ATEZOLIZUMAB (TECENTRIQ ) in urothelial carcinoma

Transcription

1 DRUG ADMINISTRATION SCHEDULE Day Drug Daily Dose Route Diluent Rate Day 1 Atezolizumab 1200 mg IV Infusion 250mL 0.9% Sodium Chloride Over 60 minutes* *The initial dose of atezolizumab must be administered over 60 minutes. If the first infusion is well tolerated, all subsequent infusions may be administered over 30 minutes. CYCLE LENGTH AND NUMBER OF DAYS Administered every 21 days (3 weeks) until disease progression or unacceptable toxicity. APROVED INDICATIONS NICE TA492 Atezolizumab is recommended for use within the Cancer Drugs Fund as an option for untreated locally advanced or metastatic urothelial carcinoma in adults, for whom cisplatinbased chemotherapy is unsuitable, only if the conditions of the managed access agreement for atezolizumab are followed. See National CDF list for full prescribing restrictions. Available at EXCLUSION CRITERIA Hypersensitivity to the active substance or any of the excipients e.g. L-histidine, polysorbate 20. patients with hepatitis B or hepatitis C infection active systemic autoimmune disease interstitial lung disease prior pneumonitis requiring systemic corticosteroid therapy a history of severe hypersensitivity to another monoclonal antibody. PREMEDICATION None routinely recommended. The rate of infusion should be reduced, or treatment should be interrupted in patients with Grade 1 or 2 infusion related reactions. Atezolizumab should be permanently discontinued in patients with Grade 3 or 4 infusion related reactions. Patients with Grade 1 or 2 infusionrelated reactions may continue to receive atezolizumab with close monitoring; premedication with antipyretic and antihistamines may be considered. RECOMMENDED TAKE HOME MEDICATION Loperamide 4mg after first loose stool then 2mg after each loose stool thereafter up to a maximum of 16mg in 24 hours. I atezolizumab urothelial crp17u019v1.0 Page 1 of 6

2 NVESTIGATIONS / MONITORING REQUIRED Pre-treatment: Assessment of renal function, FBC, Cardiac history, FBC, U&Es, glucose, LFTs and tumour markers as appropriate. Prior to each cycle: FBC, U&Es, glucose, and LFTs. ASSESSMENT OF RESPONSE Metastatic: Tumour size and patient symptomatic response. REVIEW BY CLINICIAN To be reviewed either by a Nurse, Pharmacist or Clinician before every cycle. NURSE / PHARMACIST LED REVIEW Each cycle as applicable according to local protocols. ADMINISTRATION NOTES CAUTION Atezolizumab administration can result in severe and fatal immune-mediated adverse reactions (iraes). iraes may involve gastrointestinal, endocrine, skin, liver, nervous, lung and other organ systems. Unless an alternate aetiology has been identified, signs and symptoms suggestive of iraes must be considered inflammatory and Immunotherapy related. Early diagnosis and appropriate management are essential to minimise life threatening complications. Systemic high dose corticosteroid with or without additional immunosuppressive therapy may be required for management of severe iraes Administer using a low-protein binding 0.2-5micron in-line or add-on filter. Consider premedication with antipyretic and antihistamine in patients with mild or moderate infusion reactions (close monitoring required.) 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. However, systemic corticosteroids or other immunosuppressants can be used after starting pembrolizumab to treat immune related adverse reactions. All patients must be provided with the Patient Alert Card with each prescription as per the marketing authorisation. EXTRAVASATION See NCA/Local Policy TOXICITIES (Non-immune related see Dose Modification section for immune-related toxicities) Diarrhoea Nausea & vomiting Fatigue Arthralgia Rash Anaemia Pruritus atezolizumab urothelial crp17u019v1.0 Page 2 of 6

