natgillin/translations-raw huggingface dataset:
Et multi-center, randomiseret dobbelt-blindet studie sammenlignende cabozantinib (N = 219) med placebo (N = 111) blev gennemført hos patienter med inoperable, lokalt fremskreden eller metastatisk MTC og dokumenteret radiografisk sygdomsprogression inden for 14 måneder forud for indtræden i studie. 
A multi-center, randomized double-blind study comparing cabozantinib (N = 219) with placebo (N = 111) was conducted in patients with unresectable locally advanced or metastatic MTC and documented radiographic disease progression within 14 months prior to study entry.
ORR var henholdsvis 27,9 % og 0 % for forsøgspersoner i cabozantinib-armen og placebo-armen (p<0,0001; Tabel 2). 
The ORR was 27.9% and 0% for subjects in the cabozantinib arm and placebo arm, respectively (p<0.0001; Table 2).
• Svaghed eller nedsat følelse eller prikken i lemmerne 
• Weakness or reduced sensation or tingling in the limbs
I tilfælde af vedvarende hypertension på trods af anti-hypertensiver, bør dosis af cabozantinib reduceres. 
In the case of persistent hypertension despite use of anti-hypertensives, the cabozantinib dose should be reduced.
Undgå at blive gravid under behandlingen med COMETRIQ. 
Avoid becoming pregnant while being treated with COMETRIQ.
RET-mutation negative patienter uden bevis for RAS mutation (n=33) udviste en nedsat PFS-fordel på cabozantinib (HR på 0,87) og en lavere responsrate på 18 % sammenlignet med andre mutationsundergrupper. 
RET mutation negative patients with no evidence of RAS mutation (n=33) showed a decreased PFS benefit on cabozantinib (HR of 0.87) and a lower response rate of 18% compared to other mutational subgroups.
• Lysnen af huden, hud i flager, usædvanlig bleg hud 
• Lightening of skin, flakey skin, unusual pale skin
Opbevares i den originale emballage til beskyttelse mod fugt. 
Store in the original package in order to protect from moisture.
Gentagen daglig dosering af cabozantinib på 140 mg i 19 dage resulterede i circa en 4- til 5-dobbelt middel cabozantinib akkumulation (baseret på AUC) sammenlignet med administration af en enkelt dosis; steady state opnås på cirka dag 15. 
Repeat daily dosing of cabozantinib at 140 mg for 19 days resulted in an approximately a 4- to 5-fold mean cabozantinib accumulation (based on AUC) compared to a single dose administration; steady state is achieved by approximately Day 15.
• En tilstand, der kaldes posterior reversibel encefalopati syndrom (PRES) eller reversibel posterior leukoencefalopati syndrom (RPLS), der har symptomer såsom krampeanfald, 
• A condition called posterior reversible encephalopathy syndrome (PRES) or reversible posterior leukoencephalopathy syndrome (RPLS), which has symptoms such as seizures, headaches,
Cabozantinib bør anvendes med forsigtighed til patienter med en anamnese for forlængelse af QTinterval, patienter, der tager anti-arytmetika, eller patienter med præ-eksisterende hjertelidelse, bradykardi eller elektrolytforstyrrelser. 
Cabozantinib should be used with caution in patients with a history of QT interval prolongation, patients who are taking antiarrhythmics, or patients with relevant pre-existing cardiac disease, bradycardia, or electrolyte disturbances.
En oral undersøgelse børe foretages forud for start med cabozantinib og periodisk under behandlingen med cabozantinib. 
An oral examination should be performed prior to initiation of cabozantinib and periodically during cabozantinib therapy.
Tabel 1: Bivirkninger rapporteret med cabozantinib 
Table 1: Adverse reactions reported with cabozantinib
• Sår, der har svært ved at hele op 
• Wounds that have difficulties healing
• Blodpropper i arterierne 
• Blood clots in the arteries
Cabozantinib bør seponeres hos patienter, som udvikler et akut myokardieinfarkt eller nogen anden klinisk signifikant arteriel thromboembolisk komplikation. 
Cabozantinib should be discontinued in patients who develop an acute myocardial infarction or any other clinically significant arterial thromboembolic complication.
