>> These results indicate a potential risk, based on its mechanism of action, that administration of pembrolizumab during pregnancy could cause foetal harm, including increased rates of abortion or stillbirth. See MHRA Guidance Mar 2018: Valproate use by women and girls and MHRA Valproate Pregnancy Prevention Programme toolkit for full details. Randomisation was stratified by chemotherapy treatment (paclitaxel or nab-paclitaxel vs. gemcitabine and carboplatin), tumour PD-L1 expression (CPS 1 vs. CPS < 1), and prior treatment with the same class of chemotherapy in the neoadjuvant setting (yes vs. no). * With additional 12 months of follow-up after the pre-specified final analysis for PFS. Paclitaxel 175 mg/m2 + carboplatin AUC 5 mg/mL/min, 4. Fifteen percent of patients had disease progression following prior platinum-containing neoadjuvant or adjuvant chemotherapy. direct to the MHRA on a Yellow Card , available at pharmacies, GP surgeries or from the Yellow Card hotline (freephone 0808 100 3352 during business hours). BRAF mutations were reported in 302 (36%) patients. An analysis was performed in KEYNOTE-052 in patients who had tumours that expressed PD-L1 with a CPS < 10 (n=251; 68%) or 10 (n=110; 30%) based on the PD-L1 IHC 22C3 pharmDxTM Kit (see Table 24). Table 6: Efficacy results by BRAF mutation status in KEYNOTE-002, * Hazard ratio (pembrolizumab compared to chemotherapy) based on the stratified Cox proportional hazard model. Participants with clinically stable disease, defined as disease not requiring significant change in therapy or hospitalisation for worsening disease during the 4 weeks before enrolment were included. Patients were randomised (2:1) to receive either pembrolizumab or placebo via intravenous infusion: o Four cycles of neoadjuvant pembrolizumab 200 mg every 3 weeks or placebo on Day 1 of cycles 1-4 of treatment regimen in combination with: AUC 5 mg/mL/min every 3 weeks on Day 1 of cycles 1-4 of treatment regimen or AUC 1.5 mg/mL/min every week on Day 1, 8, and 15 of cycles 1-4 of treatment regimen and, Paclitaxel 80 mg/m2 every week on Day 1, 8, and 15 of cycles 1-4 of treatment regimen. Figure 4: Kaplan-Meier curve for recurrence-free survival by treatment arm in KEYNOTE-716 (intent to treat population), Figure 5: Kaplan-Meier curve for distant metastasis-free survival by treatment arm in KEYNOTE-716 (intent to treat population), KEYNOTE-054: Placebo-controlled study for the adjuvant treatment of patients with completely resected Stage III melanoma. >> Counsel patient to report side effects from amiodarone treatment and to protect skin from sunlight. Date of first authorisation/renewal of the authorisation 10. Cisplatin could be administered on Day 2 of each 3-week treatment cycle. A Periodic Safety Update Report (PSUR) is a document which provides an evaluation of the risk-benefit balance of the medicine at defined times following authorisation. No case of overdose has been reported. Seventy-six percent of patients received 2 or more prior lines of therapy. These SPC applications are geographically-limited to Northern Ireland, unless/until a separate authorisation is also issued by the MHRA to cover the remainder of the UK, i.e. The study demonstrated a statistically significant improvement in pCR rate difference at its pre-specified primary analysis (n=602), the pCR rates were 64.8% (95% CI: 59.9%, 69.5%) in the pembrolizumab arm and 51.2 % (95% CI: 44.1%, 58.3%) in the placebo arm, with a treatment difference of 13.6 % (95% CI: 5.4%, 21.8%; p-Value 0.00055). Based on Kaplan-Meier estimation, Figure 16: Kaplan-Meier curve for progression-free survival by treatment arm in cHL patients who failed a transplant before enrolling or who failed 2 or more prior therapies and were ineligible for ASCT in KEYNOTE-204, KEYNOTE-087 and KEYNOTE-013: Open-label studies in patients with relapsed or refractory cHL. Hazard ratio (pembrolizumab combination therapy compared to chemotherapy) based on the stratified Cox proportional hazard model. Severe endocrinopathies, including adrenal insufficiency, hypophysitis, type 1 diabetes mellitus, diabetic ketoacidosis, hypothyroidism, and hyperthyroidism have been observed with pembrolizumab treatment. Approval date: September 2019, updated December 2019 Review