HNSCC -test

Indications:
Melanoma: KEYTRUDA as monotherapy is indicated for the treatment of adults and adolescents aged 12 years and older with advanced (unresectable or metastatic) melanoma. KEYTRUDA as monotherapy is indicated for the adjuvant treatment of adults and adolescents aged 12 years and older with Stage IIB, IIC or III melanoma and who have undergone complete resection.
Non-small cell lung carcinoma (NSCLC): KEYTRUDA as monotherapy is indicated for the first-line treatment of metastatic nonsmall cell lung carcinoma in adults whose tumours express PD-L1 with a ≥ 50% tumour proportion score (TPS) with no EGFR or ALK positive tumour mutations. KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of metastatic non-squamous non-small cell lung carcinoma in adults whose tumours have no EGFR or ALK
positive mutations. KEYTRUDA, in combination with carboplatin and either paclitaxel or nab-paclitaxel, is indicated for the firstline treatment of metastatic squamous non-small cell lung carcinoma in adults. KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic non-small cell lung carcinoma in adults whose tumours express PD-L1 with a ≥ 1% TPS and who have received at least one prior chemotherapy regimen. Patients with EGFR or ALK positive tumour mutations should also have received targeted therapy before receiving KEYTRUDA. KEYTRUDA is indicated for the 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 monotherapy as adjuvant treatment after surgery. KEYTRUDA, as monotherapy is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.
Classical Hodgkin lymphoma (cHL): KEYTRUDA as monotherapy is indicated for the treatment of adult and paediatric patients aged 3 years and older with relapsed or refractory classical Hodgkin lymphoma who have failed autologous stem cell transplant (ASCT) or following at least two prior therapies when ASCT is not a treatment option.
Urothelial carcinoma: KEYTRUDA, in combination with enfortumab vedotin, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma. KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who have received prior platinum-containing chemotherapy. KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy. This indication was approved based on complete response rate and duration of response. Continued approval of this indication depends on verification and description of benefit in confirmatory trials.
Head and neck squamous cell carcinoma (HNSCC): KEYTRUDA, as monotherapy or in combination with platinum and 5-fluorouracil (5-FU) chemotherapy, is indicated for the first-line treatment of metastatic or unresectable recurrent head and neck squamous cell carcinoma in adults whose tumours express PD L1 with a CPS ≥ 1. KEYTRUDA as monotherapy is indicated for the treatment of recurrent or metastatic head and neck squamous cell carcinoma in adults whose tumours express PD-L1 with a ≥ 50% TPS and progressing on or after platinum-containing chemotherapy.
Renal cell carcinoma (RCC): KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of advanced renal cell carcinoma in adults. KEYTRUDA, in combination with lenvatinib, is indicated for the first-line treatment ofadvanced renal cell carcinoma in adults. KEYTRUDA as monotherapy is indicated for the adjuvant treatment of adults with renal cell carcinoma at increased risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
Microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) cancers
Colorectal cancer (CRC): KEYTRUDA as monotherapy is indicated for adults with MSI-H or dMMR colorectal cancer in the following settings:

Non-colorectal cancers: KEYTRUDA as monotherapy is indicated for the treatment of the following MSI-H or dMMR tumours in adults with:

Gastric or gastro-oesophageal junction (GEJ) adenocarcinoma: KEYTRUDA, in combination with trastuzumab, fluoropyrimidine and platinum-containing chemotherapy, is indicated for the first-line treatment of locally advanced unresectable or metastatic HER2-positive gastric or gastro-oesophageal junction adenocarcinoma in adults whose tumours express PD-L1 with a CPS ≥ 1 as determined by a validated test.
Oesophageal carcinoma: KEYTRUDA, in combination with platinum and fluoropyrimidine-based chemotherapy, is indicated for the first-line treatment of locally advanced unresectable or metastatic carcinoma of the oesophagus or HER-2 negative gastroesophageal junction adenocarcinoma, in adults whose tumours express PD-L1 with a CPS ≥ 10.
Triple-negative breast cancer (TNBC): KEYTRUDA, in combination with chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgery, is indicated for the treatment of adults with locally advanced, or early-stage triple-negative breast cancer at high risk of recurrence. KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of locally recurrent unresectable or metastatic triple-negative breast cancer in adults whose tumours express PD-L1 with a CPS ≥ 10 and who have not received prior chemotherapy for metastatic disease.
Endometrial carcinoma (EC): KEYTRUDA, in combination with lenvatinib, is indicated for the treatment of adult patients with advanced endometrial carcinoma that is mismatch repair proficient (pMMR) or not MSI-H, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Cervical cancer: KEYTRUDA, in combination with chemotherapy with or without bevacizumab, is indicated for the treatment of persistent, recurrent, or metastatic cervical cancer in adults whose tumours express PD-L1 with a CPS ≥ 1.

Posology:
The recommended dose of KEYTRUDA in adults is either 200 mg every 3 weeks or 400 mg every 6 weeks administered as an intravenous infusion over 30 minutes.

