuzumab that has to be dissolved in 20 mL of water for injections.
• ændret smagssans 
• altered taste
Regimen Primær tumortype 
Regimen Primary tumor type
I det pivotale studie med docetaxel (100 mg/m2 
In the pivotal trial of docetaxel (100 mg/m2 infused over
I studiet ToGA (BO18255) blev patienter med tumorer, som enten var IHC3+ eller FISH-positive, defineret som HER2-positive og dermed inkluderet i studiet. 
In the ToGA (BO18255) trial, patients whose tumours were either IHC3+ or FISH positive were defined as HER2 positive and thus included in the trial.
Studie WO16229: støddosis 8 mg/kg efterfulgt af 6 mg/kg med 3-ugers intervaller Studie MO16982: støddosis 6 mg/kg ugentligt x 3 efterfulgt af 6 mg/kg med 3-ugers intervaller Studie BO15935 
Study WO16229: loading dose 8 mg/kg, followed by 6 mg/kg 3 weekly schedule Study MO16982: loading dose 6 mg/kg weekly x 3; followed by 6 mg/kg 3-weekly schedule Study BO15935
Post-hoc eksplorativ analyse med sygdomsfri overlevelse og symptomatiske kardielle hændelser 
Post-hoc exploratory analysis with DFS and symptomatic cardiac events
Hvis du får Ogivri i kombination med kemoterapi, kan nogle af bivirkningerne skyldes kemoterapien. 
If you receive Ogivri in combination with chemotherapy, some of them may also be due to the chemotherapy.
Komplet instruktion i udførelse af analyserne og fortolkning af resultaterne bør hentes fra produktinformationen leveret med de anvendte HER2-forsøgsanalyser. 
Full instructions on assay performance and results interpretation should be taken from the product information leaflet provided with the HER2 testing assays used.
• leverskade/-svigt 
• liver damage/failure
Det Europæiske Lægemiddelagentur har dispenseret fra kravet om at fremlægge resultaterne af studier med referencelægemidlet, som indeholder trastuzumab, i alle undergrupper af den pædiatriske population ved bryst- og ventrikelkræft (se pkt. 
The European Medicines Agency has waived the obligation to submit the results of studies with the reference medicinal product containing trastuzumab in all subsets of the paediatric population for breast and gastric cancer (see section 4.2 for information on paediatric use).
Ogivri kan ordineres i kombination med kemoterapilægemidlerne paclitaxel og docetaxel som første behandling for metastatisk brystkræft, eller det kan ordineres alene, hvis andre behandlinger har vist sig ikke at virke. 
Ogivri may be prescribed in combination with the chemotherapy medicine paclitaxel or docetaxel as first treatment for metastatic breast cancer or it may be prescribed alone if other treatments have proved unsuccessful.
De inkluderer svækkelse af hjertemusklen, der muligvis kan føre til hjertesvigt, betændelse (hævet, rød, varm og med smerter) i hinden omkring hjertet og forstyrrelser i hjerterytmen. 
They include weakening of the heart muscle possibly leading to heart failure, inflammation (swollen, red, hot, and in pain) of the lining around the heart and heart rhythm disturbances.
Generelt anses FISH for at være positiv, hvis forholdet mellem antallet af kopier af HER2-genet per tumorcelle relativt til antallet af kromosom 17-kopier er større end eller lig med 2, eller hvis der er flere end 4 kopier af HER2-genet per tumorcelle, såfremt der ikke anvendes kromosom 17-kontrol. 
In general, FISH is considered positive if the ratio of the HER2 gene copy number per tumour cell to the chromosome 17 copy number is greater than or equal to 2, or if there are more than 4 copies of the HER2 gene per tumour cell if no chromosome 17 control is used.
Hvis venstre ventrikel ejektionsfraktions (LVEF)-procent falder ≥ 10 point fra baseline OG til under 50 %, skal behandlingen afbrydes, og LVEF-vurdering gentages inden for ca. 3 uger. 