date: December 2021 (or earlier if indicated) South East London Area Prescribing Committee. Table 12 summarises key efficacy measures for the entire intent to treat (ITT) population. Patients with autoimmune disease that required systemic therapy within 2 years of treatment or a medical condition that required immunosuppression were ineligible. Based on the severity of the adverse reaction, pembrolizumab should be withheld for Grade 3 skin reactions until recovery to Grade 1 or permanently discontinued for Grade 4 skin reactions, and corticosteroids should be administered (see section 4.2). The benefit of treatment with pembrolizumab versus the risk of possible organ rejection should be considered in these patients. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. The majority of adverse reactions reported for monotherapy were of Grades 1 or 2 severity. Use of pembrolizumab for adjuvant treatment of patients with melanoma. endstream Table 25: Response to pembrolizumab 200 mg every 3 weeks or chemotherapy in patients with previously untreated urothelial carcinoma for whom carboplatin rather than cisplatin was selected by the investigator as the better choice of chemotherapy in KEYNOTE-361, Patients who received prior therapy for melanoma other than surgery or interferon for thick primary melanomas without evidence of lymph node involvement were ineligible. Colitis led to discontinuation of pembrolizumab in 48 (0.6%) patients. For patients who completed 24 months of therapy or had a complete response, treatment with pembrolizumab could be reinitiated for disease progression and administered for up to 1 additional year. Table 2: Adverse reactions in patients treated with pembrolizumab*, In combination with axitinib or lenvatinib, neutropenia, anaemia, thrombocytopenia, leukopenia, thrombocytopenia, neutropenia, lymphopenia, neutropenia, thrombocytopenia, lymphopenia, leukopenia, leukopenia, immune thrombocytopenia, eosinophilia, haemolytic anaemia, pure red cell aplasia, haemophagocytic lymphohistiocytosis, haemolytic anaemia, immune thrombocytopenia, adrenal insufficiencyc, thyroiditisd, hyperthyroidisme, adrenal insufficiencyc, hyperthyroidism, thyroiditisd, adrenal insufficiencyc, hypophysitisf, thyroiditisd, hyponatraemia, hypokalaemia, hypocalcaemia, neuropathy peripheral, headache, dizziness, dysgeusia, dizziness, neuropathy peripheral, lethargy, dysgeusia, dizziness, neuropathy peripheral, lethargy, Guillain-Barr syndromej, encephalitisi, myelitisk, meningitis (aseptic)l, Guillain-Barr syndromej, myasthenic syndrome, cardiac arrhythmia (including atrial fibrillation), myocarditis, pericardial effusion, pericarditis, myocarditisn, pericardial effusion, pericarditis, Respiratory, thoracic and mediastinal disorders, diarrhoea, abdominal painq, nausea, vomiting, constipation, nausea, diarrhoea, vomiting, abdominal painq, constipation, colitisr, pancreatitiss, gastritis, dry mouth, pancreatitiss, gastritis, gastrointestinal ulcerationt, pancreatitiss, gastrointestinal ulcerationt, severe skin reactionsy, erythema, dermatitis, dry skin, vitiligoz, eczema, alopecia, dermatitis acneiform, severe skin reactionsy, erythema, dermatitis acneiform, dermatitis, dry skin, eczema, severe skin reactionsy, dermatitis, dry skin, erythema, dermatitis acneiform, alopecia, psoriasis, lichenoid keratosisaa, papule, hair colour changes, psoriasis, lichenoid keratosisaa, vitiligoz, papule, eczema, lichenoid keratosisaa, psoriasis, vitiligoz, papule, hair colour changes, Stevens-Johnson syndrome, erythema nodosum, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema nodosum, hair colour changes, toxic epidermal necrolysis, Stevens-Johnson syndrome, Musculoskeletal and connective tissue disorders, arthralgia, musculoskeletal painbb, myositiscc, arthralgia, musculoskeletal painbb, myositiscc, pain in extremity, myositiscc, pain in extremity, arthritisdd, General disorders and administration site conditions, alanine aminotransferase increased, aspartate aminotransferase increased, lipase increased, alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased, alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, hypercalcaemia, blood bilirubin increased, blood creatinine increased, blood creatinine increased, blood alkaline