KEYTRUDA® in combination with LENVIMA® is indicated for:

  • the treatment of adult patients with advanced (not amenable to curative surgery or radiation) or metastatic RCC with no prior systemic therapy for metastatic RCC.

Kidney Cancer Research Network of Canada (KCRNC) 2021 consensus statement3

In untreated patients with advanced clear cell renal cell carcinoma with favourable, intermediate, or poor risk (IMDC), pembrolizumab + lenvatimib is recommended as a preferred treatment option

See the complete KCRNC Guideline recommendation.

The National Comprehensive Cancer Network (NCCN) clinical practice guidelines for kidney cancer (NCCN Guidelines®)5

In patients with Stage IV clear-cell RCC, pembrolizumab + lenvatinib is recommended as a first-line preferred option across all favourable-, intermediate-, and poor-risk groups.

Please see the guidelines for complete recommendations.

Clinical Study

KEYNOTE-581/CLEAR trial: clinical study in patients with advanced or metastatic RCC.

KEYNOTE-581/CLEAR trial

KEYTRUDA® + LENVIMA® recommended dosing:

For adult patients with advanced or metastatic RCC with no prior systemic therapy for metastatic RCC1,2

Optimal medical management (i.e. treatment or therapy) for nausea, vomiting, and diarrhea should be initiated prior to any LENVIMA® therapy interruption or dose reduction; gastrointestinal toxicity should be actively treated in order to reduce the risk of development of renal impairment or failure.2

Electrolytes, liver enzymes, urinary protein, thyroid function and hypertension should be tested prior to LENVIMA® treatment and monitored periodically during LENVIMA® therapy.2

Caregivers should not open the LENVIMA® capsule, in order to avoid repeated exposure to the contents of the capsule.2

Dosing modifications

When administering LENVIMA® in combination with KEYTRUDA®, interrupt one or both drugs, dose reduce or discontinue LENVIMA® as appropriate. Withhold or discontinue KEYTRUDA® in accordance with the instructions in the KEYTRUDA® Product Monograph. No dose reductions are recommended for KEYTRUDA®.1,2

Please see the Product Monograph for complete dosing and administration recommendations.

KEYTRUDA®+ LENVIMA® adverse event (AE) management tools

For guidance on AE management in patients taking KEYTRUDA®+ LENVIMA®, download this handbook.

Download handbook

Help your patients taking KEYTRUDA®+ LENVIMA® keep track of their side effects by providing this personal diary.

Download diary

Consider KEYTRUDA® + LENVIMA® for your patients with advanced or metastatic RCC

Learn more by reviewing our patient profiles

cHL=classical Hodgkin lymphoma; PMBCL=Primary mediastinal B cell lymphoma; AE=adverse event; IMDC=International Metastatic RCC Database Consortium.

* Alternatively, the LENVIMA® capsules may be added without breaking or crushing them to a tablespoon of water or apple juice in a small glass to produce a suspension. The capsules must be left in the liquid for at least 10 minutes and stirred for at least 3 minutes to dissolve the capsule shells. The suspension is to be swallowed. After drinking, the same amount of water or apple juice (one tablespoon) must be added to the glass and swirled a few times. The additional liquid must be swallowed.2

 

References:

  1. Merck Canada Inc. KEYTRUDA® Product Monograph. March 21, 2024.
  2. Eisai Limited. LENVIMA® Product Monograph. July 19, 2023.
  3. Canil C et al. Management of advanced kidney cancer: Kidney Cancer Research Network of Canada (KCRNC) consensus update 2021. Can Urol Assoc J. 2021;15(4):84‒97.
  4. Medical Council of Canada. Clinical laboratory tests: Adult normal values. Available at: https://mcc.ca/examinations-assessments/resources-to-help-with-exam-prep/normal-lab-values/. Last accessed April 19, 2023.
  5. NCCN Clinical Practice Guidelines in Oncology. Kidney Cancer, Version 2.2024.
  6. Motzer R et al. Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N Engl J Med. 2021;384(14):1289-1300. doi: 10.1056/NEJMoa2035716

CA-KLH-00054

Safety

Important safety information

KEYTRUDA® IMPORTANT SAFETY INFORMATION

KEYTRUDA® has been issued marketing authorization without conditions for:

  • Treatment of adult patients with advanced (not amenable to curative surgery or radiation) or metastatic RCC in combination with lenvatinib with no prior systemic therapy for metastatic RCC.
  • Treatment of adult patients with advanced endometrial carcinoma, in combination with lenvatinib, that is not microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior platinum-based systemic therapy and are not candidates for curative surgery or radiation.

 

Clinical use:

The safety and efficacy of KEYTRUDA® has not been established for pediatric patients with conditions other than relapsed or refractory cHL, or relapsed or refractory PMBCL, or melanoma (Stage IIB or IIC).