3 DOSE MODIFICATION / TREATMENT DELAYS Dose reductions of atezolizumab are not recommended. Haematological Toxicity Neutrophils (x 10 9 /L) Platelets (x 10 9 /L) Dose 1.5 And % dose Non-Haematological Toxicity Immune Related Reactions Pneumonitis Grade 2 Grade 3 or 4 Treatment may be resumed when the event improves to Grade 0 or Grade 1 within 12 weeks, and corticosteroids have been reduced to 10 mg prednisone or equivalent per day Hepatitis Grade 2: (ALT or AST > 3 to 5 x upper limit of normal (ULN) or blood bilirubin > 1.5 to 3 x ULN) Grade 3 or 4: (ALT or AST > 5 x ULN Or blood bilirubin > 3 x ULN) Treatment may be resumed when the event improves to Grade 0 or Grade 1 within 12 weeks and corticosteroids have been reduced to 10 mg prednisone or equivalent per day Colitis Grade 2 or 3 Diarrhoea (increase of 4 stools/day over baseline) Or Symptomatic Colitis Grade 4 Diarrhoea or Colitis (life threatening; urgent intervention indicated) Treatment may be resumed when the event improves to Grade 0 or Grade 1 within 12 weeks and corticosteroids have been reduced to 10 mg prednisone equivalent per day Hypothyroidism or hyperthyroidism Symptomatic Adrenal insufficiency Symptomatic Hypothyroidism: Treatment may be resumed when symptoms are controlled by thyroid replacement therapy and TSH levels are decreasing Hyperthyroidism: Treatment may be resumed when symptoms are controlled by antithyroid medicinal product and thyroid function is improving Treatment may be resumed when the symptoms improve to Grade 0 or Grade 1 within 12 weeks and corticosteroids have been reduced to 10 mg prednisone or equivalent per day and patient is stable on replacement therapy atezolizumab urothelial crp17u019v1.0 Page 3 of 6

4 Hypophysitis Grade 2 or 3 Grade 4 Treatment may be resumed when the symptoms improve to Grade 0 or Grade 1 within 12 weeks and corticosteroids have been reduced to 10 mg prednisone or equivalent per day and patient is stable on replacement therapy Type 1 diabetes mellitus Grade 3 or 4 hyperglycaemia (fasting glucose > 250 mg/dl or 13.9 mmol/l) Treatment may be resumed when metabolic control is achieved on insulin replacement therapy Infusion-related reactions Grade 1 or 2 Grade 3 or 4 Reduce infusion rate or interrupt. Treatment may be resumed when the event is resolved Rash Grade 3 Grade 4 Treatment may be resumed when rash is resolved and corticosteroids have been reduced to 10 mg prednisone or equivalent per day Myasthenic syndrome/myasthenia gravis, Guillain-Barré syndrome and Meningoencephalitis All Grades Pancreatitis Grade 3 or 4 serum amylase or lipase levels Treatment may be resumed when serum amylase and lipase levels increased (> 2 x ULN) or improve to Grade 0 or Grade 1 within 12 weeks, or symptoms of Grade 2 or 3 pancreatitis pancreatitis have resolved, and corticosteroids have been reduced to 10 mg prednisone or equivalent per day Grade 4 or any grade of recurrent pancreatitis Renal Impairment No adjustment of the starting dose is needed in patients with mild or moderate renal impairment, but not recommended in patients with severe renal impairment or end stage renal disease. Hepatic Impairment No adjustment of the starting dose is needed in patients with mild hepatic impairment, but not recommended in patients with moderate or severe hepatic impairment (bilirubin >1.5 x ULN, ALT >3 x ULN). atezolizumab urothelial crp17u019v1.0 Page 4 of 6

5 MANAGEMENT OF TOXICITY FLOW DIAGRAM (ADAPTED FROM NCCC POLICY DATED AUG 2015) Patient on ipilimumab, nivolumab, pembrolizumab or atezolizumab In hours contact local acute oncology service or oncology day unit* Out of hours contact on-call oncology nurse or on-call oncology consultant* Note May need to arrange admission of patient or transfer (if already admitted) in patient oncology/acute oncology bed. (local arrangements may vary) Mild-moderate Toxicity Persistent Moderate or Severe/Life Threatening Toxicity Investigations and supportive measures Consider Prednisolone 1mg/kg/day (Consult on-call oncologist*) Investigations and supportive measures IV Methylprednisolone 2mg/kg/day (Consult on-call oncologist *) May need alternative immunosuppressive drugs *Check local Trust arrangements for whom to contract atezolizumab urothelial crp17u019v1.0 Page 5 of 6

6 TREATMENT LOCATION Cancer Centre and Cancer Units* Cancer units must have arrangements for monitoring and management of immune related toxicities and access to advices from oncologist experienced in use of immunotherapies. REFERENCES 1. Summary of Product Characteristics: Atezolizumab (Tecentriq ) Updated 16/11/17 2. NICE, SPC TA492 Atezolizumab for untreated locally advanced or metastatic urothelial cancer when cisplatin is unsuitable, 06 December 2017 Document Control Document Title: ATEZOLIZUMAB (TECENTRIQ ) Document No: Reviewer: Approved by: Summary of Changes CRP17 U019 Chris Beck Chemotherapy Pharmacist Northern Cancer Alliance Steve Williamson Consultant Pharmacist Northern Cancer Alliance V1.0 First draft Current Version: 1.0 Date Approved: Due for Review atezolizumab urothelial crp17u019v1.0 Page 6 of 6