The recommended dose of KEYTRUDA as monotherapy in paediatric patients aged 3 years and older with cHL or patients aged 12 years and older with melanoma is 2 mg/kg bodyweight (bw) (up to a maximum of 200 mg), every 3 weeks administered as an intravenous infusion over 30 minutes.

For use in combination, see the Summary of Product Characteristics (SmPC) for the concomitant therapies.

For urothelial carcinoma patients treated with KEYTRUDA in combination with enfortumab vedotin, administer KEYTRUDA after enfortumab vedotin when given on the same day.

For urothelial carcinoma patients treated with KEYTRUDA in combination with enfortumab vedotin, the recommended initial dose of enfortumab vedotin is 1.25 mg/kg (up to a maximum of 125 mg for patients ≥100 kg) as an intravenous solution on Days 1 and 8 of a 21-day cycle until disease progression or unacceptable toxicity.

Patients should be treated with KEYTRUDA until disease progression or unacceptable toxicity (and up to maximum duration of therapy if specified for an indication). Atypical responses (i.e. an initial transient increase in tumour size or small new lesions within the first few months followed by tumour shrinkage) have been observed. It is recommended to continue treatment for clinically stable patients with initial evidence of disease progression until disease progression is confirmed.

For the adjuvant treatment of melanoma, NSCLC, or RCC, KEYTRUDA should be administered until disease recurrence, unacceptable toxicity, or for a duration of up to one year.

For the neoadjuvant and adjuvant treatment of resectable NSCLC, patients should be treated with neoadjuvant KEYTRUDA 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 monotherapy for 39 weeks or until disease recurrence or unacceptable toxicity.

For the neoadjuvant and adjuvant treatment of TNBC, patients should be treated with neoadjuvant KEYTRUDA in combination with chemotherapy for 8 doses of 200 mg every 3 weeks or 4 doses of 400 mg every 6 weeks or until disease progression that precludes definitive surgery or unacceptable toxicity, followed by adjuvant treatment with KEYTRUDA as monotherapy for 9 doses of 200 mg every 3 weeks or 5 doses of 400 mg every 6 weeks or until disease recurrence or unacceptable toxicity. Patients who experience disease progression that precludes definitive surgery or unacceptable toxicity related to KEYTRUDA as neoadjuvant treatment in combination with chemotherapy should not receive KEYTRUDA monotherapy as adjuvant treatment.

Contraindications: Hypersensitivity to the active substance or to any of the excipients.

Precautions/Warnings: KEYTRUDA can cause Immune- mediated adverse reactions, including severe and fatal cases. Immune-mediated Pneumonitis, Immune-mediated Colitis, Immune-mediated Hepatitis, Immune-mediated Nephritis, Immune-mediated Endocrinopathies (as adrenal insufficiency, hypophysitis, type 1 diabetes mellitus, diabetic ketoacidosis, hypothyroidism, and hyperthyroidism) & Immune-mediated Skin adverse reactions. KEYTRUDA can cause other immunemediated adverse reactions as: uveitis, arthritis, myositis, myocarditis, pancreatitis, Guillain-Barré syndrome, myasthenic syndrome, haemolytic anaemia, sarcoidosis, encephalitis, myelitis, vasculitis, cholangitis sclerosing, gastritis, cystitis noninfective and hypoparathyroidism. KEYTRUDA can cause severe infusion-related reactions including hypersensitivity and anaphylaxis. Solid organ transplant rejection has been reported in the post-marketing setting in patients treated with PD-1 inhibitors. Cases of graft-versus-host disease (GVHD) and hepatic veno-occlusive disease (VOD) have been observed in patients with cHL undergoing allogeneic HSCT after previous exposure to KEYTRUDA. In patients with a history of allogeneic HSCT, acute GVHD, including fatal GVHD, has been reported after treatment with KEYTRUDA. KEYTRUDA should not be used during pregnancy unless the clinical condition of the woman requires treatment with KEYTRUDA.

Most common adverse events:
Monotherapy: anemia, hypothyroidism, decreased appetite, headache, dyspnea, cough, diarrhea, abdominal pain, nausea, vomiting, constipation, pruritus, rash, musculoskeletal pain, arthralgia, fatigue, asthenia, oedema, pyrexia.
In combination with chemotherapy: neutropenia, anemia, thrombocytopenia, hypothyroidism, hypokalemia, decreased appetite, insomnia, neuropathy peripheral, headache, dyspnea, cough, nausea, diarrhea, vomiting, abdominal pain, constipation, alopecia, rash, pruritus, arthralgia, musculoskeletal pain, myositis, fatigue, asthenia, pyrexia, alanine aminotransferase increased, aspartate aminotransferase increased.
In combination with Axitinib or Lenvatinib: anemia, hypothyroidism, decreased appetite, headache, dysgeusia, hypertension, dyspnea, cough, diarrhea, abdominal pain, nausea, vomiting, constipation, rash, pruritus, arthralgia, musculoskeletal pain, myositis, pain in extremity, fatigue, asthenia, oedema, pyrexia, lipase increased, alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased.

Please refer to the full Summary of Product Characteristics (SmPC) of KEYTRUDA® for more information