FrancophonIA/ELRC3.0 huggingface dataset:
English: In the case of vomiting a replacement dose should not be taken; the next dose should be taken at the next scheduled time.
Croatian: U slučaju povraćanja zamjensku dozu ne treba uzimati; sljedeću dozu treba uzeti u sljedeće planirano vrijeme.
English: The safety and efficacy of tivozanib in children and adolescents aged below 18 years have not been established.
Croatian: Sigurnost i djelotvornost tivozaniba u djece i adolescenata u dobi do 18 godina nisu ustanovljene.
English: Risk factors for proteinuria include high blood pressure.
Croatian: Faktori rizika za proteinuriju uključuju visoki krvni tlak.
English: These are all symptoms of high blood pressure.
Croatian: Sve su to simptomi povišenog krvnog tlaka.
English: In vitro protein binding studies have shown that tivozanib is > 99% bound to plasma proteins.
Croatian: In vitro ispitivanja vezivanja proteina pokazuju da je > 99% tivozaniba vezano na proteine u plazmi.
English: Palmar-plantar erythrodysaesthesia syndrome / Hand foot skin reaction (PPE/HFS)
Croatian: Palmoplantarna eritrodizestezija / Sindrom reakcije kože šaka i stopala (PPE/HFS)
English: In the pivotal study, the dose was reduced for grade 3 events and interrupted for grade 4 events.
Croatian: U pivotalnom ispitivanju doza je smanjena za događaje 3. stupnja i privremeno prekinuta za događaje 4 stupnja.
English: Healthcare professions should be aware that elderly patients may be at increased risk of adverse reactions.
Croatian: Zdravstveni radnici moraju biti svjesni činjenice da kod starijih bolesnika može postojati povećan rizik od nuspojava.
English: Hypothyroidism should be treated according to standard medical practice.
Croatian: Hipotireoza se treba liječiti u skladu s uobičajenom medicinskom praksom.
English: Blocking the action of VEGF prevents the formation of new blood vessels.
Croatian: Blokiranjem aktivnosti VEGF-a sprječava se stvaranje novih krvnih žila.
English: Fotivda can increase your blood pressure.
Croatian: Fotivda može povisiti Vaš krvni tlak.
English: The other ingredients are: - Capsule content: mannitol, magnesium stearate.
Croatian: Drugi sastojci su: - Sadržaj kapsule: manitol, magnezijev stearat.
English: Treatment decision, especially in patients who are at risk for VTEs, should be based on individual patient benefit/risk assessment.
Croatian: Odluku o terapiji, naročito kod bolesnika kod kojih postoji rizik od VTE, trebalo bi temeljiti na procjeni koristi/rizika pojedinog bolesnika.
English: • if you have high blood pressure.
Croatian: • ako imate povišen krvni tlak.
English: Do not use this medicine after the expiry date which is stated on the carton and bottle after EXP.
Croatian: Ovaj lijek se ne smije upotrijebiti nakon isteka roka valjanosti navedenog na kutiji i bočici iza oznake EXP.
English: There is no specific treatment or antidote for tivozanib overdose.
Croatian: Ne postoji posebna terapija niti antidot za slučaj predoziranja tivozanibom.
English: common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000) and not known (cannot be estimated from available data).
Croatian: Učestalost nuspojava definirana je kao: vrlo često (≥ 1/10), često (≥ 1/100 i < 1/10), manje često (≥ 1/1000 i < 1/100), rijetko (≥ 1/10 000 i < 1/1000) i nepoznato (ne može se procijeniti iz dostupnih podataka).
English: Tell your doctor straightaway if you have taken more than your prescribed dose of 1 capsule per day.
Croatian: Odmah obavijestite liječnika da ste uzeli više od propisane doze od 1 kapsule dnevno.
English: In a controlled clinical study (AV-951-09-301), in which 25% of patients receiving tivozanib were ≥ 65 years of age, no overall differences was observed in efficacy between elderly and younger patients (see section 4.2).
Croatian: U kontroliranom kliničkom ispitivanju (AV-951-09-301), u kojem je 25% bolesnika koji su primali tivozanib bilo staro 65 i više godina, nisu bile primijećene općenite razlike u djelotvornosti između starijih i mlađih bolesnika (vidjeti dio 4.2).