Psykiske forstyrrelser angst, depression, konfus tilstand abnorme drømme, delirium 
Psychiatric disorders anxiety, depression, confusional state abnormal dreams, delirium
Cabozantinib bør seponeres, hvis hypertension er svær og vedvarende på trods af anti-hypertensiv terapi og dosisreduktion af cabozantinib. 
Cabozantinib should be discontinued if hypertension is severe and persistent despite anti-hypertensive therapy and dose reduction of cabozantinib.
Patienterne bør derfor overvåges nøje under de første otte ugers behandling (se pkt. 
Patients should therefore be closely monitored during the first eight weeks of therapy (see section 4.4).
4,0 måneder 
4.0 months
Hjerte atrieflimmer angina pectoris, supraventrikulær takykardi myokardieinfarkt 
Cardiac disorders atrial fibrillation angina pectoris, supraventricular tachycardia myocardial infarction
20 mg og 80 mg 
20 mg and 80 mg
Cabozantinib er et lille molekyle, der hæmmer multiple receptortyrosinkinaser (RTK'er) impliceret i tumorvækst og angiogenese, patologisk knogle genmodellering og metastatisk progression af cancer. 
Cabozantinib is a small molecule that inhibits multiple receptor tyrosine kinases (RTKs) implicated in tumour growth and angiogenesis, pathologic bone remodeling, and metastatic progression of cancer.
Hvert blisterkort indeholder tilstrækkelig medicin til 7 dage. 
Each blister card contains enough medicine for 7 days.
Samtidige administreret lægemidler 
Concomitant medicinal products
Ligeledes kan visse andre lægemidler påvirke den måde, som COMETRIQ fungerer. 
Also, some medicines can affect the way COMETRIQ works.
Kliniske data i medullær thyroideacancer 
Clinical data in medullary thyroid cancer
4.5 Interaktion med andre lægemidler og andre former for interaktion Virkningen af andre lægemidler på cabozantinib 
4.5 Interaction with other medicinal products and other forms of interaction
Hos kaniner producerede cabozantinib ændringer i føtalt bløddelsvæv (reduceret størrelse på milten, lille eller manglende intermediær lunge-del) og øget føtal incidens af totale misdannelser. 
In rabbits, cabozantinib produced foetal soft tissue changes (reduced spleen size, small or missing intermediate lung lobe) and increased foetal incidence of total malformations.
Cabozantinib bør seponeres hos patienter, der oplever en GI perforation eller en GI eller ikke-GI fistel. 
Cabozantinib should be discontinued in patients who experience a GI perforation or a GI or non-GI fistula.
Kontrol af formodede lægemiddelbivirkninger kan betyde midlertidig seponering og/eller dosisreduktion ved behandlingen med COMETRIQ. 
Management of suspected adverse drug reactions may require temporary interruption and/or dose reduction of COMETRIQ therapy.
COMETRIQ indeholder 
What COMETRIQ contains
Hvis du har glemt at tage COMETRIQ 
If you forget to take COMETRIQ
Ikke almindelig (≥1/1.000 til 
Uncommon (1/1,000 to
Behandling med cabozantinib bør om muligt stoppes mindst 28 dage forud for planlagt operation. 
Cabozantinib treatment should be stopped at least 28 days prior to scheduled surgery, if possible.
I tilfælde af mistanke om overdosering bør cabozantinib seponeres og understøttende behandling skal indledes. 
In the event of suspected overdose, cabozantinib should be withheld and supportive care instituted.
Kvinder i den fertile alder/antikonception hos mænd og kvinder Kvinder i den fertile alder skal tilrådes at undgå graviditet, mens de får cabozantinib. 
Women of childbearing potential/Contraception in males and females Women of childbearing potential must be advised to avoid pregnancy while on cabozantinib.
Thromboemboliske bivirkninger 
Thromboembolic events
Cabozantinib kan derfor have potentialet til at øge plasmakoncentrationerne af co-administrerede substrater af P-gp. 
Therefore, cabozantinib may have the potential to increase plasma concentrations of co-administered substrates of P-gp.
Du bør ikke spise noget i mindst 2 timer før, du tager COMETRIQ og i 1 time efter at have taget lægemidlet. 
You should not eat anything for at least 2 hours before taking COMETRIQ and for 1 hour after taking the medicine.
I tilfælde af hypertensiv krise, bør cabozantinib seponeres. 
