Keytruda PSP Safety

IMPORTANT SAFETY INFORMATION

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, IIC, or III melanoma following 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 (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 who have undergone complete resection and platinum-based chemotherapy.
• 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.
• 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 unresectable locally advanced or metastatic urothelial cancer (mUC), in combination with enfortumab vedotin, with no prior systemic therapy for mUC.
• 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.
• Treatment, as monotherapy, of adult patients with metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC) as determined by a validated test.
• Treatment, as monotherapy, of adult and pediatric patients with unresectable or 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.

• Treatment, in combination with lenvatinib, 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.
• 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 HNSCC in combination with platinum and fluorouracil (FU) chemotherapy, in adult patients.
• First-line treatment, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, 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.
• First-line treatment, in combination with fluoropyrimidine- and platinum-containing chemotherapy, of adult patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma.
• First-line treatment, in combination with platinum and fluoropyrimidine based chemotherapy, of adult patients with locally advanced unresectable or metastatic carcinoma of the esophagus.
• Treatment, in combination with chemotherapy, of adult patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC), who have not received prior chemotherapy for metastatic disease and whose tumours express PD-L1 (CPS ≥10), as determined by a validated test.
• 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.
• 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, in combination with gemcitabine-based chemotherapy, of adult patients with locally advanced unresectable or metastatic biliary tract carcinoma (BTC).

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:

• 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, 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

For more information:

Consult the KEYTRUDA® 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.

ALK=anaplastic lymphoma kinase; BRAF=v-raf murine sarcoma viral oncogene homologue B1; EGFR=epidermal growth factor receptor; PD-L1=programmed death ligand 1; PMBCL=primary mediastinal large B-cell lymphoma.