If left ventricular ejection fraction (LVEF) percentage drops ≥ 10 points from baseline AND to below 50 %, treatment should be suspended and a repeat LVEF assessment performed within approximately 3 weeks.
I et af de 3 pivotale studier, hvor en median opfølgningstid på 5,5 år var tilgængelig (BCIRG 006), blev der observeret en kontinuerlig stigning i det samlede antal af symptomatiske kardielle hændelser eller LVEF-hændelser hos patienter, som fik trastuzumab administreret samtidig med et taxan efter antracyklinbehandling, på op til 2,37 %, sammenlignet med ca. 1 % i de to komparatorarme (antracyklin plus cyclophosphamid efterfulgt af taxan og taxan, carboplatin og trastuzumab). 
In one of the 3 pivotal studies conducted in which a median follow-up of 5.5 years was available (BCIRG006) a continuous increase in the cumulative rate of symptomatic cardiac or LVEF events was observed in patients who were administered trastuzumab concurrently with a taxane following anthracycline therapy up to 2.37 % compared to approximately 1 % in the two comparator arms (anthracycline plus cyclophosphamide followed by taxane and taxane, carboplatin and trastuzumab).
Samlet CL-interval fra Cmax,ss til Cmin,ss (l/dag) 
Total CL range from Cmax,ss to Cmin,ss (L/day)
Risikoen for kardiel dysfunktion hos patienter, der fik trastuzumab efter afsluttet adjuverende kemoterapi, var associeret med en højere kumulativ antracyklin-dosis, givet før initiering af trastuzumab, og et body mass index (BMI) > 25 kg/m2. 
In patients receiving trastuzumab after completion of adjuvant chemotherapy, the risk of cardiac dysfunction was associated with a higher cumulative dose of anthracycline given prior to initiation of trastuzumab and a body mass index (BMI) > 25 kg/m2.
Neoplasma-progression 
Neoplasm progression
Som følge heraf har trastuzumab, både i in vitro-analyser og på dyr, vist sig at hæmme proliferationen af humane tumorceller med overekspression af HER2. 
As a result, trastuzumab has been shown, in both in vitro assays and in animals, to inhibit the proliferation of human tumour cells that overexpress HER2.
Denne testanalyse, som blev udført af et centrallaboratorium, fra de kliniske studier benyttede en skala fra 0 til 3+. 
This investigative clinical trial assay performed in a central laboratory utilised a 0 to 3+ scale.
AUCss, 0-21dage (µg.dag/ml) 
AUCss, 0-21days (mcg.day/mL)
Kontakt lægen, apotekspersonalet eller sundhedspersonalet, før du får Ogivri, hvis: 
Talk to your doctor, pharmacist or nurse before you are given Ogivri if:
Der er ingen tilgængelige resultater, der sammenligner virkningen af trastuzumab , administreret med kemoterapi i den adjuverende behandling, med virkningen i den neoadjuverende-adjuverende behandling. 
So far, no results are available which compare the efficacy of trastuzumab administered with chemotherapy in the adjuvant setting with that obtained in the neo-adjuvant/adjuvant setting.
MARKEDSFØRINGSTILLADELSESNUMMER (-NUMRE) EU/1/18/1341/002 
MARKETING AUTHORISATION NUMBER(S) EU/1/18/1341/002
En endelig analyse blev udført efter en median opfølgning på 8 år, hvilket viste, at 1 års trastuzumabbehandling er associeret med 24 % risikoreduktion sammenlignet med observation alene (risikoforhold = 0,76; 95 % konfidensinterval 0,67-0,86). 
A final analysis was performed after a median follow-up of 8 years, which showed that 1 year trastuzumab treatment is associated with a 24 % risk reduction compared to observation only (HR = 0.76, 95 % CI 0.67, 0.86).
Hvis patienten undlader en dosis af trastuzumab i mere end en uge, bør der administreres en ny støddosis af trastuzumab over ca. 90 minutter (ugentligt doseringsregime: 4 mg/kg; 3-ugers doseringsregime: 8 mg/kg) så hurtigt som muligt. 