In case of hypertensive crisis, cabozantinib should be discontinued.
Det skal du vide, før du begynder at tage COMETRIQ 3. 
What you need to know before you take COMETRIQ 3.
I det 2-årige karcinogenicitetsstudie med rotter bestod de cabozantinib-relaterede neoplastiske fund af en øget forekomst af benignt fæokromocytom, alene eller i kombination med malignt fæokromocytom/komplekst malignt fæokromocytom i binyremarven hos begge køn ved eksponering et stykke under den tilsigtede eksponering hos mennesker. 
In the 2-year rat carcinogenicity study, cabozantinib-related neoplastic findings consisted of an increased incidence of benign pheochromocytoma, alone or in combination with malignant pheochromocytoma/complex malignant pheochromocytoma of the adrenal medulla in both sexes at exposures well below the intended exposure in humans.
Hos rotte og hund i gentaget-dosis toksicitetsstudier op til 6 måneders varighed, var målorganer for toksicitet mave-tarmkanalen, lymfevæv, nyre-, binyre- og reproduktionsvejs-væv. 
In rat and dog repeat-dose toxicity studies up to 6 months duration, target organs for toxicity were GI tract, bone marrow, lymphoid tissues, kidney, adrenal and reproductive tract tissues.
EVENTUELLE SÆRLIGE FORHOLDSREGLER VED BORTSKAFFELSE AF IKKE ANVENDT LÆGEMIDDEL SAMT AFFALD HERAF Ikke anvendt lægemiddel samt affald heraf skal bortskaffes i henhold til lokale retningslinjer. 
SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE Any unused product or waste material should be disposed of in accordance with local requirements.
Sort jernoxid (E172) (kun 20 mg kapsler) Rød jernoxid (E172) (kun 80 mg kapsler) Titandioxid (E171) 
Black iron oxide (E172) (20 mg capsules only) Red iron oxide (E172) (80 mg capsules only) Titanium dioxide (E171)
Proteinbindingen var ikke ændret hos forsøgspersoner med let til moderat nedsat nyre- eller leverfunktion. 
Protein binding was not altered in subjects with mild or moderately impaired renal or hepatic function.
Juvenile rotter (sammenlignelig med en >2 år gammel pædiatrisk population), der fik cabozantinib, udviste øgede WBC-parametre, nedsat hæmatopoiese, pubertetsalder/umodent kvindeligt reproduktionssystem (uden forsinket vaginal åbning), abnormaliteter af tænderne, reduceret mineralindhold og densitet af knoglerne, leverpigmentering og hyperplasi af galdeveje. 
Juvenile rats (comparable to a >2 year old pediatric population) administered cabozantinib showed increased WBC parameters, decreased haematopoiesis, pubescent/immature female reproductive system (without delayed vaginal opening), tooth abnormalities, reduced bone mineral content and density, liver pigmentation and bile duct hyperplasia.
• Hudsår, cyster, røde pletter i ansigtet eller på lårene 
• Skin ulcers, cysts, red spots on the face or thighs
Derfor skal samtidig anvendelse af MRP2-hæmmere (f.eks. ciclosporin, efavirenz, emtricitabin) ske med forsigtighed. 
Therefore, concomitant use of MRP2 inhibitors (e.g. cyclosporine, efavirenz, emtricitabine) should be approached with caution.
• Nedsat appetit, vægttab, ændret smagsans 
• Decreased appetite, weight loss, altered sense of taste
Cabozantinib udviste dosis-relateret hæmning af tumorvækst, tumor regression og/eller hæmmede metastase i en lang række præ-kliniske tumormodeller. 
Cabozantinib exhibited dose-related tumour growth inhibition, tumor regression, and/or inhibited metastasis in a broad range of preclinical tumour models.
cabozantinib hos raske frivillige, blev cirka 81 % af den totalt administrerede radioaktivitet genfundet med 54 % i fæces og 27 % i urin. 
Within a 48-day collection period after a single dose of 14C-cabozantinib in healthy volunteers, approximately 81% of the total administered radioactivity was recovered with 54% in faeces and 27% in urine.
11,2 måneder 
11.2 months
• Blodpropper i venerne og i lungerne 
• Blood clots in the veins and the lungs
Cabozantinib bør seponeres hos patienter, der udvikler nefrotisk syndrom. 
