KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of advanced renal cell carcinoma in adults (see section 5.1). Patients on chemotherapy who experienced independently-verified progression of disease after the first scheduled disease assessment were able to crossover and receive 2 mg/kg bw or 10 mg/kg bw of pembrolizumab every 3 weeks in a double-blind fashion. The primary efficacy outcome was OS in the ITT population. The median follow-up time was 11.4 months (range: 0.3 to 26.9 months). The patient will be provided with the patient alert card with each prescription. Treatment continued until unacceptable toxicity or disease progression as determined by the investigator and confirmed by BICR using RECIST 1.1. The primary efficacy outcome measures were PFS as assessed by IRO using RECIST version 1.1 and OS. Corticosteroids can also be used as premedication, when pembrolizumab is used in combination with chemotherapy, as antiemetic prophylaxis and/or to alleviate chemotherapy-related adverse reactions. search for MHRA Yellow Card in the Google Play or Apple App Store. The Patient Information Leaflet provides information for patients on using the medicine safely. Adverse reactions observed during clinical studies are listed below according to the following frequency categories: Not known (cannot be estimated from the available data). 13 0 obj Patients in the placebo arm were offered pembrolizumab as a single agent at the time of disease progression. Immune-related adverse reactions affecting more than one body system can occur simultaneously. /Metadata 2 0 R 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 were treated with pembrolizumab until disease progression or unacceptable toxicity. Enrolment of adolescents completed in June 2021. Nuvaxovid was assessed in individuals 18 years of age and older. 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). In KEYNOTE-042, a higher number of deaths within 4 months of treatment initiation followed by a long-term survival benefit was observed with pembrolizumab monotherapy compared to chemotherapy (see section 5.1). The Novavax COVID-19 Vaccine, Adjuvanted demonstrated a booster response regardless of the vaccine used for primary vaccination. Bevacizumab 5 mg/kg bw on Day 1 or cetuximab 400 mg/m2 on first infusion, then 250 mg/m2 weekly. Based on patients with a best objective response as confirmed complete or partial response. In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Ninety-eight percent of the patients had M1 disease and 2% had M0 disease. Patients were randomised (2:1) to one of the following treatment arms via intravenous infusion: Pembrolizumab 200 mg on Day 1 every 3 weeks in combination with nab-paclitaxel 100 mg/m2 on Days 1, 8 and 15 every 28 days, or paclitaxel 90 mg/m2 on Days 1, 8, and 15 every 28 days, or gemcitabine 1,000 mg/m2 and carboplatin AUC 2 mg/mL/min on Days 1 and 8 every 21 days. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. 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. MSI or MMR tumour status was determined prospectively using PCR or IHC, respectively. 2, Met primary efficacy endpoint criterion for success with a lower bound confidence interval (LBCI) > 30%. Severe infusion-related reactions, including hypersensitivity and anaphylaxis, have been reported in patients receiving pembrolizumab (see section 4.8). /Type /Page Eighty-five percent of patients had visceral metastases, including 21% with liver metastases. Ninety percent of patients were treatment nave, and 10% received prior adjuvant or neoadjuvant platinum-based chemotherapy. >> Allogeneic HSCT prior to treatment with pembrolizumab. A total of 147 symptomatic mild, moderate, or severe COVID-19 cases among all adult participants, seronegative (to SARS-CoV-2) at baseline, were accrued for the complete analysis (PP-EFF Analysis Set) of the primary efficacy endpoint, with 51 (3.62%) cases for Nuvaxovid versus 96 (7.05%) cases for placebo. In Study 3, an ongoing Phase 2a/b randomizsed, observer-blinded, placebo-controlled study, the safety and immunogenicity of booster dose was evaluated in healthy HIV-negative adult participants 18 to 84years of age and medically stable PLWH 18 to 64years of age who were seronegative to SARS-CoV-2 at baseline. The median duration of treatment for pembrolizumab plus