English: • rosuvastatin (a medicine used to help lower cholesterol levels in your blood);
Croatian: • rosuvastatin (lijek koji pomaže u snižavanju razina kolesterola u krvi);
English: After a single dose oral dose of [14C] tivozanib, approximately 79% of the radioactivity was recovered in the faeces and approximately 12% was found in the urine as metabolites.
Croatian: Nakon jedne peroralne doze [14C] tivozaniba, oko 79% radioaktivnosti pronađeno je u stolici i oko 12% u urinu kao metaboliti.
English: • Abnormal electrocardiogram (ECG), rapid and/or irregular heart beat.
Croatian: • Odstupanja u nalazu elektrokardiograma (EKG), brzi i/ili nepravilni otkucaji srca
English: • Increased amount of protein in the urine.
Croatian: • Povišene vrijednosti proteina u urinu
English: • Inflammation of the pancreas causing severe stomach pain which may spread to your back.
Croatian: • Upala gušterače koja izaziva snažnu bol u trbuhu koja se može širiti na leđa
English: Based on the population pharmacokinetic analysis, there is no clinically relevant effect of age, gender or race on the pharmacokinetics of tivozanib.
Croatian: Na temelju populacijske farmakokinetičke analize ne postoji klinički značajan utjecaj dobi, spola ili rase na farmakokinetička svojstva tivozaniba.
English: VEGF is a potent mitogenic factor that plays a central role in angiogenesis and vascular permeability of tumour tissues.
Croatian: VEGF je potentan mitogeni faktor koji ima središnju ulogu u angiogenezi i vaskularnoj propusnosti tumorskih tkiva.
English: Female partners of male patients taking tivozanib should also avoid pregnancy.
Croatian: Partnerice muškaraca koji uzimaju tivozanib trebale bi također izbjegavati trudnoću.
English: AST, ALT, bilirubin, and AP should be monitored before initiation of and periodically throughout treatment with tivozanib because of the potential risk of hepatotoxicity (see section 4.2).
Croatian: AST, ALT, bilirubin i AP potrebno je pratiti prije početka i redovito tijekom liječenja tivozanibom, jer postoji potencijalni rizik od hepatotoksičnosti (vidjeti dio 4.2).
English: • Memory loss.
Croatian: • Gubitak pamćenja
English: Avoid driving or using machines if you feel weak, tired, or dizzy.
Croatian: Izbjegavajte upravljanje vozilima i strojevima ako osjećate slabost, umor ili omaglicu.
English: The next most potently inhibited kinase is c-kit which is 8-fold less sensitive to inhibition by tivozanib compared to VEGFR 1, 2 and 3.
Croatian: Sljedeća kinaza koja se može najviše inhibirati je c-kit, koja je 8 puta manje osjetljiva na inhibiciju tivozanibom u usporedbi s VEGFR-om 1, 2 i 3.
English: Carcinogenesis Carcinogenicity studies have not been performed with tivozanib.
Croatian: Karcinogeneza Nisu provedena ispitivanja karcinogeneze s tivozanibom.
English: The intent-to-treat (ITT) population included 517 patients, 260 randomised to tivozanib and 257 randomised to sorafenib.
Croatian: Populacija planirana za liječenje (engl. intent-to-treat, ITT) obuhvaćala je 517 bolesnika, 260 randomiziranih na tivozanib, a 257 na sorafenib.
English: Risk factors for hypothyroidism include prior history of hypothyroidism and use of anti-thyroid medications.
Croatian: Faktori rizika za hipotireozu uključuju prethodnu povijest hipotireoze i uzimanje antitireoidnih lijekova.
English: Capsule content Mannitol
Croatian: Sadržaj kapsule Manitol
English: In vitro metabolism studies have shown that CYP3A4 and CYP1A1 are capable of metabolising tivozanib.
Croatian: In vitro ispitivanja metabolizma pokazuju da su CYP3A4 i CYP1A1 sposobni metabolizirati tivozanib.
English: Effective methods of contraception should be used by male and female patients and their partners during therapy, and for at least one month after completing therapy.
Croatian: Muški i ženski bolesnici i njihovi partneri i partnerice trebaju koristiti učinkovite metode kontracepcije tijekom trajanja terapije i najmanje mjesec dana nakon završetka terapije.