If the patient has missed a dose of trastuzumab by more than one week, a re-loading dose of trastuzumab should be administered over approximately 90 minutes (weekly regimen: 4 mg/kg; threeweekly regimen: 8 mg/kg) as soon as possible.
Ogivri er indiceret til behandling af voksne patienter med HER2-positiv metastatisk brystkræft: - som enkeltstofbehandling til behandling af de patienter, som har fået mindst to kemoterapiregimer for deres metastatiske sygdom. 
Ogivri is indicated for the treatment of adult patients with HER2 positive metastatic breast cancer (MBC): - as monotherapy for the treatment of those patients who have received at least two chemotherapy regimens for their metastatic disease.
Efterfølgende vedligeholdelsesdoser af trastuzumab (henholdsvis ugentligt doseringsregime: 2 mg/kg; 3-ugers doseringsregime: 6 mg/kg) bør administreres 7 eller 21 dage senere i henhold til henholdsvis ugentlige eller 3-ugers doseringsregimer. 
Subsequent trastuzumab maintenance doses (weekly regimen: 2 mg/kg; three-weekly regimen 6 mg/kg respectively) should be administered 7 days or 21 days later according to the weekly or three-weekly schedules respectively.
2 kohorter (én anvendte subkutan formulering i hætteglas og én anvendte subkutan formulering i injektionssystem) blev i dette studie undersøgt ved et 2-arms overkrydsningsdesign, hvor 488 patienter blev randomiseret til ét af to forskellige 3-ugers behandlingsforløb med trastuzumab (intravenøs [serie 1-4] → subkutan [serie 5-8] eller subkutan [serie 1-4] → intravenøs [serie 5-8]). 
In this trial, 2 cohorts (one using subcutaneous formulation in vial and one using subcutaneous formulation in administration system) were investigated using a 2-arm, cross-over design with 488 patients being randomized to one of two different three-weekly Trastuzumab treatment sequences (intravenous [Cycles 1-4]→ subcutaneous [Cycles 5-8], or subcutaneous [Cycles 1-4]→ intravenous [Cycles 5-8]).
Ved et fald i LVEF-procenten på ≥ 10 point fra baseline OG til under 50 % bør behandlingen afbrydes, og en ny LVEF-måling udføres inden for ca. 3 uger. 
If LVEF percentage drops ≥ 10 points from baseline AND to below 50%, treatment should be suspended and a repeat LVEF assessment performed within approximately 3 weeks.
Patienter med tidlig brystkræft bør behandles med trastuzumab i 1 år, eller indtil sygdommen recidiverer afhængigt af, hvad der forekommer først; forlængelse af behandling af tidlig brystkræft udover et år anbefales ikke (se pkt. 
Patients with EBC should be treated with trastuzumab for 1 year or until disease recurrence, whichever occurs first; extending treatment in EBC beyond one year is not recommended (see section 5.1).
Patienter med metastatisk brystkræft og tidlig brystkræft havde sammenlignelige farmakokinetiske parametre (f.eks. clearance, distributionsvolumen for det centrale kompartment (Vc)) og populationsforudsagte steady-state eksponeringer (Cmin, Cmax og AUC). 
MBC and EBC patients had similar PK parameters (e.g. clearance (CL), the central compartment volume (Vc)) and population-predicted steady-state exposures (Cmin, Cmax and AUC).
Alle kandidater til behandling med trastuzumab, men specielt de som tidligere har fået antracykliner og cyclophosphamid (AC), skal have foretaget en kardiel vurdering ved baseline, inklusive anamnese og objektiv undersøgelse, elektrokardiogram (ekg), ekkokardiografi, og/eller MUGA-scanning eller magnetisk resonansscanning. 
All candidates for treatment with trastuzumab, but especially those with prior anthracycline and cyclophosphamide (AC) exposure, should undergo baseline cardiac assessment including history and physical examination, electrocardiogram (ECG), echocardiogram, and/or multigated acquisition (MUGA) scan or magnetic resonance imaging.