Cabozantinib should be discontinued in patients who develop nephrotic syndrome.
Sådan skal du tage COMETRIQ 4. 
How to take COMETRIQ 4.
• Infektion og inflammation i lungen, kollaps af lunge 
• Infection and inflammation in the lung, collapse of lung
Cabozantinib bør ikke gives til patienter med alvorlig hæmoragi eller nylig hæmoptyse. 
Cabozantinib should not be administered to patients with serious haemorrhage or recent haemoptysis.
Samtidig behandling med potente CYP3A4-hæmmere, der kan øge plasmakoncentrationerne af cabozantinib, bør anvendes med forsigtighed. 
Concomitant treatment with strong CYP3A4 inhibitors, which may increase cabozantinib plasma concentrations, should be used with caution.
Patienter bør advares mod at tage et P-gp substrat (f.eks. fexofenadin, aliskiren, ambrisentan, dabigatran etexilat, digoxin, colchicin, maraviroc, posaconazol, ranolazin, saxagliptin, sitagliptin, talinolol, tolvaptan), mens de får cabozantinib. 
Subjects should be cautioned regarding taking a P-gp substrate (e.g., fexofenadine, aliskiren, ambrisentan, dabigatran etexilate, digoxin, colchicine, maraviroc, posaconazole, ranolazine, saxagliptin, sitagliptin, talinolol, tolvaptan) while receiving cabozantinib.
Et måltid med højt fedtindhold øgede moderat Cmax - og AUC-værdier (henholdsvis 41 % og 57 %) relativt til fastende tilstande hos raske frivillige, der fik en enkelt 140 mg oral cabozantinib dosis. 
A high-fat meal moderately increased Cmax and AUC values (41% and 57%, respectively) relative to fasted conditions in healthy volunteers administered a single 140 mg oral cabozantinib dose.
Cabozantinib bør seponeres hos patienter med sårhelingskomplikationer, der kræver medicinsk intervention. 
Cabozantinib should be discontinued in patients with wound healing complications requiring medical intervention.
COMETRIQ er indiceret til behandling af voksne patienter med progressiv, inoperable, lokal fremskreden eller metastatisk thyroideacarcinom. 
COMETRIQ is indicated for the treatment of adult patients with progressive, unresectable locally advanced or metastatic medullary thyroid carcinoma.
Resultatet af PFS-analysen, baseret på den centrale gennemgang RECIST vurdering, påviste en statistisk signifikant forskel i varigheden af PFS med cabozantinib versus placebo: Median varigheden var 11,2 måneder for forsøgspersoner i cabozantinib-armen versus 4,0 måneder for forsøgspersoner i placebo-armen (stratifieret fareratio [HR] = 0,28; 95 % CI: 0,19, 0,40; p<0,0001; Figur 1). 
The result of the PFS analysis, based on the central review RECIST assessment, demonstrated a statistically significant difference in the duration of PFS with cabozantinib versus placebo: the median duration was 11.2 months for subjects in the cabozantinib arm versus 4.0 months for subjects in the placebo arm (stratified Hazard Ratio [HR] = 0.28; 95% CI: 0.19, 0.40; p<0.0001; Figure 1).
COMETRIQ bør ikke tages sammen med mad. 
COMETRIQ should not be taken with food.
Patienter med svært nedsat leverfunktion er ikke blevet undersøgt. 
Patients with severe renal impairment have not been studied.
Ved invasive dentale indgreb bør behandling med cabozantinib om muligt stoppes mindst 28 dage forud for den planlagte operation. 
For invasive dental procedures, cabozantinib treatment should be held at least 28 days prior to scheduled surgery, if possible.
• Inflammation af abdomen eller bugspytkirtlen 
• Inflammation of the abdomen or pancreas
Øre og labyrint ørepine, tinnitus hypoacusis 
Ear and labyrinth disorders ear pain, tinnitus hypoacusis
En signifikant forbedring i OS blev observeret i undergruppen af RET-M918T-mutationspositive patienter (n=81/219 i cabozantinib-armen): 44,3 måneder i cabozantinib-armen vs. 18,9 måneder i placebo-armen (HR = 0,60; p = 0,0255). 
A significant improvement in OS was observed in the subgroup of RET M918T mutation positive patients (n=81/219 cabozantinib arm): 44.3 months in the cabozantinib arm vs. 18.9 months in the placebo arm (HR = 0.60, p = 0.0255).