English: Tivozanib reduces the supply of blood to the cancer, which slows down the growth and spread of cancer cells.
Croatian: Tivozanib smanjuje opskrbu raka krvlju, što usporava rast i širenje stanica raka.
English: If you vomit after taking Fotivda, do not take a replacement capsule.
Croatian: Ako ste nakon uzimanja kapsule povraćali, nemojte uzimati zamjensku kapsulu.
English: Urticaria Dermatitis26
Croatian: Dermatitis26
English: Do not chew, dissolve or open the capsule before swallowing.
Croatian: Kapsulu prije gutanja nemojte žvakati, otapati ili otvarati.
English: Taking too much Fotivda makes side effects more likely or to become more severe, especially high blood pressure.
Croatian: Uzimanjem previše Fotivde vjerojatnost za pojavu nuspojava je veća i one će biti teže, naročito povišeni krvni tlak.
English: • Do not breast-feed during treatment with Fotivda, as it is not known whether the active ingredient in Fotivda passes into breast-milk.
Croatian: • Nemojte dojiti tijekom terapije Fotivdom, jer nije poznato ulazi li aktivni sastojak Fotivde u majčino mlijeko.
English: In studies that evaluated the terminal elimination phase, tivozanib had a mean t½ of 4.5 - 5.1 days.
Croatian: U ispitivanjima kojima se ocjenjivala terminalna faza eliminacije, srednja vrijednost t½ tivozaniba bila je 4,5 - 5,1 dana.
English: The maximum change in QTcF from baseline was 9.3 ms (90% CI: 5, 13.6), which occurred 2.5 hours after dosing on Day 21.
Croatian: Maksimalna promjena QTcF-a u usporedbi s početnom vrijednošću bila je 9,3 ms (90% CI: 5; 13,6), koja je nastupila 2,5 sati nakon doziranja 21. dana.
English: Talk to your doctor, pharmacist or nurse before taking Fotivda:
Croatian: Obratite se svom liječniku, ljekarniku ili medicinskoj sestri prije nego uzmete Fotivdu:
English: If you or your partner are taking hormonal contraceptives (the pill, an implant or patch) you must use an additional barrier method throughout treatment and for another month after completing treatment.
Croatian: Ako Vi ili Vaš partner(ica) koristite hormonsku kontracepciju (tablete, uložak ili flaster), morate koristiti i dodatnu mehaničku metodu kontracepcije tijekom trajanja terapije i još mjesec dana nakon završetka terapije.
English: Fotivda can have side effects that may affect your ability to drive or use machines.
Croatian: Fotivda može izazvati nuspojave koje mogu utjecati na Vašu sposobnost upravljanja vozilima ili strojevima.
English: Keep the bottle tightly closed in order to protect from moisture.
Croatian: Bočicu čuvajte čvrsto zatvorenu kako biste je zaštitili od vlage.
English: Oral use.
Croatian: Za peroralnu uporabu.
English: Tivozanib should not be used during pregnancy.
Croatian: Tivozanib se ne smije uzimati tijekom trudnoće.
English: • if you have had problems with bleeding
Croatian: • ako ste imali problema s krvarenjem
English: The primary endpoint of the study was progression-free survival (PFS) by blinded independent radiology review; key secondary endpoints included overall survival (OS) and objective response rate (ORR) by independent radiology review.
Croatian: Primarna mjera ishoda ispitivanja bilo je preživljenje bez progresije (engl. progression-free survival, PFS), na temelju neovisne slijepe radiološke procjene; ključne sekundarne mjere ishoda obuhvatile su ukupno preživljenje (engl. overall survival, OS) i stopu objektivnog odgovora (engl. objective response rate, ORR) na temelju neovisne radiološke procjene.
English: Average Cmax and AUC0-24hr were not significantly affected (8% increase and 6% decrease respectively).
Croatian: Prosječne vrijednosti Cmax i AUC0-24hr nisu se značajnije mijenjale (povećanje Cmax od 8% i smanjenje AUC0-24hr od 6%).
English: White HDPE bottle with a child resistant closure containing 21 hard capsules.
Croatian: Bijela HDPE bočica sa sigurnosnim zatvaračem za djecu u kojoj se nalazi 21 tvrda kapsula.
English: If any bleeding requires medical intervention, tivozanib should be temporarily interrupted.