I den neoadjuverende-adjuverende behandling var studie MO16432, et randomiseret multicenterstudie, designet til at undersøge den kliniske virkning af samtidig administration af trastuzumab og neoadjuverende kemoterapi inkluderende både et antracyklin og et taxan, efterfulgt af adjuverende trastuzumab op til en total behandlingsvarighed på 1 år. 
In the neoadjuvant-adjuvant treatment setting, study MO16432, a multicentre randomised trial, was designed to investigate the clinical efficacy of concurrent administration of trastuzumab with neoadjuvant chemotherapy including both an anthracycline and a taxane, followed by adjuvant trastuzumab, up to a total treatment duration of 1 year.
- Øvrige indholdsstoffer: L-histidinhydrochlorid, L-histidin, sorbitol (se afsnit 2 “Ogivri indeholder sorbitol”), Macrogol 3350, saltsyre og natriumhydroxid (til justering af pH). 
- The other ingredient(s) are L-histidine hydrochloride, L-histidine, Sorbitol (see section 2 “Ogivri contains sorbitol”), Macrogol 3350, Hydrochloric acid and Sodium hydroxide (for pH adjustment).
- i kombination med neoadjuverende kemoterapi efterfulgt af adjuverende Ogivri-behandling for lokalt avanceret (herunder inflammatorisk) sygdom eller tumorer > 2 cm i diameter (se pkt. 
- in combination with neoadjuvant chemotherapy followed by adjuvant Ogivri therapy, for locally advanced (including inflammatory) disease or tumours > 2 cm in diameter (see sections 4.4 and
Administration i kombination med paclitaxel eller docetaxel I de pivotale studier (H0648g, M77001) blev paclitaxel eller docetaxel administreret dagen efter den første dosis trastuzumab (se dosis i produktresuméet for paclitaxel eller docetaxel) og umiddelbart efter administrationen af de efterfølgende doser af trastuzumab, hvis den forudgående dosis trastuzumab var veltolereret. 
Administration in combination with paclitaxel or docetaxel In the pivotal trials (H0648g, M77001), paclitaxel or docetaxel was administered the day following the first dose of trastuzumab (for dose, see the Summary of Product Characteristics (SmPC) for paclitaxel or docetaxel) and immediately after the subsequent doses of trastuzumab if the preceding dose of trastuzumab was well tolerated.
For at forebygge fejlmedicinering er det vigtigt at kontrollere hætteglassets etiket for at sikre, at det lægemiddel, der klargøres og administreres, er trastuzumab og ikke trastuzumabemtansin. 
In order to prevent medication errors it is important to check the vial labels to ensure that the medicinal product being prepared and administered is trastuzumab and not trastuzumab emtansine.
• hæmorider (hævede blodkar rundt om endetarmen) 
• haemorrhoids (swelling of blood vessels around the back passage)
Det kan tage op til 7 måneder at udskille Ogivri fra organismen. 
It may take up to 7 months for Ogivri to be removed from the body.
Kun til intravenøs anvendelse 
For IV use only
I 3 pivotale kliniske studier, hvor adjuverende trastuzumab blev administreret i kombination med kemoterapi, var hyppigheden af kardiel dysfunktion af grad 3/4 (især symptomatisk kongestiv hjerteinsufficiens) tilsvarende hos patienter, der fik administreret kemoterapi alene (dvs. som ikke fik trastuzumab), som hos patienter, der fik trastuzumab sekventielt efter et taxan (0,3-0,4 %). 
In 3 pivotal clinical trials of adjuvant trastuzumab given in combination with chemotherapy, the incidence of grade 3/4 cardiac dysfunction (specifically symptomatic Congestive Heart Failure) was similar in patients who were administered chemotherapy alone (i.e. did not receive trastuzumab) and in patients who were administered trastuzumab sequentially after a taxane (0.3-0.4 %).
• Overfølsomhed over for det aktive stof, murine proteiner, eller over for et eller flere af hjælpestofferne anført i pkt. 
• Hypersensitivity to the active substance, murine proteins, or to any of the excipients listed in section 6.1.
6.6 for instruktioner om rekonstitution af lægemidlet før administration. 