NOAEL for embryo-føtal toksicitet og teratogene fund var under humane kliniske eksponeringsniveauer ved den tilsigtede terapeutiske dosis. 
NOAEL for embryo-foetal toxicity and teratogenic findings were below human clinical exposure levels at intended therapeutic dose.
14,6 måneder 
14.6 months
Aktivt stof: cabozantinib (S)-malat. 
The active substance is cabozantinib (S)-malate.
Patienter med nedsat hjertefunktion 
Patients with cardiac impairment
Niveauet uden observerede bivirkninger (NOAEL) for disse fund var under humane kliniske eksponeringsniveauer ved den tilsigtede terapeutiske dosis. 
The no observed adverse effect level (NOAEL) for these findings were below human clinical exposure levels at intended therapeutic dose.
Dosisjustering er ikke nødvendig, når midler til modificering af gastrisk pH (dvs. PPI'er, H2-receptorantagonister og antacida) administreres sammen med cabozantinib. 
No dose adjustment is indicated when gastric pH modifying agents (i.e., PPIs, H2 receptor antagonists, and antacids) are co-administered with cabozantinib.
26,6 måneder 
26.6 months
Cabozantinib bør anvendes med forsigtighed hos patienter med risiko for, eller som har en anamnese, for disse bivirkninger. 
Cabozantinib should be used with caution in patients who are at risk for, or who have a history of, these events.
Patienter, som for nylig har fået strålebehandling, har inflammatorisk tarmsygdom (f.eks. Crohn's sygdom, ulcerativ colitis, peritonitis eller diverticulitis), har tumorinfiltration af trachea, bronkierne eller øsofagus, har komplikationer fra tidligere GI-kirurgi (især i forbindelse med forsinket eller ufuldstændig opheling) eller har komplikationer fra tidligere strålebehandling af thorakshulen (inklusive mediastinum), bør omhyggeligt evalueres inden indledning af behandling med cabozantinib, og de bør efterfølgende monitoreres tæt for symptomer på perforationer og fistler. 
Patients who have had recent radiotherapy, have inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, peritonitis, or diverticulitis), have tumour infiltration of trachea, bronchi, or oesophagus, have complications from prior GI surgery (particularly when associated with delayed or incomplete healing), or have complications from prior radiation therapy to the thoracic cavity (including mediastinum) should be carefully evaluated before initiating cabozantinib therapy and subsequently they should be monitored closely for symptoms of perforations and fistulas.
Der var fire metaboliter tilstede i plasma ved eksponeringer (AUC) større end 10 % af moderstoffet: XL184-N-oxid, XL184 amid spaltningsprodukt, XL184 monohydroxysulfat og 6-desmethylamid spaltningsprodukt sulfat. 
Four metabolites were present in plasma at exposures (AUC) greater than 10% of parent: XL184-N-oxide, XL184 amide cleavage product, XL184 monohydroxy sulfate, and 6-desmethyl amide cleavage product sulfate.
• Brystsmerter, som skyldes blokeringer i arterierne, hurtig hjertefrekvens 
• Chest pain due to blockage in arteries, rapid heartbeat
• Krampeanfald, hovedpiner, konfusion eller problemer med at koncentrere sig. 
• Seizures, headaches, confusion, or finding it difficult to concentrate.
Den endelige analyse af OS blev gennemført, efter at 218 hændelser (dødsfald) var forekommet og viser en tendens til en øgning i median overlevelse på 5,5 måneder i cabozantinib-armen: Median (måneder) 26,6 for cabozantinib vs. 21,1 for placebo (HR = 0,85 [95 % CI: 0,64-1,12], p = 0,2409). 
The final analysis of OS was conducted after 218 events (deaths) occurred and shows a trend for an increase in median survival of 5.5 months in the cabozantinib arm: median (months) 26.6 cabozantinib vs. 21.1 placebo (HR = 0.85 [95% CI: 0.64, 1.12], p = 0.2409).
Dette kunne være tegn på knoglebeskadigelse af kæben (osteonekrose). 
These could be signs of bone damage in the jaw (osteonecrosis).
