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. It explains how to use and prescribe a medicine. Adrenal insufficiency (primary and secondary) has been reported in patients receiving pembrolizumab. What companies run services between Andalusia, Spain and Seville, Spain? In subgroup analyses, a reduced survival benefit of pembrolizumab compared to docetaxel was observed for patients who were never-smokers or patients with tumours harbouring EGFR activating mutations who received at least platinum-based chemotherapy and a tyrosine kinase inhibitor; however, due to the small numbers of patients, no definitive conclusions can be drawn from these data. The efficacy and safety of pembrolizumab in patients with tumours that do not express PD-L1 have not been established. Adrenal insufficiency resolved in 17 patients, 11 with sequelae. Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. The prescriber must discuss the risks of KEYTRUDA therapy with the patient. Table 21: Response to pembrolizumab 200 mg every 3 weeks in patients with urothelial carcinoma previously treated with chemotherapy in KEYNOTE-045, Number (%#) of patients with duration 6 months, Number (%#) of patients with duration 12 months, Manufacturing and Import authorisations. Treatment could continue beyond progression if the patient was clinically stable and was considered to be deriving clinical benefit by the investigator. Preparation and administration of the infusion. . << Patients received pembrolizumab 200 mg every 3 weeks until unacceptable toxicity or disease progression. Table 15: Efficacy results by PD-L1 expression in KEYNOTE-189 % The patient may also choose to report any adverse drug reaction 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). Patients should be monitored for changes in renal function, and other causes of renal dysfunction excluded. Well send you a link to a feedback form. Pharmacotherapeutic group: Vaccine, other viral vaccines, ATC code: J07BX03. nephritis (autoimmune nephritis, tubulointerstitial nephritis and renal failure, renal failure acute, or acute kidney injury with evidence of nephritis, nephrotic syndrome, glomerulonephritis and glomerulonephritis membranous), gg. Concomitant administration of Nuvaxovid with other vaccines has not been studied. The efficacy of pembrolizumab was investigated in KEYNOTE-177, a multicentre, randomised, open-label, active-controlled study that enrolled patients with previously untreated metastatic MSI-H or dMMR CRC. KEYTRUDA is for intravenous use. Data were available for 95 of the 106 endpoint cases (90%). Efficacy results by MMR subgroups were consistent with overall study results. Patients without disease progression could be treated for up to 24 months. Tourist area. 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. Administration of pembrolizumab was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered to be deriving clinical benefit by the investigator. EFS was defined as the time from randomisation to the first occurrence of any of the following events: progression of disease that precludes definitive surgery, local or distant recurrence, second primary malignancy, or death due to any cause. In patients treated with pembrolizumab in combination with axitinib or lenvatinib, the proportion of patients who experienced a shift from baseline to a Grade 3 or 4 laboratory abnormality was as follows: 23.0% for lipase increased (not measured in patients treated with pembrolizumab and axitinib), 12.0% for lymphocyte decreased, 11.4% for sodium decreased, 11.2% for amylase increased, 11.2% for triglycerides increased, 10.4% for ALT increased, 8.9% for AST increased, 7.8% for glucose increased, 6.8% for phosphate decreased, 6.1% for potassium decreased, 5.1% for potassium increased, 4.5% for cholesterol increased, 4.4% for creatinine increased, 4.2% for haemoglobin decreased, 4.0% for magnesium decreased, 3.5% for neutrophils decreased, 3.1% for alkaline phosphatase increased, 3.0% for platelets decreased, 2.8% for bilirubin increased, 2.2% for calcium decreased, 1.7% for white blood cells decreased, 1.6% for magnesium increased, 1.5% for prothrombin INR increased, 1.4% for glucose decreased, 1.2% for albumin decreased, 1.2% for calcium increased, 0.4% for sodium increased, and 0.1% for haemoglobin increased. Long-term hormone replacement therapy may be necessary in cases of immune-related endocrinopathies. An analysis of the SARS-CoV-2 neutralising antibody response 14 days after Dose 2 (Day 35) was conducted in adolescent participants seronegative to