biomarker testing

Important KEYTRUDA® safety information

KEYTRUDA® has been issued marketing authorization without conditions for:

HNSCC (head and neck squamous cell carcinoma)

• For the treatment of adult patients with resectable locally advanced HNSCC whose tumours express PD-L1 ([CPS] ≥ 1), as determined by a validated test, as neoadjuvant treatment as monotherapy, continued as adjuvant treatment in combination with radiotherapy (RT) with or without cisplatin and then as monotherapy
• For the first-line treatment of metastatic or unresectable recurrent HNSCC as monotherapy, in adult patients whose tumours have PD-L1 expression (CPS ≥ 1) as determined by a validated test
• For the first-line treatment of metastatic or unresectable recurrent HNSCC in combination with platinum and FU (fluorouracil) chemotherapy, in adult patients.

TNBC (triple-negative breast cancer)

• In combination with chemotherapy, for the treatment of adult patients with locally recurrent unresectable or metastatic TNBC, who have not received prior chemotherapy for metastatic disease and whose tumours express PD-L1 (CPS ≥ 10) as determined by a validated test. Consult the description of the study for the chemotherapy (paclitaxel, nab-paclitaxel, or gemcitabine/carboplatin) and dosing regimens used
• For the treatment of adult patients with high-risk early-stage TNBC in combination with chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgery. Consult the description of the study for the chemotherapy regimen (carboplatin and paclitaxel, followed by doxorubicin or epirubicin and cyclophosphamide) used

NSCLC (non-small cell lung carcinoma)

• For the first-line treatment, as monotherapy, of adult patients with metastatic NSCLC or stage III disease where patients are not candidates for surgical resection or definitive chemoradiation, expressing PD-L1 (TPS ≥ 1%) as determined by a validated test, with no EGFR or ALK genomic tumour aberrations. A positive association was observed between the level of PD-L1 expression and the magnitude of the treatment benefit.
• In combination with pemetrexed and platinum chemotherapy, for the treatment of adult patients with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumour aberrations, and no prior systemic chemotherapy treatment for metastatic NSCLC.
• In combination with carboplatin and either paclitaxel or nab-paclitaxel, for the treatment of adult patients with metastatic squamous NSCLC with no prior systemic chemotherapy treatment for metastatic NSCLC.
• As monotherapy, for the treatment of adult patients with metastatic NSCLC whose tumours express PD-L1 (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 an authorized therapy for these aberrations prior to receiving KEYTRUDA®.
• As monotherapy, for the adjuvant treatment of adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC who have undergone complete resection and platinum-based chemotherapy
• In combination with platinum-containing chemotherapy, for the treatment of adult patients with resectable Stage II, IIIA, or IIIB (T3-4N2) NSCLC, as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgery

MPM (malignant pleural mesothelioma)

• In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of adult patients with unresectable advanced or metastatic MPM

UC (urothelial carcinoma)

• In combination with enfortumab vedotin, for the treatment of adult patients with unresectable locally advanced or metastatic UC (mUC) with no prior systemic therapy for mUC
• For the treatment of adult patients with locally advanced unresectable or mUC, as monotherapy, who are not eligible for any platinum-containing chemotherapy. An improvement in survival or disease-related symptoms has not been established
• For the treatment of adult patients with locally advanced or mUC, as monotherapy, who have disease progression during or following platinum-containing chemotherapy or within 12 months of completing neoadjuvant or adjuvant platinum-containing chemotherapy

Cervical cancer

• In combination with chemoradiotherapy (CRT), for treatment of adult patients with FIGO 2014 Stage III-IVA cervical cancer.
• In combination with chemotherapy with or without bevacizumab, for the treatment of adult patients with persistent, recurrent, or metastatic cervical cancer whose tumours express PD-L1 (CPS ≥ 1) as determined by a validated test.

Melanoma

• For the 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.
• For the 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.
• For the adjuvant treatment of adult and pediatric (12 years and older) patients with Stage IIB, IIC, or III melanoma following complete resection

RCC (renal cell carcinoma)

• In combination with axitinib, for the treatment of adult patients with advanced or metastatic RCC with no prior systemic therapy for metastatic RCC.
• In combination with lenvatinib, 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.
• As monotherapy, for the adjuvant treatment of adult patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.

CRC (colorectal cancer)

• As monotherapy, for the treatment of adult patients with metastatic MSI-H (microsatellite instability high cancer) or dMMR (mismatch repair deficient) CRC as determined by a validated test

Endometrial carcinoma

• In combination with carboplatin and paclitaxel, for the treatment of adult patients with primary advanced or recurrent endometrial carcinoma, and then continued as monotherapy
• In combination with lenvatinib, for the treatment of adult patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior platinum-based systemic therapy, and are not candidates for curative surgery or radiation.

Esophageal cancer

• In combination with platinum and fluoropyrimidine based chemotherapy, for the first-line treatment of adult patients with locally advanced unresectable or metastatic carcinoma of the esophagus.

Gastric cancer or GEJ (gastroesophageal junction) adenocarcinoma

• In combination with trastuzumab, fluoropyrimidine- and platinum- containing chemotherapy, for the first-line treatment of adult patients with locally advanced unresectable or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumours express PD-L1 (CPS ≥ 1) as determined by a validated test.
• in combination with fluoropyrimidine- and platinum-containing chemotherapy,for the first-line treatment of adult patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.

MSI-H (microsatellite instability high) or mismatch repair deficient (dMMR) cancer

• As monotherapy, for the treatment of adult and pediatric patients with unresectable or metastatic MSI-H or dMMR solid tumours, as determined by a validated test, that have progressed following prior treatment and who have no satisfactory alternative treatment options

BTC (biliary tract cancer)

• For the treatment of adult patients with locally advanced unresectable or metastatic biliary tract carcinoma (BTC), in combination with gemcitabine-based chemotherapy

Important safety information 

Clinical use:

The safety and efficacy of KEYTRUDA® has not been established for pediatric patients with conditions other than melanoma (Stage IIB, IIC, or III), relapsed or refractory cHL, relapsed or refractory PMBCL, or unresectable or metastatic MSI-H or dMMR solid tumours. 

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:
  • 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, hypoparathyroidism, gastritis, pericarditis, myocarditis, sclerosing cholangitis, aplastic anemia, and exocrine pancreatic insufficiency
• Solid organ transplant rejection
• Use in combination with axitinib for RCC
• Use with thalidomide analogue and dexamethasone in multiple myeloma
• Allogeneic stem cell transplant after and before treatment
• Severe infusion-related reactions
• Teratogenic toxicity
• Women of childbearing potential should use highly effective contraception and take active measures to avoid pregnancy during treatment and for at least 4 months after the last dose  
• Advise women not to breastfeed during treatment and for at least 4 months after the last dose  
• Patients with hepatic impairment 
• Renal impairment
• Driving and operating machinery
• Monitoring requirements
• Pediatrics
• Geriatrics