Infektioner og parasitære sygdomme absces (inklusive visceral, hud, tand), pneumoni, folliculitis, svampeinfektion (inklusive hud, oral, genital) 
Infections and infestations abscess (including visceral, skin, tooth), pneumonia, folliculitis, fungal infection (including skin, oral, genital)
hovedpine, konfusion, eller besvær med at koncentrere sig 
confusion, or finding it difficult to concentrate
Cabozantinib bør anvendes med forsigtighed hos patienter med let eller moderat nedsat nyrefunktion. 
Cabozantinib should be used with caution in patients with mild or moderate renal impairment.
Ydermere blev der observeret hypospermatogenese hos hanhunde ved eksponeringsniveauer under det kliniske eksponeringsniveau ved den tilsigtede terapeutiske dosis til mennesker. 
Further, hypospermatogenesis was observe in male dogs at exposure levels below human clinical exposure levels at intended therapeutic dose.
Behandling med cabozantinib bør seponeres hos patienter med RPLS. 
Cabozantinib treatment should be discontinued in patients with RPLS.
Administration af protonpumpe-hæmmeren (PPI) esomeprazol (40 mg daglig i 6 dage) sammen med en enkelt dosis 100 mg cabozantinib til raske frivillige resulterede ikke i nogen klinisk signifikant effekt på cabozantinibs plasmaeksponering (AUC). 
Co-administration of proton pump inhibitor (PPI) esomeprazole (40 mg daily for 6 days) with a single dose of 100 mg cabozantinib to healthy volunteers resulted in no clinically-significant effect on plasma cabozantinib exposure (AUC).
COMETRIQ 80 mg kapsler er orange og har “XL184 80mg” trykt på den ene side. 
COMETRIQ 80 mg capsules are orange and have “XL184 80mg” printed on one side.
Brug af COMETRIQ sammen med mad 
Taking COMETRIQ with food
INFORMATION I BRAILLESKRIFT COMETRIQ 20 mg 
INFORMATION IN BRAILLE COMETRIQ 20 mg
Metabolisme og ernæring nedsat appetit, hypokalcæmi, hypofosfatæmi, hyperbilirubinæmi, hypokaliæmi, hypomagnesiæmi dehydrering, hypoalbuminæni 
Metabolism and nutrition disorders decreased appetite, hypocalcaemia, hypophosphataemia, hyperbilirubinemia, hypokalaemia, hypomagnesaemia dehydration, hypoalbuminaemia
HR: 0,85 (0,64-1,12) p = 0,2409 
21.1 months HR: 0.85 (0.64, 1.12) p = 0.2409
Cabozantinib var en hæmmer (IC50 = 7,0 μM), men ikke et substrat, af P-gp transportaktiviteter i et torettet assay-system, der anvender MDCK-MDR1 celler. 
Cabozantinib was an inhibitor (IC50 = 7.0 μM), but not a substrate, of P-gp transport activities in a bi-directional assay system using MDCK-MDR1 cells.
De mest almindelige laboratorieabnormaliteter var øget aspartat aminotransferase (ASAT), øget alanin aminotransferase (ALAT), øget alkalisk fosfatase (ALP), lymfopeni, hypokalcæmi, neutropeni, thrombocytopeni, hypofosfatæmi, hyperbililirubinæmi, hypomagnesiæmi og hypokaliæmi. 
The most common laboratory abnormalities were increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), increased alkaline phosphatase (ALP), lymphopenia, hypocalcaemia, neutropenia, thrombocytopenia, hypophosphataemia, hyperbilirubinemia, hypomagnesaemia, and hypokalaemia.
PFSresultaterne var konsistente på tværs af alle evaluerede baseline og demografiske undergrupper, inklusive forudgående behandling med tyrosinkinase-hæmmere (der kan have bestået af midler målrettet mod veje forbundet med anti-angiogenese), RET-mutationsstatus (inklusive forsøgspersoner dokumenteret ikke at have RET-mutationer), forudgående anticancer- eller strålebehandlingsstatus eller eksistensen af knogle-metastaser. 
The PFS results were consistent across all baseline and demographic subgroups evaluated, including prior therapy with tyrosine kinase inhibitors (which may have consisted of agents targeting pathways associated with anti-angiogenesis), RET mutational status (including subjects documented not to have RET mutations), prior anticancer or radiotherapy status, or the existence of bone metastases.