Croatian: Ako krvarenje zahtijeva medicinsku intervenciju, terapiju tivozanibom potrebno je privremeno prekinuti.
English: • dexamethasone (a corticosteroid to reduce inflammation and treat disorders of the immune system);
Croatian: • deksametazon (kortikosteroid za ublažavanje upale i liječenje poremećaja imunološkog sustava);
English: • If you have or are treated for an abnormal rate and rhythm of the heartbeat (arrhythmia).
Croatian: • ako imate ili se liječite zbog abnormalne brzine i ritma otkucaja srca (aritmije).
English: In vitro studies conducted in human liver microsomes and hepatocytes evaluating the activity of CYP1A2, CYP2B6, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 suggested that tivozanib is a weak inhibitor of CYP2B6 and CYP2C8.
Croatian: In vitro ispitivanja provedena na mikrosomima i hepatocitima ljudske jetre kojima se ocjenjuje aktivnost enzima CYP1A2, CYP2B6, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 i CYP3A4 sugeriraju da je tivozanib slabi inhibitor enzima CYP2B6 i CYP2C8.
English: One patient died as a result of uncontrolled hypertension in the setting of a suspected overdose.
Croatian: Jedan bolesnik je umro od nekontrolirane hipertenzije u okolnostima u kojima je postojala sumnja na predoziranje.
English: Your doctor will monitor the effect of Fotivda on your heart by recording the electrical activity of your heart (an electrocardiogram) or by measuring your blood calcium, magnesium and potassium levels during your treatment.
Croatian: Vaš će liječnik pratiti djelovanje Fotivde na Vaše srce tijekom terapije bilježenjem električne aktivnosti srca (pomoću elektrokardiograma) ili mjerenjem vrijednosti kalcija, magnezija i kalija u krvi.
English: If tivozanib is used during pregnancy, or if the patient becomes pregnant while receiving tivozanib, the potential hazard to the foetus must be explained to the patient.
Croatian: Ako se tivozanib uzima tijekom trudnoće ili ako bolesnica zatrudni tijekom uzimanja tivozaniba, potrebno joj je objasniti potencijalne opasnosti koje postoje za fetus.
English: Treatment with Fotivda may need to be temporarily stopped.
Croatian: Terapiju Fotivdom će možda trebati privremeno prekinuti.
English: If you stop taking Fotivda
Croatian: Ako prestanete uzimati Fotivdu
English: Tivozanib must be used with caution in patients who are at risk for, or who have a history of these events (such as myocardial infarction, stroke).
Croatian: Tivozanib se mora primjenjivati pažljivo kod bolesnika kod kojih postoji rizik od ili koji imaju povijest navedenih događaja (npr. infarkt miokarda, moždani udar).
English: Pharmacotherapeutic group: antineoplastic agents, protein-kinase inhibitors, ATC code: L01XE34
Croatian: Farmakoterapijska skupina: antineoplastici, inhibitori protein kinaze, ATK oznaka: L01XE34
English: Table 1: Tabulated list of adverse reactions (presented using frequencies for all-causality adverse events)
Croatian: Tablica 1: Tablični prikaz nuspojava (prikazano koristeći učestalosti za nuspojave svih uzroka)
English: The most common adverse reactions of any grade include hypertension (47.6%), dysphonia (26.9%), fatigue (25.8%) and diarrhoea (25.5%).
Croatian: Najčešće nuspojave bilo kojeg stupnja uključuju hipertenziju (47,6%), disfoniju (26,9%), umor (25,8%) i dijareju (25,5%).
English: Magnesium stearate
Croatian: Magnezijev stearat
English: Baseline and periodic monitoring of electrocardiograms and maintenance of electrolytes (e.g. calcium, magnesium, potassium) within the normal range is recommended.
Croatian: Preporučuje se početno i redovito praćenje EKG-a i održavanje elektrolita (npr. kalcija, magnezija, kalija) unutar normalnog raspona.
English: Treatment with Fotivda may raise the risk of developing a blood clot (thrombus) in your blood vessels that could break loose and be carried by the blood stream to block another blood vessel.
Croatian: Terapija Fotivdom može povećati rizik od nastajanja krvnih ugrušaka (tromba) u Vašim krvnim žilama koji se mogu osloboditi i nošeni krvotokom začepiti drugu krvnu žilu.