phosphatase increased, hypercalcaemia, blood bilirubin increased, amylase increased, blood bilirubin increased, blood alkaline phosphatase increased, hypercalcaemia. Clinically stable patients with initial evidence of disease progression were permitted to remain on treatment until disease progression was confirmed. Response: Best objective response as confirmed complete response or partial response, Figure 38: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-826 patients with PD-L1 expression (CPS 1), * Chemotherapy (paclitaxel and cisplatin or paclitaxel and carboplatin) with or without bevacizumab, Figure 39: Kaplan-Meier curve for progression free survival by treatment arm in KEYNOTE-826 patients with PD-L1 expression (CPS 1). Any unused medicinal product or waste material should be disposed of in accordance with local requirements. KEYTRUDA in combination with axitinib in RCC. Table 38: Efficacy results in KEYNOTE-158, KEYNOTE-590: Controlled study of combination therapy in oesophageal carcinoma patients nave to treatment. The study demonstrated a statistically significant improvement in OS and PFS for all pre-specified study populations. Thirty-five percent had tumour PD-L1 expression TPS < 1% [negative]; 19% were East Asian; and 60% received paclitaxel. Continuation of pembrolizumab may be considered, after corticosteroid taper, if needed (see section 4.2). Date of first authorisation/renewal of the authorisation, Check benefits and financial support you can get, Find out about the Energy Bills Support Scheme, Regulatory approval of COVID-19 vaccine Nuvaxovid, nationalarchives.gov.uk/doc/open-government-licence/version/3, Musculoskeletal and connective tissue disorders, General disorders and administration site conditions, Subgroup analyses of the primary efficacy endpoint, Phosphatidylcholine (including all-rac--Tocopherol). It explains how this product was assessed and its authorisation recommended, as well as its conditions of use. If refrigerated, the vials and/or intravenous bags must be allowed to come to room temperature prior to use. Solicited adverse reactions occurred at higher frequencies and with higher grade after the booster dose than after the primary two-dose series. Patients received pembrolizumab 200 mg every 3 weeks (n=210; KEYNOTE-087) or 10 mg/kg bw every 2 weeks (n=31; KEYNOTE-013) until unacceptable toxicity or documented disease progression. This vaccine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially sodium-free. The efficacy of pembrolizumab was investigated as adjuvant therapy for RCC in KEYNOTE-564, a multicentre, randomised, double-blind, placebo-controlled study in 994 patients with increased risk of recurrence defined as intermediate-high or high risk, or M1 with no evidence of disease (NED). Patients who received prior therapy for melanoma other than surgery were ineligible. Identification of the Alpha variant was based on S gene target failure by PCR. Secondary efficacy outcome measures were ORR and response duration, as assessed by BICR using RECIST 1.1. Pembrolizumab must be permanently discontinued for any Grade 3 immune-related adverse reaction that recurs and for any Grade 4 immune-related adverse reaction toxicity, except for endocrinopathies that are controlled with replacement hormones (see sections 4.2 and 4.8). The median duration was 1.1 month (range 1 day to 45.2 months). endobj As the MHRA website does not include a summary of changes or any sort of version number for the SPC, we are using the "Date . The study excluded patients with EGFR or ALK genomic tumour aberrations; autoimmune disease that required systemic therapy within 2 years of treatment; a medical condition that required immunosuppression; or who had received more than 30 Gy of thoracic radiation within the prior 26 weeks. At the pre-specified interim analysis of ORR (median follow-up time of 12.8 months), statistically significant superiority was achieved for ORR comparing pembrolizumab plus axitinib with sunitinib p-Value < 0.0001. Hepatitis resolved in 60 patients. The baseline characteristics of these patients were: median age of 63 years (range: 24 to 93), 47% age 65 or older; 50% male; 75% White and 16% Asian; 52% and 48% had an ECOG performance status of 0 or 1, respectively. Adverse