anti-SARS-CoV-2 nucleoprotein (NP) and PCR-negative at baseline. << Among patients with BRAF mutant tumours, 139 (46%) were previously treated with a BRAF inhibitor. Sixteen percent (16%) had disease progression following platinum-containing neoadjuvant or adjuvant chemotherapy, and 84% had received 1-2 prior systemic regimens for metastatic disease. Mild COVID-19 was defined as fever, new onset cough or at least 2 or more additional COVD-19 symptoms. The use of systemic corticosteroids or immunosuppressants before starting pembrolizumab should be avoided because of their potential interference with the pharmacodynamic activity and efficacy of pembrolizumab. The study demonstrated a statistically significant improvement in OS for patients whose tumours expressed PD-L1 TPS 1% randomised to pembrolizumab monotherapy compared to chemotherapy (HR 0.82; 95% CI 0.71, 0.93 at the final analysis) and in patients whose tumours expressed PD-L1 TPS 50% randomised to pembrolizumab monotherapy compared to chemotherapy. This information is for use by healthcare professionals. Twenty-one percent had received 2 prior systemic regimens in the metastatic setting. Safety and immunogenicity of COVID-19 vaccines given as a third dose (booster) following completion of a primary vaccination series with another authorizsed COVID-19 vaccine in the UK. The safety and efficacy of pembrolizumab were investigated in KEYNOTE-052, a multicentre, open-label study for the treatment of locally advanced or metastatic urothelial carcinoma in patients who were not eligible for cisplatin-containing chemotherapy. In urothelial carcinoma, a higher number of deaths within 2 months was observed in pembrolizumab compared to chemotherapy (see section 5.1). It explains how to use and prescribe a medicine. If specified in the indication, patient selection for treatment with KEYTRUDA based on the tumour expression of PD-L1 should be confirmed by a validated test (see sections 4.1, 4.4, 4.8, and 5.1). /Resources 20 0 R Pneumonitis led to discontinuation of pembrolizumab in 131 (1.7%) patients. Approval date: September 2019, updated December 2019 Review date: December 2021 (or earlier if indicated) South East London Area Prescribing Committee. Eighty-one percent were refractory to at least one prior therapy, including 34% who were refractory to first line therapy. To discuss the benefits and possible side-effects of treatment with the patient. Randomisation was stratified by tumour PD-L1 expression (TPS < 1% [negative] vs. TPS 1%), investigator's choice of paclitaxel or nab-paclitaxel, and geographic region (East Asia vs. non-East Asia). /Type /Page Disease characteristics were squamous (21%) and non-squamous (70%); stage IIIA (2%); stage IIIB (7%); stage IV (91%); stable brain metastases (15%) and the incidence of mutations was EGFR (8%) or ALK (1%). The study demonstrated statistically significant improvements in OS and ORR for patients randomised to pembrolizumab as compared to chemotherapy. Table 12 summarises key efficacy measures for the entire intent to treat (ITT) population. Of 14 patients in KEYNOTE-204 who proceeded to allogeneic HSCT after treatment with pembrolizumab, 8 patients reported acute GVHD and 3 patients reported chronic GVHD, none of which were fatal. In these patient populations, the most frequent adverse reactions were diarrhoea (58%), hypertension (54%), hypothyroidism (46%), fatigue (41%), decreased appetite (40%), nausea (40%), arthralgia (30%), vomiting (28%), weight decreased (28%), dysphonia (28%), abdominal pain (28%), proteinuria (27%), palmar-plantar erythrodysaesthesia syndrome (26%), rash (26%), stomatitis (25%), constipation (25%), musculoskeletal pain (23%), headache (23%) and cough (21%). Alternatively, ALSA operates a bus from Malaga to Seville 4 times a day. FOLFIRI (irinotecan, leucovorin, and FU) or FOLFIRI in combination with either bevacizumab or cetuximab: Irinotecan 180 mg/m2, leucovorin 400 mg/m2 (or levoleucovorin 200 mg/m2), and FU 400 mg/m2 bolus on Day 1, then FU 2,400 mg/m2 over 46-48 hours. Table 9 summarises efficacy results by PD-L1 expression. A 30% reduction in antibody responses to Nuvaxovid was noted as assessed by an anti-spike IgG assay with seroconversion rates similar to participants who did not receive concomitant influenza vaccine (see section 4.5 and section 4.8). Hepatitis resolved in 60 patients. %PDF-1.4 Table 17: Efficacy results by PD-L1 expression in KEYNOTE-407 KEYTRUDA should be withheld or discontinued to manage adverse reactions as described in Table 1. The primary efficacy