KEYTRUDA® is indicated with conditions for:

Adult patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer whose tumours have progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, as monotherapy.  

KEYTRUDA® has been issued conditional marketing authorization pending the results of studies to verify its clinical benefit. Patients should be advised of this conditional marketing authorization. For further information for Keytruda, please refer to Health Canada’s Notice of Compliance with conditions drug products website: https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/notice-compliance/conditions.html.

KEYTRUDA® is indicated without conditions for:

In the first-line setting, as monotherapy for adult patients with metastatic microsatellite instability (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC)

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®*) for Colon and Rectal Cancer
Systemic therapy recommendations for advanced or metastatic cancer.4,5 

Colon cancer:

  • Pembrolizumab is recommended as a preferred option as an initial therapy for advanced or metastatic disease (dMMR/MSI-H only) 

Rectal cancer

  • Pembrolizumab is recommended as a preferred option as an initial therapy for advanced or metastatic disease (dMMR/MSI-H only)

Read more about the NCCN Guideline recommendations for colon and rectal cancer.

Are you testing all your patients with metastatic colorectal cancer for MSI-H/dMMR?

Patients with metastatic CRC can be selected for treatment based on MSI-H or dMMR tumour-positive status as determined by an accredited lab using validated testing methods1

Biomarker analyses in colorectal cancer

The MMR system is responsible for the detection and correction of DNA errors that arise during cell division. A dysfunctional MMR system may arise through various means, and leads to microsatellite instability.2

Microsatellite instability (MSI)

  • Identified through PCR3
    • Compares the length of nucleotide repeats in tumour cells and normal cells2
  • Is available on-site at most institutions

Mismatch repair (MMR)

  • Identified through IHC3
    • Detects the presence and absence of MMR protein expression2
  • Is available on-site at most institutions

Clinical Studies

KEYNOTE-177 trial: Evaluating KEYTRUDA® monotherapy in the first-line setting for metastatic MSI-H/dMMR CRC

 

KEYNOTE-177 trial

KEYNOTE-164 trial: Evaluating KEYTRUDA® monotherapy after prior therapy in metastatic MSI-H/dMMR CRC

 

KEYNOTE-164 trial

Flexible dosing with KEYTRUDA®1

Recommended dosing regimens in previously untreated metastatic dMMR or MSI-H colorectal carcinoma is a 30-minute IV infusion that can be given as 200 mg every 3 weeks or 400 mg every 6 weeks†. 

Continue until disease progression, unacceptable toxicity, or up to 24 months or 35 doses for 200 mg or 18 doses for 400 mg, whichever is longer, in patients without disease progression.

Let patients know that they have two options for KEYTRUDA® dosing, and discuss which regimen is right for them. Learn more about KEYTRUDA® flexible dosing.

Learn More

*NCCN Guidelines is a trademark of National Comprehensive Cancer Network, Inc
† Patients appropriate for intensive therapy should be followed closely for 10 weeks to assess response.
# If disease response, consider discontinuing checkpoint inhibitors after 2 years of treatment.
‡ If no previous treatment with a checkpoint inhibitor.

References:

  1. 1. KEYTRUDA® Product Monograph. Merck Canada Inc. April 19, 2023.
  2. 2. Mayo Clinic. Microsatellite Instability, Tumor. Available at: https://www.mayocliniclabs.com/test-catalog/Overview/609364. Accessed February 14, 2022. 
  3. 3. College of American Pathologists. POET Report: Prognostic Uses of MSI Testing. Available at: https://webapps.cap.org/apps/docs/committees/technology/microsatellite_testing.pdf. Accessed February 14, 2022.
  4. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer V1.2022. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed April 11, 2022.
  5. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Rectal Cancer V1.2022. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed April 11, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org. 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.

CA-OVA-00054

Consider KEYTRUDA® for your patients with metastatic MSI-H/dMMR colorectal cancer

Learn more by reviewing our patient profiles
Safety

Important safety information

KEYTRUDA® has been issued marketing authorization with conditions, pending the results of trials to verify its clinical benefit. Patients should be advised of the nature of the authorization.