reactions were usually mild to moderate in severity with a median duration of less than or equal to 2 days for local events and less than or equal to 1 day for systemic events following vaccination. A single booster dose of Nuvaxovid induced an . Patients treated with pembrolizumab without disease progression could be treated for up to 24 months. There were 20 cases of PCR-confirmed symptomatic mild COVID-19 (Nuvaxovid, n=6 [0.5%]; placebo, n=14 [2.4%]) resulting in a point estimate of efficacy of 79.5% (95% CI: 46.8%, 92.1%). Figure 30: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-590 with PD-L1 expression (CPS 10), Figure 31: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-590 with PD-L1 expression (CPS 10), KEYNOTE-522: Controlled study of neoadjuvant and adjuvant therapy in patients with locally advanced, inflammatory, or early-stage triple-negative breast cancer at high risk of recurrence. There were no notable effects in the male and female reproductive organs in monkeys based on 1-month and 6-month repeat-dose toxicity studies (see section 5.3). This is based on the MHRA assessment report with any commercially or personally confidential information removed. KEYTRUDA has not been studied in patients with severe renal impairment (see sections 4.4 and 5.2). Concomitant administration of Nuvaxovid with other vaccines has not been studied. EIR Vinyl Flooring ZXE2001. The median time to onset of pneumonitis was 3.9 months (range 2 days to 27.2 months). arthritis (joint swelling, polyarthritis and joint effusion), ee. We also use cookies set by other sites to help us deliver content from their services. KEYTRUDA as monotherapy is indicated for the treatment of the following MSI-H or dMMR tumours in adults with: - advanced or recurrent endometrial carcinoma, who have disease progression on or following prior treatment with a platinum-containing therapy in any setting and who are not candidates for curative surgery or radiation; - unresectable or metastatic gastric, small intestine, or biliary cancer, who have disease progression on or following at least one prior therapy. /CropBox [0 0 595 842] There was no evidence of an altered pharmacokinetic or safety profile with anti-pembrolizumab binding or neutralising antibody development. The study population characteristics were: median age of 65 years (range: 29 to 88); 55% age 65 or older; 81% male; 77% White; ECOG performance status of 0 (29%) and 1 (71%); and 8% with treated brain metastases at baseline. KEYNOTE-042: Controlled study of NSCLC patients nave to treatment. Secondary outcome measures were ORR (as assessed by BICR using RECIST v1.1) and duration of response. Table 16: Efficacy results in KEYNOTE-407, * A total of 138 patients (51%) who discontinued study treatment in the placebo plus chemotherapy arm crossed over to receive monotherapy pembrolizumab or received a checkpoint inhibitor as subsequent therapy, Based on method by Miettinen and Nurminen, Adverse reactions observed in clinical studies of pembrolizumab as monotherapy or in combination with chemotherapy or other anti-tumour medicines or reported from post-marketing use of pembrolizumab are listed in Table 2. One patient experienced engraftment syndrome post-transplant. The primary efficacy outcome was OS in the ITT population. Uncommon but serious: (see MHRA alerts below for more information) DKA Fournier's Gangrene Lower limb amputation -encourage regular preventative footcare Please see individual drug monographs in BNF/SPC for a complete side-effect profile -see hyperlink in table overleaf. Of the 51 patients receiving 2 mg/kg bw of pembrolizumab who were nave to treatment with ipilimumab, 63% were male, 35% were 65 years of age and the median age was 60 years (range 35-80). The assessment of efficacy and immunogenicity of Nuvaxovid in adolescent participants 12 through 17years of age occurred in the United States in the ongoing paediatric expansion portion of the Phase 3 multicentre, randomised, observer-blinded, placebo-controlled 2019nCoV-301 study. Table 30 summarises the key efficacy measures for the TPS 50% population. Assessment of tumour status was performed every 9 weeks through the first year, then every 12 weeks thereafter. 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