outcome measures were OS and PFS (as assessed by BICR using RECIST 1.1). In KEYNOTE-177, the hazard rates for overall survival events were greater for pembrolizumab compared with chemotherapy for the first 4 months of treatment, followed by a long-term survival benefit for pembrolizumab (see section 5.1). Data about efficacy of pembrolizumab in combination with platinum chemotherapy are limited in this patient population. In the event of an overdose, monitoring of vital functions and possible symptomatic treatment is recommended. Table 43: Efficacy results in KEYNOTE-826 for patients with PD-L1 expression (CPS 1), Pembrolizumab 200 mg every 3 weeks plus Chemotherapy* with or without bevacizumab, Placebo plus Chemotherapy* with or without bevacizumab, * Chemotherapy (paclitaxel and cisplatin or paclitaxel and carboplatin), $>H}X@z%|!T|W=^ewx LcX/)PeIe61Knwszc`A[Av}pS*]?u5-QVe hU!y?4-03,1u#cWZS$Sm,^k]z?(w9/nWg9. 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. No dose reductions are recommended for KEYTRUDA. Table 32 summarises the efficacy measures by IMDC risk category based on the final OS analysis at a median follow-up of 37.7 months. referring specialist and the MHRA yellow card scheme 1. Dont include personal or financial information like your National Insurance number or credit card details. Animal reproduction studies have not been conducted with pembrolizumab; however, in murine models of pregnancy blockade of PD-L1 signalling has been shown to disrupt tolerance to the foetus and to result in an increased foetal loss (see section 5.3). If you are concerned about an adverse event, it should be reported on a Yellow card. The incidences of immune-related adverse reactions were 36.1% all Grades and 8.9% for Grades 3-5 for pembrolizumab monotherapy in the adjuvant setting (n=1,480) and 24.2% all Grades and 6.4% for Grades 3-5 in the metastatic setting (n=5,375). No dose adjustment is needed for patients with mild or moderate hepatic impairment. It is used by healthcare professionals, such as doctors, nurses and pharmacists. Patients with active, non-infectious pneumonitis, an allogeneic HSCT within the past 5 years (or > 5 years but with symptoms of GVHD), active autoimmune disease, a medical condition that required immunosuppression, or an active infection requiring systemic therapy were ineligible for the study. Patients who tolerated axitinib 5 mg twice daily for 2 consecutive treatment cycles (i.e. ECOG performance status 3) considered not eligible for chemotherapy. Assessment of tumour status was performed at baseline and then every 8 weeks. All 827 of these patients received prior systemic therapy for EC: 69% had one, 28% had two, and 3% had three or more prior systemic therapies. As with all vaccines, vaccination with Nuvaxovid may not protect all vaccine recipients. Please refer to the UK approved SPC and PIL supplied electronically with the German As with other intramuscular injections, the vaccine should be given with caution in individuals receiving anticoagulant therapy or those with thrombocytopenia or any coagulation disorder (such as haemophilia) because bleeding or bruising may occur following an intramuscular administration in these individuals. KEYTRUDA as monotherapy is indicated for the first-line treatment of metastatic non-small 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. Twelve percent of patients had BRAF mutations and 36% had RAS mutations; 39% and 34% were undetermined for BRAF and RAS mutations, respectively. o Following surgery, 9 cycles of adjuvant pembrolizumab 200 mg every 3 weeks or placebo were administered. Pembrolizumab in combination with chemotherapy (see section 4.2). Patients were enrolled regardless of PD-L1 tumour expression status. /Length 29 0 R Allogeneic HSCT prior to treatment with pembrolizumab. Secondary efficacy outcome measures were ORR and duration of response, according to RECIST v1.1, as assessed by investigator. Nodular-sclerosis was the more represented cHL histological subtype (~ 81%) and bulky disease, B symptoms and bone marrow involvement were present in approximately 21%, 28% and 4% of patients, respectively. Steady-state concentrations of pembrolizumab were reached by 16 weeks of repeated dosing with an every 3 week regimen and the systemic accumulation was 2.1-fold. EVUSHELD is indicated for the treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk of progressing to severe COVID-19 (see sections 4.2, 5.1 and 5.2).. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 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