KEYTRUDA® is indicated for:

  • Treatment, as monotherapy, of adult and pediatric patients with refractory or relapsed classical Hodgkin Lymphoma (cHL) who have failed autologous stem cell transplant (ASCT), or who are not candidates for multi-agent salvage chemotherapy and ASCT. An improvement in overall survival has not yet been established.
  • Treatment, as monotherapy, of adult and pediatric patients with refractory primary mediastinal B-cell lymphoma (PMBCL), or who have relapsed after 2 or more lines of therapy. An improvement in survival or disease-related symptoms has not been established.
  • Treatment of adult patients with locally advanced unresectable or metastatic urothelial carcinoma, as monotherapy who are not eligible for cisplatin-containing chemotherapy and whose tumours express PD-L1 [Combined Positive Score (CPS) ≥10] as determined by a validated test, or in adults who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. An improvement in survival or disease-related symptoms has not been established. 
  • Treatment of adult patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in-situ (CIS) with or without papillary tumours who are ineligible for or have elected not to undergo cystectomy. The indication is authorized based on tumour complete response rate and durability of response.
  • Treatment, as monotherapy, of adult patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) for:
    • colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan; or
    • endometrial cancer that has progressed following prior therapy and who have no satisfactory alternative treatment options.
  • Treatment of adult patients in combination with lenvatinib 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.

KEYTRUDA® has been issued marketing authorization without conditions for: 

  • Treatment of adult patients with unresectable or metastatic melanoma who have not received prior treatment with ipilimumab. Subjects with BRAF V600 mutant melanoma may have received prior BRAF inhibitor therapy.
  • Treatment of adult patients with unresectable or metastatic melanoma and disease progression following ipilimumab therapy and, if BRAF V600 mutation positive, following a BRAF or MEK inhibitor.
  • Adjuvant treatment of adult and pediatric (12 years and older) patients with Stage IIB or IIC melanoma following complete resection.
  • Adjuvant treatment of adult patients with stage III melanoma with lymph node involvement who have undergone complete resection.
  • First-line treatment, as monotherapy, of adult patients with metastatic non-small cell lung carcinoma (NSCLC) or stage III disease where patients are not candidates for surgical resection or definitive chemoradiation, expressing PD-L1 [Tumour Proportion Score (TPS ≥1%)] as determined by a validated test, with no EGFR or ALK genomic tumour aberrations. 
  • Treatment of adult patients with metastatic non-squamous NSCLC in combination with pemetrexed and platinum chemotherapy, with no EGFR or ALK genomic tumour aberrations, and no prior systemic chemotherapy treatment for metastatic NSCLC.
  • Treatment of adult patients with metastatic squamous NSCLC in combination with carboplatin and either paclitaxel or nab-paclitaxel, with no prior systemic chemotherapy treatment for metastatic NSCLC.
  • Treatment of adult patients with metastatic NSCLC as monotherapy, whose tumours express PD-L1 [(Tumour Proportion Score (TPS) ≥1%)] as determined by a validated test and who have disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumour aberrations should have received authorized therapy for these aberrations prior to receiving KEYTRUDA®.
  • Adjuvant treatment of adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC whohave undergone complete resection and platinum-based chemotherapy.
  • Treatment of adult patients with locally advanced or metastatic urothelial carcinoma, as monotherapy, who have disease progression during or following platinum-containing chemotherapy or within 12 months of completing neoadjuvant or adjuvant platinum-containing chemotherapy.
  • Treatment of adult patients with advanced or metastatic renal cell carcinoma (RCC) in combination with axitinib, with no prior systemic therapy for metastatic RCC. 
  • 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.
  • Adjuvant treatment, as monotherapy, of adult patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. 
  • First-line treatment of metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) as monotherapy, in adult patients whose tumours have PD-L1 expression [Combined Positive Score (CPS) ≥ 1] as determined by a validated test.
  • First-line treatment of metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) in combination with platinum and fluorouracil (FU) chemotherapy, in adult patients. 
  • First-line treatment of adult patients with metastatic MSI-H or dMMR colorectal cancer (CRC). 
  • First-line treatment, in combination with platinum and fluoropyrimidine based chemotherapy, of adult patients with locally advanced unresectable or metastatic carcinoma of the esophagus or HER2 negative adenocarcinoma of the esophagogastric junction (tumour centre 1 to 5 centimetres above the gastric cardia). 
  • Treatment of adult patients with persistent, recurrent, or metastatic cervical cancer whose tumours express PD-L1 (CPS ≥ 1) as determined by a validated test, in combination with chemotherapy with or without bevacizumab.
  • Treatment of adult patients with high-risk, early-stage, triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgery.
  • Treatment of adult patients in combination with chemotherapy with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC), who have not received prior chemotherapy for metastatic disease and whose tumors express PD-L1 (Combined Positive Score [CPS] ≥10), as determined by a validated test 

 

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). 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
  • 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 hematopoietic stem cell transplant after and before treatment
  • Severe infusion-related reactions
  • Teratogenic risk toxicity 
  • 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.