English: Contraceptives
Croatian: Kontracepcijska sredstva
English: • phenobarbital, phenytoin, carbamazepine (used to treat epilepsy);
Croatian: • fenobarbital, fenitoin, karbamazepin (koriste se za liječenje epilepsije);
English: Caution is advised in patients with severe renal impairment due to limited experience and in patients undergoing dialysis as there is no experience of tivozanib in this patient population.
Croatian: Oprez se savjetuje kod bolesnika s teškim oštećenjem bubrega zbog ograničenog iskustva, kao i kod bolesnika koji su na dijalizi, zbog nepostojanja iskustva s tivozanibom kod ove populacije bolesnika.
English: Each hard capsule contains trace amounts of tartrazine (E102) (8-12% of the yellow printing ink composition) (see section 4.4).
Croatian: Jedna tvrda kapsula sadrži tartrazin (E102) u tragovima (8-12% sastava žute tinte za označavanje) (vidjeti dio 4.4).
English: Tivozanib potently and selectively blocks all 3 Vascular Endothelial Growth Factor receptors (VEGFR) and has been shown to block various VEGF-induced biochemical and biologic responses in vitro, including VEGF-ligand-induced phosphorylation of all three VEGFR 1, 2 and 3, and proliferation of human endothelial cells.
Croatian: Tivozanib potentno i selektivno blokira sva tri receptora za vaskularni endotelni faktor rasta (VEGFR) i pokazalo se da blokira i različite biokemijske i biološke odgovore inducirane VEGF-om in vitro, uključujući fosforilaciju induciranu VEGF ligandom kod svih triju VEGFR-ova 1, 2 i 3 i proliferaciju humanih endotelnih stanica.
English: Transporter in vitro studies
Croatian: In vitro ispitivanja transportera
English: It works by blocking the action of a protein called vascular endothelial growth factor (VEGF).
Croatian: Djeluje blokiranjem aktivnosti proteina poznatog pod nazivom vaskularni endotelni čimbenik rasta (engl. vascular endothelial growth factor, VEGF).
English: 3 Dysgeusia including ageusia, dysgeusia and hypogeusia 4 Memory impairment including amnesia and memory impairment 5 PRES was not observed in patients treated with tivozanib in the five RCC monotherapy studies.
Croatian: 3 Disgeuzija uključujući ageuziju, disgeuziju i hipogeuziju 4 Poremećaj pamćenja uključujući amneziju i poremećaj pamćenja 5 PRES nije zabilježen u bolesnika koji su se liječili tivozanibom u pet monoterapijskih ispitivanja RCC-a.
English: It is unknown whether tivozanib is excreted in human milk, but the potential exists.
Croatian: Nije poznato izlučuje li se tivozanib u majčino mlijeko, no za to postoji mogućnost.
English: Reproduction, mutagenesis, impairment of fertility Tivozanib may impair human fertility.
Croatian: Reproduktivnost, mutageneza, poremećaj plodnosti Tivozanib može poremetiti plodnost kod ljudi.
English: Persistent severe hypertension12
Croatian: Perzistentna teška hipertenzija12
English: Discontinuation of treatment should be considered in cases of persistent severe hypertension, posterior reversible encephalopathy syndrome (see below), or other complications of hypertension.
Croatian: Prestanak terapije trebalo bi razmotriti u slučaju perzistirajuće teške hipertenzije, sindroma posteriorne reverzibilne encefalopatije (vidi nastavak) ili nekih drugih komplikacija hipertenzije.
English: Fotivda is used to treat adults with advanced kidney cancer.
Croatian: Fotivda se koristi za liječenje odraslih bolesnika s uznapredovalim rakom bubrega.
English: • Very high blood pressure leading to a stroke; flushed skin.
Croatian: • Vrlo visok krvni tlak koji može uzrokovati moždani udar; crvenilo kože
English: Adverse reactions not observed in clinical studies, but seen in animals at exposure levels similar to clinical exposure levels and with possible relevance to clinical use were as follows.
Croatian: Nuspojave koje nisu zabilježene u kliničkim ispitivanjima, ali su zapažene u životinja pri razinama izloženosti sličnima kliničkim razinama izloženosti u ljudi i s mogućom važnošću za kliničku primjenu, bile su sljedeće.