For instructions on reconstitution of the medicinal product before administration, see section 6.6.
Patienter med metastatisk brystkræft, som tidligere har fået antracykliner, har også risiko for at udvikle kardiel dysfunktion ved trastuzumab-behandling, selvom risikoen er lavere end ved samtidig brug af trastuzumab og antracykliner. 
Patients with MBC who have previously received anthracyclines are also at risk of cardiac dysfunction with trastuzumab treatment, although the risk is lower than with concurrent use of trastuzumab and anthracyclines.
Trastuzumab blev undersøgt som adjuverende behandling i 4 store randomiserede multicenterstudier: 
In the adjuvant treatment setting, trastuzumab was investigated in 4 large multicentre, randomised, trials.
Kombinationsbehandling med trastuzumab og anastrozol Trastuzumab er blevet undersøgt i kombination med anastrozol ved 1. linjebehandling af metastatisk brystkræft hos hormon-receptor-positive (dvs. østrogen-receptor og/eller progesteron-receptor) postmenopausale patienter med overekspression af HER2. 
Combination treatment with Trastuzumab and anastrozole Trastuzumab has been studied in combination with anastrozole for first line treatment of MBC in HER2 overexpressing, hormone-receptor (i.e. estrogen-receptor (ER) and/or progesterone-receptor (PR)) positive postmenopausal patients.
Når infusionsvæsken er klargjort, skal den indgives med det samme. 
Once the infusion is prepared it should be administered immediately.
I et efterfølgende studie med prospektiv monitorering af hjertefunktionen var incidensen af symptomatisk kongestiv hjerteinsufficiens 2,2 % hos patienter, der fik trastuzumab og docetaxel, sammenlignet med 0 % hos patienter, der fik doxetaxel alene. 
In a subsequent trial with prospective monitoring of cardiac function, the incidence of symptomatic CHF was 2.2 % in patients receiving trastuzumab and docetaxel, compared with 0 % in patients receiving docetaxel alone.
Paclitaxel i kombination med trastuzumab blev administreret som følger: - intravenøs paclitaxel - 80 mg/m2 som kontinuerlig intravenøs infusion, administreret hver uge i 12 
Paclitaxel, in combination with trastuzumab, was administered as follows: - intravenous paclitaxel - 80 mg/ m2 as a continuous intravenous infusion, given every week for
- Studie BO16348 var designet til at sammenligne 1 og 2 års trastuzumab-behandling hver 3. uge versus observation hos patienter med HER2-positiv tidlig brystkræft efter operation, standardkemoterapi og strålebehandling (hvis indiceret). 
- Study BO16348 was designed to compare one and two years of three-weekly trastuzumab treatment versus observation in patients with HER2 positive EBC following surgery, established chemotherapy and radiotherapy (if applicable).
• væskeophobning (hævelser) i ben eller arme, 
• fluid retention (swelling) in the legs or arms,
Den testmetode for overekspression af HER2, som blev brugt til at bestemme patienternes egnethed i det pivotale studie med trastuzumab-monoterapi og i de kliniske studier med trastuzumab plus paclitaxel, anvendte immunhistokemisk farvning for HER2 af fikseret materiale fra brysttumorer ved hjælp af de murine monoklonale antistoffer CB11 og 4D5. 
The test method for HER2 overexpression used to determine eligibility of patients in the pivotal trastuzumab monotherapy and trastuzumab plus paclitaxel clinical trials employed immunehistochemical staining for HER2 of fixed material from breast tumours using the murine monoclonal antibodies CB11 and 4D5.
Opløsninger af Ogivri til intravenøs infusion er fysisk og kemisk stabile i polyvinylchlorid-, polyethylen- eller polypropylenposer, som indeholder natriumchlorid 9 mg/ml (0,9 %) injektionsvæske, opløsning, i 24 timer ved temperaturer, som ikke overstiger 30 °C. 
Solutions of Ogivri for intravenous infusion are physically and chemically stable in polyvinylchloride, polyethylene or polypropylene bags containing sodium chloride 9 mg/mL (0.9 %) solution for injection for 24 hours at temperatures not exceeding 30°C.