lenvatinib was 17.0 months. H0: difference in % = 0 versus H1: difference in % > 0. endobj The safety of pembrolizumab in combination with axitinib or lenvatinib in advanced RCC, and in combination with lenvatinib in advanced EC has been evaluated in a total of 1,456 patients with advanced RCC or advanced EC receiving 200 mg pembrolizumab every 3 weeks with either axitinib 5 mg twice daily or lenvatinib 20 mg once daily in clinical studies, as appropriate. COVID-19 was defined as first episode of PCR-confirmed mild, moderate, or severe COVID-19 with at least one or more of the predefined symptoms within each severity category. Medical management guidelines for both medicines should be followed (see section 4.2 and refer to the SmPC for axitinib). *, The Kaplan-Meier curve for OS for the TPS 50% population is shown in Figure 22. 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). 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. Patients were randomised (1:1) to one of the following treatment arms via intravenous infusion: Pembrolizumab 200 mg and carboplatin AUC 6 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles, and paclitaxel 200 mg/m2 on Day 1 of each 21-day cycle for 4 cycles or nab-paclitaxel 100 mg/m2 on Days 1, 8 and 15 of each 21-day cycle for 4 cycles, followed by pembrolizumab 200 mg every 3 weeks. Clinically stable patients with initial evidence of disease progression were permitted to remain on treatment until disease progression was confirmed. Dont include personal or financial information like your National Insurance number or credit card details. This means that further evidence on this medicinal product is awaited. 10 0 obj Use of pembrolizumab for treatment of patients with advanced or recurrent MSI-H or dMMR endometrial carcinoma. Patients with 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 were ineligible. 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. Common sites of metastases in patients were lung (69%), lymph node (46%), and bone (26%). Patients were treated with pembrolizumab until unacceptable toxicity or disease progression. Assessment of tumour status was performed every 8 weeks. Table 14: Efficacy results in KEYNOTE-189, Pembrolizumab + Pemetrexed + Platinum Chemotherapy, Placebo + Pemetrexed + Platinum Chemotherapy, * A total of 113 patients (57%) who discontinued study treatment in the placebo plus chemotherapy arm crossed over to receive monotherapy pembrolizumab or received a checkpoint inhibitor as subsequent therapy, Individuals who have received a first dose of Nuvaxovid should receive the second dose of Nuvaxovid to complete the vaccination course. arthritis (joint swelling, polyarthritis and joint effusion), ee. Ninety-six percent of patients had M1 disease and 4% M0 disease. Poisoning is usually minimal below 6.5 mmol per litre but may be severe above 8 mmol per litre. Where we have identified any third party copyright information you will need to obtain permission from the copyright holders concerned. A subgroup analysis was performed as part of the final analysis of KEYNOTE-006 in patients who were BRAF wild type (n=525; 63%), BRAF mutant without prior BRAF treatment (n=163; 20%) and BRAF mutant with prior BRAF treatment (n=139; 17%) as summarised in Table 7. << Among the 5 adolescent participants with advanced melanoma treated on KEYNOTE-051, no patient had a complete or a partial response, and 1 patient had stable disease. The primary efficacy outcome was PFS and the secondary efficacy outcome measure was ORR, both assessed by BICR according to the 2007 revised International Working Group (IWG) criteria. Neutralising antibody responses were compared with those observed in seronegative/PCR-negative adult participants aged 18 through 25 years from the adult main study (Per Protocol Immunogenicity ( PP-IMM) Analysis Set) as shown in Table 3. KEYNOTE-042: Controlled study of NSCLC patients nave to treatment. All but two patients were white. KEYTRUDA as monotherapy is indicated for adults with MSI-H or dMMR colorectal cancer in the following settings: - first-line treatment of metastatic colorectal cancer; - treatment of unresectable or metastatic colorectal cancer after previous fluoropyrimidine-based combination therapy. H0: difference in % = 0 versus H1: difference in % > 0, Hypothyroidism resolved