English: All patients should have liver function tests evaluated, including aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and alkaline phosphatase (AP), to determine hepatic function before starting and during treatment with tivozanib.
Croatian: Svi bolesnici trebali bi obaviti preglede funkcije jetre, uključujući alanin aminotransferazu (ALT), aspartat aminotransferazu (AST), bilirubin i alkalnu fosfatazu (AP), kako bi se funkcija jetre utvrdila prije početka i tijekom liječenja tivozanibom.
English: Dysphonia, diarrhoea, fatigue, weight decreased, appetite decreased and hypothyroidism occurred more commonly in patients ≥ 65 years of age.
Croatian: Disfonija, dijareja, umor, gubitak težine, smanjen apetit i hipotireoza češće se javljaju kod bolesnika starijih od 65 godina.
English: Based on these data, tivozanib can be dosed with or without food (see section 4.2).
Croatian: Na temelju ovih podataka, tivozanib se može uzimati s hranom ili bez nje (vidjeti dio 4.2).
English: Before initiating Fotivda, this risk should be carefully considered in patients with risk factors such as hypertension or history of aneurysm.
Croatian: Prije početka primjene lijeka Fotivda potrebno je pažljivo razmotriti ovaj rizik u bolesnika s čimbenicima rizika kao što su hipertenzija ili aneurizma u anamnezi.
English: Treatment with Fotivda may increase the risk of bleeding.
Croatian: Terapija Fotivdom može povećati rizik od krvarenja.
English: If PRES is diagnosed, your doctor will stop treatment with Fotivda.
Croatian: Ako se dijagnosticira PRES, Vaš će liječnik prekinuti terapiju Fotivdom.
English: • if you have problems with your liver.
Croatian: • ako imate problema s jetrom.
English: When dose reduction is necessary, the tivozanib dose can be reduced to 890 microgram once daily with the normal treatment schedule of 21 days of dosing, followed by a 7-day rest period.
Croatian: Kad je potrebno smanjenje doziranja, doza tivozaniba može se smanjiti na 890 mikrograma jednom dnevno, uz uobičajeni raspored liječenja od 21 dan, nakon čega slijedi stanka od 7 dana.
English: • St. John's Wort (also known as Hypericum perforatum, a herbal remedy used for treatment of depression and anxiety) as this herbal remedy should not be used at the same time as Fotivda.
Croatian: • gospinu travu (poznatu i kao Hypericum perforatum, biljni lijek koji se koristi za liječenje depresije i tjeskobe) jer se ovaj biljni lijek ne bi smio uzimati istodobno kad i Fotivda.
English: Swelling in the lungs caused by fluid build-up.
Croatian: Oticanje unutar pluća uzrokovano nakupljanjem tekućine
English: • Coughing up blood; vomiting up blood.
Croatian: • Iskašljavanje krvi; povraćanje krvi
English: Your doctor will check you regularly, and you will normally continue to take Fotivda as long as it is working, and you do not suffer unacceptable side effects.
Croatian: Vaš će Vas liječnik redovito kontrolirati i Fotivdu ćete nastaviti normalno uzimati tako dugo dok djeluje i dok ne primijetite neprihvatljive nuspojave.
English: Fotivda may be taken with or without food (see section 5.2).
Croatian: Lijek Fotivda može se uzimati s hranom ili bez nje (vidjeti dio 5.2).
English: Fotivda should be supervised by a physician experienced in the use of anticancer therapies.
Croatian: Primjenu Fotivde treba nadzirati liječnik koji posjeduje iskustvo u primjeni terapija za liječenje raka.
English: The study included patients who had all undergone prior nephrectomy, and who had received either no prior therapy or no more than one prior systemic therapy in the metastatic setting (immunotherapy/chemotherapy); prior treatment with VEGF or mechanistic Target of Rapamycin (mTOR) targeted therapy was not allowed.
Croatian: Ispitivanje je uključivalo bolesnike koji su svi prethodno obavili nefrektomiju i koji ili do tada nisu primali nikakvu terapiju ili nisu prethodno primili više od jedne sustavne terapije za metastaze (imunoterapiju/kemoterapiju); prethodna terapija s VEGF-om ili ciljana mTOR terapija nisu bile dozvoljene.