ESMO: European Society for Medical Oncology; HNSCC: head and neck squamous cell carcinomaa; MDT: multidisciplinary team; NCCN: National Comprehensive Cancer Network; NSCLC: non small cell lung cancer.

KEYTRUDA® (Pembrolizumab) Selected Safety Information (SSI)

Selected indications: In combination with pemetrexed and platinum chemotherapy indicated for the first-line treatment of patients with metastatic non-squamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations. In combination with carboplatin and either paclitaxel or paclitaxel protein-bound indicated for the first-line treatment of patients with metastatic squamous NSCLC. Single-agent indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [Tumor Proportion Score (TPS) ≥1%] as determined by a validated test, with no EGFR or ALK genomic tumor aberrations, and is either stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic. Single-agent indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS≥1%) as determined by a validated test, with disease progression on or after platinum-containing chemotherapy (patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA®). Single-agent indicated for adjuvant treatment following resection and platinum-based chemotherapy for adult patients with stage IB (T2a ≥4 cm), II, or IIIA NSCLC. Treatment of patients with resectable (tumors ≥4 cm or node-positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment and then continued as a single agent as adjuvant treatment after surgery.
In combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC). As a single agent, is indicated for the first line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by a validated test. Treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.
Treatment of patients with high-risk early-stage TNBC (triple-negative breast cancer) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery. In combination with chemotherapy, for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥10] as determined by a validated test.

Dosage & Administration: KEYTRUDA® is administered 30 minutes intravenous infusion.

Monotherapy: Adjuvant treatment of adult patients with NSCLC is 200 mg every 3 weeks or 400 mg every 6 weeks until disease recurrence or unacceptable toxicity, or up to 12 months. Adult patients with NSCLCs 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression or unacceptable toxicity, or up to 24 months.
Adult patients with HNSCC is 200 mg every 3 weeks or 400 mg every 6 weeks, until disease progression or unacceptable toxicity, or up to 24 months.

Combination Therapy: Adult patients with NSCLC is 200 mg every 3 weeks or 400 mg every 6 weeks (administer KEYTRUDA® prior to chemotherapy when given on the same day), until disease progression or unacceptable toxicity, or up to 24 months. Adult patients with resectable NSCLC is 200 mg every 3 weeks or 400 mg every 6 weeks (administer KEYTRUDA® prior to chemotherapy when given on the same day), neoadjuvant treatment in combination with chemotherapy for 12 weeks or until disease progression that precludes definitive surgery or unacceptable toxicity, followed by adjuvant treatment with KEYTRUDA® as a single agent after surgery for 39 weeks or until disease recurrence or unacceptable toxicity.
Adult patients with HNSCC is 200 mg every 3 weeks or 400 mg every 6 weeks (administer KEYTRUDA® prior to chemotherapy when given on the same day), until disease progression or unacceptable toxicity, or up to 24 months.
Adult patients with locally recurrent unresectable or metastatic TNBC is 200 mg every 3 weeks or 400 mg every 6 weeks (administer KEYTRUDA® prior to chemotherapy when given on the same day), until disease progression or unacceptable toxicity, or up to 24 months.
Adult patients with high-risk early-stage TNBC is 200 mg every 3 weeks or 400 mg every 6 weeks (administer KEYTRUDA® prior to chemotherapy when given on the same day), neoadjuvant treatment in combination with chemotherapy for 24 weeks (8 doses of 200 mg every 3 weeks or 4 doses of 400 mg every 6 weeks) or until disease progression or unacceptable toxicity, followed by adjuvant treatment with KEYTRUDA® as a single agent for up to 27 weeks (9 doses of 200 mg every 3 weeks or 5 doses of 400 mg every 6 weeks) or until disease recurrence or unacceptable toxicity.

Contraindications: None

Precautions/Warnings: KEYTRUDA® can cause severe and fatal Immune-mediated Adverse Reactions which can occur in any organ, system or tissue as Immune-mediated Pneumonitis, Immune-mediated Colitis, Hepatotoxicity and Immune-mediated Hepatitis, Immune-mediated Nephritis with Renal Dysfunction, Immune-mediated Endocrinopathies (as adrenal insufficiency, hypophysitis, hyperthyroidism, hypothyroidism, thyroiditis & type 1 diabetes mellitus) & Immune-Mediated Dermatologic Adverse Reactions. KEYTRUDA® can cause other immune-mediated adverse reactions as: Myocarditis, pericarditis, vasculitis, Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy, Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis, Hypoparathyroidism, Myositis/polymyositis, rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica, Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection, Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss. KEYTRUDA® can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis. KEYTRUDA® can cause complications of Allogeneic HSCT. Increased Mortality in Patients with Multiple Myeloma when KEYTRUDA® is added to a Thalidomide Analogue and Dexamethasone. KEYTRUDA® can cause fetal harm when administered to a pregnant woman.

Adverse Reactions:
Most common adverse reactions (reported in ≥20% of patients) were:

• KEYTRUDA® as a single agent: fatigue, musculoskeletal pain, rash, diarrhea, pyrexia, cough, decreased appetite, pruritus, dyspnea, constipation, pain, abdominal pain, nausea, and hypothyroidism.
• KEYTRUDA® in combination with chemotherapy or chemoradiotherapy: fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, pyrexia, alopecia, peripheral neuropathy, mucosal inflammation, stomatitis, headache, weight loss, abdominal pain, arthralgia, myalgia, insomnia, palmar-plantar erythrodysesthesia, urinary tract infection, and hypothyroidism.

Please refer to the full prescribing information of KEYTRUDA® for more information.