KEYTRUDA

Therapy must be initiated and supervised by specialist physicians experienced in the treatment of cancer. Patients receiving intravenous pembrolizumab can switch to subcutaneous pembrolizumab at their next scheduled dose. Patients receiving subcutaneous pembrolizumab can switch to intravenous pembrolizumab at their next scheduled dose.

1). 1). Posology The recommended dose of KEYTRUDA solution for injection in adults is either: - 395 mg every 3 weeks administered as a subcutaneous injection over 1 minute or - 790 mg every 6 weeks administered as a subcutaneous injection over 2 minutes.

KEYTRUDA solution for injection is available in another strength. 6. For use in combination, see the Summary of Product Characteristics (SmPC) for the concomitant therapies. Patients should be treated with KEYTRUDA until disease progression or unacceptable toxicity (and up to maximum duration of therapy if specified for an indication).

, 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 4 doses of 395 mg every 3 weeks or 2 doses of 790 mg every 6 weeks or until disease progression that precludes definitive surgery or unacceptable toxicity, followed by adjuvant treatment with KEYTRUDA as monotherapy for 13 doses of 395 mg every 3 weeks or 7 doses of 790 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.

For the neoadjuvant and adjuvant treatment of resectable locally advanced HNSCC, patients should be treated with neoadjuvant KEYTRUDA as monotherapy for 2 doses of 395 mg every 3 weeks or 1 dose of 790 mg or until disease progression that precludes definitive surgery or unacceptable toxicity, followed by adjuvant treatment with KEYTRUDA in combination with radiation with or without concomitant cisplatin for 3 doses of 395 mg every 3 weeks or 2 doses of 790 mg every 6 weeks followed by KEYTRUDA as monotherapy for 12 doses of 395 mg every 3 weeks or 6 doses of 790 mg every 6 weeks or until disease recurrence or unacceptable toxicity.

Summary of the safety profile Pembrolizumab is most commonly associated with immune-mediated adverse reactions. Most of these, including severe reactions, resolved following initiation of appropriate medical therapy or withdrawal of pembrolizumab (see “Description of selected adverse reactions” below).

The frequencies included below and in Table 2 are based on all reported adverse drug reactions, regardless of the investigator assessment of causality. 4% in the subcutaneous pembrolizumab arm), which were all Grade 1. 2) The safety of intravenous pembrolizumab as monotherapy has been evaluated in 7 631 patients across tumour types and across four doses (2 mg/kg bw every 3 weeks, 200 mg every 3 weeks, or 10 mg/kg bw every 2 or 3 weeks) in clinical studies.

5 months (range: 1 day to 39 months) and the most frequent adverse reactions with pembrolizumab were fatigue (31%), diarrhoea (22%), and nausea (20%). The majority of adverse reactions reported for monotherapy were of Grades 1 or 2 severity.

4). The incidences of immune-mediated adverse reactions were 37% all Grades and 9% for Grades 3-5 for pembrolizumab monotherapy in the adjuvant setting and 25% all Grades and 6% for Grades 3-5 in the metastatic setting. No new immune-mediated adverse reactions were identified in the adjuvant setting.

2) When pembrolizumab is administered in combination, refer to the SmPC for the respective combination therapy components prior to initiation of treatment. The safety of intravenous pembrolizumab in combination with chemotherapy, RT or CRT has been evaluated in 6 695 patients across tumour types receiving 200 mg, 2 mg/kg bw or 10 mg/kg bw pembrolizumab every 3 weeks, in clinical studies.

In this patient population, the most frequent adverse reactions were anaemia (50%), nausea (51%), diarrhoea (35%), fatigue (35%), constipation (32%), vomiting (27%), neutrophil count decreased (26%), and decreased appetite (26%). Incidences of Grades 3-5 adverse reactions in patients with NSCLC were 69% for pembrolizumab combination therapy and 61% for chemotherapy alone, in patients with HNSCC were 80% for pembrolizumab combination therapy (chemotherapy or RT with or without chemotherapy), and 79% for chemotherapy plus cetuximab or RT with or without chemotherapy, in patients with oesophageal carcinoma were 86% for pembrolizumab combination therapy and 83% for chemotherapy alone, in patients with TNBC were 80% for pembrolizumab combination therapy and 77% for chemotherapy alone, in patients with cervical cancer were 77% for pembrolizumab combination therapy (chemotherapy with or without bevacizumab or in combination with CRT) and 71% for chemotherapy with or without bevacizumab or CRT alone, in patients with gastric cancer were 74% for pembrolizumab combination therapy (chemotherapy with or without trastuzumab) and 68% for chemotherapy with or without trastuzumab, in patients with biliary tract carcinoma were 85% for pembrolizumab combination therapy and 84% for chemotherapy alone, and in patients with EC were 59% for pembrolizumab combination therapy and 46% for chemotherapy alone.

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Assessment of PD-L1 status When assessing the PD-L1 status of the tumour, it is important that a well-validated and robust methodology is chosen to minimise false negative or false positive determinations.

Immune-mediated adverse reactions Immune-mediated adverse reactions, including severe and fatal cases, have occurred in patients receiving pembrolizumab. Most immune-mediated adverse reactions occurring during treatment with pembrolizumab were reversible and managed with interruptions of pembrolizumab, administration of corticosteroids and/or supportive care.

Immune-mediated adverse reactions have also occurred after the last dose of pembrolizumab. Immune-mediated adverse reactions affecting more than one body system can occur simultaneously. For suspected immune-mediated adverse reactions, adequate evaluation to confirm aetiology or exclude other causes should be ensured.

Based on the severity of the adverse reaction, pembrolizumab should be withheld and corticosteroids administered. Upon improvement to Grade ≤ 1, corticosteroid taper should be initiated and continued over at least 1 month. Based on limited data from clinical studies in patients whose immune-mediated adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered.

Pembrolizumab may be restarted within 12 weeks after last dose of KEYTRUDA if the adverse reaction recovers to Grade ≤ 1 and corticosteroid dose has been reduced to ≤ 10 mg prednisone or equivalent per day. 8). In patients with pre-existing autoimmune disease (AID), data from observational studies suggest that the risk of immune-mediated adverse reactions following immune-checkpoint inhibitor therapy may be increased as compared with the risk in patients without pre-existing AID.

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