I det neoadjuverende-adjuverende studie af tidlig brystkræft (BO22227) udviklede 10,1 % (30/296) af patienterne behandlet med intravenøst trastuzumab antistoffer mod trastuzumab ved en median opfølgningstid på mere end 70 måneder. 
In the neoadjuvant-adjuvant EBC study (BO22227), at a median follow-up exceeding 70 months, 10.1 % (30/296) of patients treated with trastuzumab intravenous developed antibodies against trastuzumab.
Ogivri er et pulver til koncentrat til intravenøs infusionsvæske, opløsning, som leveres i et hætteglas med en gummiprop og indeholder enten 150 mg eller 420 mg trastuzumab. 
Ogivri is a powder for concentrate for solution for intravenous infusion, which is supplied in a glass vial with a rubber stopper containing either 150 mg or 420 mg of trastuzumab.
Hos patienter med tidlig brystkræft, som er egnede til neoadjuverende-adjuverende behandling, bør trastuzumab kun bruges samtidig med antracykliner hos kemoterapi-naive patienter og kun i regimer med lave antracyklindoser dvs. maksimale kumulative doser af doxorubicin 180 mg/m2 eller epirubicin 360 mg/m2. 
In patients with EBC eligible for neoadjuvant-adjuvant treatment, trastuzumab should be used concurrently with anthracyclines only in chemotherapy-naive patients and only with low-dose anthracycline regimens i.e. maximum cumulative doses of doxorubicin 180 mg/m2 or epirubicin
Behandling med AC→PH resulterede i en statistisk signifikant forbedring af samlet overlevelse sammenlignet med AC→P (stratificeret risikoforhold = 0,64; 95 % konfidensinterval = 0,55-0,74; log-rank p-værdi < 0,0001). 
Treatment with AC→PH resulted in a statistically significant improvement in OS compared with AC→P (stratified HR = 0.64; 95% CI [0.55, 0.74]; log-rank p-value < 0.0001).
3-ugers doseringsregime ved metastatisk brystkræft Effektresultaterne fra ikke-komparative studier med monoterapi og kombinationsterapi er sammenfattet i tabel 5: 
Three -weekly dosing in metastatic breast cancer The efficacy results from the non-comparative monotherapy and combination therapy studies are summarised in Table 5:
Trastuzumab er også blevet anvendt i kombination med paclitaxel eller docetaxel til behandling af patienter, som endnu ikke har fået kemoterapi for deres metastatiske sygdom. 
Trastuzumab has also been used in combination with paclitaxel or docetaxel for the treatment of patients who have not received chemotherapy for their metastatic disease.
I den samlede analyse af NSABP B-31- og NCCTG N9831-studierne var tidlig brystkræft begrænset til kvinder med operabel brystkræft med høj risiko, defineret som HER2-positiv og med positive lymfeknuder i aksillen eller HER2-positiv og med negative lymfeknuder i aksillen med høje risikofaktorer (tumorstørrelse > 1 cm og ER-negativ eller tumorstørrelse > 2 cm, uanset hormonstatus). 
In the joint analysis of the NSABP B-31 and NCCTG N9831 studies, EBC was limited to women with operable breast cancer at high risk, defined as HER2-positive and axillary lymph node positive or HER2 positive and lymph node negative with high risk features (tumor size > 1 cm and ER negative or tumor size > 2 cm, regardless of hormonal status).
Ogivri indeholder: 
What Ogivri contains
Ogivri er, i kombination med capecitabin eller 5-fluoruracil og cisplatin, indiceret til behandling af voksne patienter med HER2-positivt metastatisk adenokarcinom i ventriklen eller den gastroøsofageale overgang, som ikke tidligere har fået anticancer-behandling for deres metastatiske sygdom. 
Ogivri in combination with capecitabine or 5-fluorouracil and cisplatin is indicated for the treatment of adult patients with HER2 positive metastatic adenocarcinoma of the stomach or gastroesophageal junction who have not received prior anti-cancer treatment for their metastatic disease.