Geriatrics (>65 years of age): No overall differences in safety or efficacy were reported between elderly patients (65 years and over) and younger patients (less than 65 years) for KEYTRUDA® monotherapy. No overall differences in efficacy were reported between elderly patients (65 years and over) and younger patients (less than 65 years) for KEYTRUDA® combination therapy. Limited safety and efficacy information is available for KEYTRUDA® in cHL ≥ 65 years of age (n=20).

Relevant warnings and precautions:

  • Immune-mediated adverse reactions, including severe and fatal cases:
    • Pneumonitis
    • Colitis
    • Hepatitis
    • Nephritis and renal dysfunction
    • Endocrinopathies including adrenal insufficiency, hypophysitis, type 1 diabetes mellitus and thyroid disorders
    • Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis
  • Other immune-mediated adverse events including uveitis, arthritis, myositis, encephalitis, sarcoidosis, myasthenic syndrome/myasthenia gravis, vasculitis, Guillain-Barré syndrome, hemolytic anemia, pancreatitis, myelitis, myocarditis, hypoparathyroidism, sclerosing cholangitis, aplastic anemia, gastritis
  • Solid organ transplant rejection
  • Elevated liver enzymes when used in combination with axitinib for RCC
  • Increased mortality when used with thalidomide analogue and dexamethasone in multiple myeloma
  • Allogeneic stem cell transplant after and before treatment
  • Severe infusion-related reactions
  • Teratogenic risk
  • Women should avoid pregnancy and breastfeeding during treatment and for at least 4 months after it
  • Patients with hepatic impairment
  • Renal impairment
  • Driving and operating machinery
  • Monitoring requirements
  • Pediatrics <18 years of age
  • Geriatrics

 

For more information:

Please consult the Product Monograph for important information regarding adverse reactions, drug interactions, and dosing information which have not been discussed in this piece.

The Product Monograph is also available by calling us at 1-800-567-2594 or by email at medinfocanada@merck.com.

PD-L1=programmed death-ligand 1.

 

LENVIMA® IMPORTANT SAFETY INFORMATION

LENVIMA® (lenvatinib capsules) is indicated:

  • Renal Cell Carcinoma (RCC) in combination with pembrolizumab, for the treatment of adult patients with advanced (not amenable to curative surgery or radiation) or metastatic RCC with no prior systemic therapy for metastatic RCC.
  • Endometrial Carcinoma (EC) in combination with pembrolizumab, for the treatment of adult patients with advanced endometrial carcinoma that is not microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior platinum-based systemic therapy, and are not candidates for curative surgery or radiation.

 

Clinical use:

  • The safety and efficacy of LENVIMA® have not been established in patients < 18 years of age
  • LENVIMA® in combination with KEYTRUDA® showed a higher incidence of adverse events (Grade ≥ 3) and discontinuation in RCC patients ≥ 65 years of age than in patient <65 years of age

 

Most serious warnings & precautions:

Hypertension and its complications, including fatal artery dissection

Cardiovascular: Cardiac failure, including fatal cases

Arterial thromboembolism (ATE), including fatal cases

Gastrointestinal perforation and fistula formation, including reactions leading to death

Hepatic/Biliary/Pancreatic: Hepatotoxicity/hepatic failure, including fatal cases

Renal: Renal failure and impairment, including fatal cases. The primary risk factor identified was dehydration/hypovolemia due to diarrhea and vomiting

Hematologic: Hemorrhage, including fatal cases

Neurologic: Posterior reversible encephalopathy syndrome (PRES)

Other relevant warnings and precautions:

  • Prior anticancer treatments
  • QTc prolongation; correct electrolyte abnormalities in all patients. Avoid use with electrolyte-disrupting drugs
  • Hypocalcemia
  • Impairment of thyroid stimulating hormone suppression/thyroid dysfunction
  • Diarrhea: Initiate prompt medical management
  • Osteonecrosis of the jaw (ONJ): Consider a dental examination and preventative dentistry prior to initiating LENVIMA®. If possible, avoid invasive dental procedures. Caution is advised with agents associated with ONJ such as bisphosphonates and denosumab
  • Wound healing complications
  • Proteinuria
  • Fertility
  • Men and women of reproductive potential should use contraception
  • Caution in patients with body weight <60 kg
  • Caution in Asian and Caucasian patients
  • Monitor complete blood cell count (CBC)
  • Pregnancy: LENVIMA® should not be used during pregnancy unless necessary and based on a benefit/risk assessment of the mother and fetus
  • Breastfeeding: LENVIMA® should not be used during breastfeeding
  • Not recommended for patients with end-stage renal disease
  • Incidence of side effects may vary by gender
  • Monitoring and laboratory tests
  • When LENVIMA® is used in combination with KEYTRUDA®, see the KEYTRUDA® Product Monograph

 

For more information:

Please consult the LENVIMA® Product Monograph for important information relating to adverse reactions, drug interactions, and dosing information that has not been discussed in this piece.

The Product Monograph is also available by calling Eisai Limited at 1-877-873-4724.