in 200 (21.3%) patients, 16 with sequelae. If not used immediately, chemical and physical in-use stability of KEYTRUDA has been demonstrated for 96 hours at 2C to 8C. At the time of the updated analysis, the DFS hazard ratio (95% CI) was 0.68 (0.52, 0.89) in the subgroup of patients with M0-intermediate-high risk of recurrence, 0.60 (0.33, 1.10) in the subgroup of patients with M0-high risk of recurrence, and 0.28 (0.12, 0.66) in the subgroup of patients with M1 NED. Among 370 patients with urothelial carcinoma who were not eligible for cisplatin-containing chemotherapy baseline characteristics were: median age 74 years (82% age 65 or older); 77% male; and 89% White and 7% Asian. The efficacy of pembrolizumab was investigated in KEYNOTE-204, a randomised, open-label, active-controlled study conducted in 304 patients with relapsed or refractory cHL. 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. Clinically stable patients with initial evidence of disease progression were permitted to remain on treatment until disease progression was confirmed. endobj endobj Ninety-three percent had M1 disease. The primary efficacy outcome measure was PFS based on BICR using RECIST 1.1. All participants were offered the opportunity to continue to be followed in the study. Patients were randomised (1:1) to receive pembrolizumab 200 mg intravenously every 3 weeks or investigator's choice of the following chemotherapy regimens given intravenously every 2 weeks: mFOLFOX6 (oxaliplatin, leucovorin, and FU) or mFOLFOX6 in combination with either bevacizumab or cetuximab: Oxaliplatin 85 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. In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6. No dose adjustment is needed for patients with mild or moderate renal impairment. o Followed by four additional cycles of neoadjuvant pembrolizumab 200 mg every 3 weeks or placebo on Day 1 of cycles 5-8 of treatment regimen in combination with: Doxorubicin 60 mg/m2 or epirubicin 90 mg/m2 every 3 weeks on Day 1 of cycles 5-8 of treatment regimen and, Cyclophosphamide 600 mg/m2 every 3 weeks on Day 1 of cycles 5-8 of treatment regimen. /Type /Metadata Administration of Nuvaxovid in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and fetus. The study excluded patients with endometrial sarcoma, carcinosarcoma, pre-existing Grade 3 fistula, uncontrolled BP (> 150/90 mmHg), significant cardiovascular impairment or event within previous 12 months, or patients who had active autoimmune disease or a medical condition that required immunosuppression. Patients must have undergone lymph node dissection, and if indicated, radiotherapy within 13 weeks prior to starting treatment. Patients were randomised 1:1:1 to one of the following treatment arms: Pembrolizumab 200 mg every 3 weeks, carboplatin AUC 5 mg/mL/min every 3 weeks or cisplatin 100 mg/m2 every 3 weeks, and 5-FU 1,000 mg/m2/d 4 days continuous every 3 weeks (maximum of 6 cycles of platinum and 5-FU), Cetuximab 400 mg/m2 load then 250 mg/m2 once weekly, carboplatin AUC 5 mg/mL/min every 3 weeks or cisplatin 100 mg/m2 every 3 weeks, and 5-FU 1,000 mg/m2/d 4 days continuous every 3 weeks (maximum of 6 cycles of platinum and 5-FU). Based on the severity of the adverse reaction, pembrolizumab should be withheld and corticosteroids administered. ?F} 7N{)"W}^ufImeYXgK'j m*nd801F 4sC@.b#-="pwkb9Ei!W-\:#5gMFyJbPd`(& Dma;}@zqZ+/RwHrGr&iy3gMdyuDT@S0:n@BsRssHsVBT{{V!B Thirty-five percent had tumour PD-L1 expression TPS < 1% [negative]; 19% were East Asian; and 60% received paclitaxel. The baseline characteristics of these 383 patients were: median age of 63 years (range: 28 to 89), 41% age 65 or older; 82% male; 34% White and 56% Asian; 43% and 57% had an ECOG performance status of 0 and 1, respectively. To help us improve GOV.UK, wed like to know more about your visit today. Cisplatin could be administered on Day 2 of each 3-week treatment cycle. 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), KEYNOTE-006: Controlled study in melanoma patients nave to treatment with ipilimumab. Product must not be mixed with other medicinal products except those mentioned in section 6.6 Met primary endpoint... 4 % M0 disease be provided with the patient will be provided with the patient information provides! 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