Study Design and Patient Characteristics
Studied in the first-line setting across MSKCC risk groups
aNorth America and Western Europe vs “Rest of the World.”
bRandomization was stratified according to Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk groups: favorable vs intermediate vs poor.
cClinical data are presented from the KEYTRUDA + LENVIMA and sunitinib arms.
dAdministration of KEYTRUDA with LENVIMA was permitted beyond RECIST-defined disease progression, if the patient was clinically stable and considered by the investigator to be deriving clinical benefit.
|Median age||62 years (range: 29 to 88 years; 42% aged 65 or older)|
|18% 70 to 80||82% 90 to 100|
|Lung (68%)||Lymph node (45%)||Bone (25%)|
1L = first line; IRC = independent radiologic review committee; ORR = objective response rate; OS = overall survival; PD-L1 = programmed death ligand 1; PFS = progression-free survival; RECIST v1.1 = Response Evaluation Criteria In Solid Tumors v1.1.
Superior PFS vs sunitinib (HRe=0.39; 95% CI, 0.32–0.49; Pf<0.0001)
eHazard ratio is based on a Cox Proportional Hazards Model. Stratified by geographic region and MSKCC prognostic groups.
fTwo-sided P value based on stratified log-rank test.
gTumor assessments were based on RECIST v1.1; data cutoff date = 28 Aug 2020.
HR = hazard ratio; CI = confidence interval.
Superior OS vs sunitinib (HRe=0.66; 95% CI, 0.49–0.88; Pf=0.0049)
|KEYTRUDA + LENVIMA (n=355)||Sunitinib (n=357)|
|Number of deaths, n (%)||80 (23%)||101 (28%)|
|Median OS in months||NR (95% CI, 33.6–NR)||NR (95% CI, NR–NR)|
|Hazard ratioe||0.66 (95% CI, 0.49–0.88)|
hData cutoff date = 28 Aug 2020.
NR = not reached.
hData cutoff date = 28 Aug 2020
Additional endpoint: Objective response rates
Superior ORR vs sunitinib: 71% (n=252) with KEYTRUDA + LENVIMA vs 36% (n=129) with sunitinib (Pi<0.0001)
iTwo-sided P value based upon CMH test.
jTumor assessments were based on RECIST v1.1; only confirmed responses are included for ORR. Data cutoff date = 28 Aug 2020.
CR = complete response; PR = partial response; CMH = Cochran-Mantel-Haenszel.
Adverse reactions in the KEYNOTE-581/CLEAR trial
The median duration of exposure to KEYTRUDA + LENVIMA was 17 months (range: 0.1 to 39).
Increased blood creatinine
Multiple organ dysfunction syndrome
Hemorrhagic events (5%)
Myocardial infarction (3%)
Acute kidney injury (2%)
Adrenal insufficiency (2%)
Most common (≥3) adverse reactions in patients receiving KEYTRUDA + LENVIMA (n=352) that resulted in interruption of KEYTRUDA
|Adverse Reactions||% of Patients|
|Acute kidney injury||3|
Most common (≥5%) adverse reactions in patients receiving KEYTRUDA + LENVIMA (n=352) that resulted in dose reduction or interruption of LENVIMA
|Adverse Reactions||% of Patients|
ALT = alanine aminotransferase.
kIncludes asthenia, fatigue, lethargy, and malaise.
lIncludes diarrhea and gastroenteritis.
mIncludes arthralgia, arthritis, back pain, bone pain, breast pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, musculoskeletal stiffness, myalgia, neck pain, non-cardiac chest pain, pain in extremity, and pain in jaw.
nIncludes hypothyroidism, increased blood thyroid stimulating hormone, and secondary hypothyroidism.
oIncludes essential hypertension, increased blood pressure, increased diastolic blood pressure, hypertension, hypertensive crisis, hypertensive retinopathy, and labile blood pressure.
pIncludes aphthous ulcer, gingival pain, glossitis, glossodynia, mouth ulceration, mucosal inflammation, oral discomfort, oral mucosal blistering, oral pain, oropharyngeal pain, pharyngeal inflammation, and stomatitis.
qIncludes decreased appetite and early satiety.
rIncludes genital rash, infusion site rash, penile rash, perineal rash, rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, and rash pustular.
sIncludes hemoglobinuria, nephrotic syndrome, and proteinuria.
tIncludes palmar erythema, palmar-plantar erythrodysesthesia syndrome, and plantar erythema.
uIncludes all hemorrhage terms. Hemorrhage terms that occurred in 1 or more subjects in either treatment group include anal hemorrhage, aneurysm ruptured, blood blister, blood loss anemia, blood urine present, catheter site hematoma, cerebral microhemorrhage, conjunctival hemorrhage, contusion, diarrhea hemorrhagic, disseminated intravascular coagulation, ecchymosis, epistaxis, eye hemorrhage, gastric hemorrhage, gastritis hemorrhagic, gingival bleeding, hemorrhage urinary tract, hemothorax, hematemesis, hematoma, hematochezia, hematuria, hemoptysis, hemorrhoidal hemorrhage, increased tendency to bruise, injection site hematoma, injection site hemorrhage, intra-abdominal hemorrhage, lower gastrointestinal hemorrhage, Mallory-Weiss syndrome, melaena, petechiae, rectal hemorrhage, renal hemorrhage, retroperitoneal hemorrhage, small intestinal hemorrhage, splinter hemorrhages, subcutaneous hematoma, subdural hematoma, subarachnoid hemorrhage, thrombotic thrombocytopenic purpura, tumor hemorrhage, traumatic hematoma, and upper gastrointestinal hemorrhage.
vIncludes abdominal discomfort, abdominal pain, abdominal rigidity, abdominal tenderness, epigastric discomfort, lower abdominal pain, and upper abdominal pain.
wIncludes alanine aminotransferase increased, aspartate aminotransferase increased, blood bilirubin increased, drug-induced liver injury, hepatic enzyme increased, hepatic failure, hepatic function abnormal, hepatocellular injury, hepatotoxicity, hyperbilirubinemia, hypertransaminasemia, immune-mediated hepatitis, liver function test increased, liver injury, transaminases increased, and gamma-glutamyltransferase increased.
xIncludes acute kidney injury, azotemia, blood creatinine increased, creatinine renal clearance decreased, hypercreatininemia, renal failure, renal impairment, oliguria, glomerular filtration rate decreased, and nephropathy toxic.
AST = aspartate aminotransferase.
KEYTRUDA, in combination with LENVIMA, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma.
NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.
Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.2
Selected Safety Information for
MSI-H = microsatellite instability-high; pMMR = mismatch repair proficient; ALT = alanine aminotransferase.
Selected Safety Information for
Perform an oral examination prior to treatment with LENVIMA and periodically during LENVIMA treatment. Advise patients regarding good oral hygiene practices and to consider having preventive dentistry performed prior to treatment with LENVIMA and throughout treatment with LENVIMA.
Avoid invasive dental procedures, if possible, while on LENVIMA treatment, particularly in patients at higher risk. Withhold LENVIMA for at least 1 week prior to scheduled dental surgery or invasive dental procedures, if possible. For patients requiring invasive dental procedures, discontinuation of bisphosphonate treatment may reduce the risk of ONJ.
Withhold LENVIMA if ONJ develops and restart based on clinical judgement of adequate resolution.
CNS = central nervous system; MRI = magnetic resonance imaging; QTc = corrected QT interval; ALT = alanine aminotransferase.
Before prescribing LENVIMA® (lenvatinib), please read the accompanying Prescribing Information and Patient Information.