Systemic Anti Cancer Treatment Protocol Atezolizumab Non-small cell lung cancer PROTOCOL REF: MPHAATNSCLC (Version No: 1.0) Approved for use in: Locally advanced/metastatic non squamous or squamous non-small cell lung cancer (stage IIIB or IV) where the following criteria is met: PD-L1 negative or PD-L1 unquantifiable at PD-L1 assay or PD-L1 status cannot be determined on account of insufficient lung cancer tissue being available for PD1 assay. Patient has either progressed after previously receiving at least 2 cycles of platinum containing chemotherapy for stage IIIB or IV non-small cell lung cancer and also a targeted treatment if the tumour is EGFR +ve or ALK +ve or progressed within 6 months of completing platinum-based chemotherapy given as an adjuvant or neoadjuvant therapy or concurrent with radiotherapy Performance status of 0 or 1 and would otherwise be potentially fit for docetaxel based 2 nd line chemotherapy The patient has no symptomatically active brain metastases or leptomeningeal metastases. The patient has not received prior treatment with an anti-pd-1, anti-pd-l1, anti- PDL2, anti-cd137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA- 4) antibody Blueteq registration required Review: May 2021 Page 1 of 8 Protocol reference: MPHAATNSCLC
A formal medical review as to whether treatment with atezolizumab should continue or not will be scheduled to occur at least by the end of the first 9 weeks of treatment Treatment breaks of up to 12 weeks beyond the expected cycle length of atezolizumab are allowed solely to allow immune toxicities to settle Dosage: Drug Dosage Route Frequency Atezolizumab 1200mg (flat dose) IV infusion 3 weekly Atezolizumab will be stopped at 2 years of treatment or on loss of clinical benefit or unacceptable toxicity, whichever occurs first. Supportive treatments: Domperidone 10mg oral tablets 3 times a day or as required Extravasation risk: Monoclonal antibody treat symptomatically, no specific recommendations. Refer to the network guidance for the prevention and management of extravasation Interactions: No formal pharmacokinetic drug interaction studies have been conducted with atezolizumab. Since atezolizumab is cleared from the circulation through catabolism, no metabolic drug-drug interactions are expected. The use of systemic corticosteroids or immunosuppressants before starting atezolizumab should be avoided because of their potential interference with the pharmacodynamic activity and efficacy of atezolizumab. However, systemic corticosteroids or other immunosuppressants can be used to treat immune-related adverse reactions after starting atezolizumab. Further guidance can be found in the toxicity table below. Review: May 2021 Page 2 of 8 Protocol reference: MPHAATNSCLC
Please consult summary of product characteristics via https://www.medicines.org.uk/emc for full list of interactions. Administration: Day Drug Dose Route Diluent and rate 1 Atezolizumab 1200mg IV infusion 250mL sodium chloride 0.9%. Infused over 60 minutes for cycle 1 if well tolerated cycle 2 onwards can be administered over 30minutes in a nonpyrogenic line with a 0.2 micron filter Routine prophylaxis against infusion related reactions is not required. However the patient should be monitored during the infusion, and treatment given if necessary (antihistamines, steroids etc). Review: May 2021 Page 3 of 8 Protocol reference: MPHAATNSCLC
Main Toxicities: Systemic high-dose corticosteroid with or without additional immunosuppressive therapy may be required for management of severe immune-related adverse reactions. Refer to trust immunotherapy toxicity management guidelines for further advice. Immune related adverse reaction Severity Treatment modification Pneumonitis Grade 2 Treatment may be resumed when the event improves to Grade 0 or Grade 1 within 12 weeks, and Grade 3 or 4 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) 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 Treatment may be resumed when the event improves to Grade 0 or Grade 1 within 12 weeks and prednisone equivalent per day Review: May 2021 Page 4 of 8 Protocol reference: MPHAATNSCLC
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 anti-thyroid 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 and patient is stable on replacement therapy Hypophysitis Grade 2 or 3 Treatment may be resumed when the symptoms improve to Grade 0 or Grade 1 within 12 weeks and and patient is stable on replacement therapy Type 1 diabetes mellitus Infusion-related reactions Grade 4 Grade 3 or 4 hyperglycaemia (fasting glucose > 250 mg/dl or 13.9 mmol/l) Grade 1 or 2 Grade 3 or 4 Treatment may be resumed when metabolic control is achieved on insulin replacement therapy Reduce infusion rate or interrupt. Treatment may be resumed when the event is resolved Rash Grade 3 Treatment may be resumed when rash is resolved and Review: May 2021 Page 5 of 8 Protocol reference: MPHAATNSCLC
Grade 4 Myasthenic All Grades syndrome/myasthenia gravis, Guillain-Barré syndrome and Meningoencephalitis Pancreatitis Grade 3 or 4 serum amylase or lipase levels increased (> 2 x ULN) or Grade 2 or 3 pancreatitis Grade 4 or any grade of recurrent pancreatitis Treatment may be resumed when serum amylase and lipase levels improve to Grade 0 or Grade 1 within 12 weeks, or symptoms of pancreatitis have resolved, and Myocarditis Grade 2 Treatment may be resumed when the symptoms improve to Grade 0 or Grade 1 within 12 weeks and Other immune-related adverse reactions Grade 3 and 4 Grade 2 or Grade 3 Withhold until adverse reactions recovers to Grade 0-1 within 12 weeks, and corticosteroids have been reduced to 10 mg. Grade 4 or recurrent Grade 3 (except endocrinopathies controlled with replacement hormones) Review: May 2021 Page 6 of 8 Protocol reference: MPHAATNSCLC
Investigations and treatment plan: Pre C1 C2 C3 Pre cycle 4 Oncology Team Assessment X X Informed Consent X C4 C5 Pregnancy test if applicable. Women of childbearing potential have to use effective contraception during and for 5 months after treatment with atezolizumab. Serum samples for HIV, Hep C antibody and HBsAg if risk factors Ongoing Every 12 weeks thereafter or as clinically indicated Nursing Assessment Including toxicity assessment X X X X X Every cycle FBC, U&E, LFTs and LDH Local hospital/gp surgery 48 hours before due dose TFTs and cortisol Local hospital/gp surgery 48 hours before due dose X X X X X Every cycle X X X X X X Every cycle Blood glucose X X X X X X Every cycle Lipid profile (cholesterol) X X X Every 6 weeks CT scan X X Every 12 weeks thereafter or as clinically indicated Blood pressure X X X X X X Every cycle ECOG PS X X X X X X Every cycle Weight recorded X X X X X X Every cycle Review: May 2021 Page 7 of 8 Protocol reference: MPHAATNSCLC
Dose Modifications and Toxicity Management: No dose reductions of atezolizumab are recommended toxicity should be managed with a dose delay or discontinuation of treatment. Systemic high-dose corticosteroid with or without additional immunosuppressive therapy may be required for management of severe immune-related adverse reactions. Refer to trust immunotherapy toxicity management guidelines for further advice. Hepatic impairment Based on a population pharmacokinetic analysis, no dose adjustment is required for patients with mild hepatic impairment. Atezolizumab has not been studied in patients with moderate or severe hepatic impairment Renal impairment Based on a population pharmacokinetic analysis, no dose adjustment is required in patients with mild or moderate renal impairment. Data from patients with severe renal impairment are too limited to draw conclusions on this population. Patient Counselling Points Contact the triage team for the following: New or worsening cough, chest pain or shortness of breath Diarrhoea or severe abdominal pain Jaundice, severe nausea or vomiting, or easy bruising or bleeding Persistent or unusual headache, extreme weakness, dizziness or fainting, or vision changes Monitor for signs of infection / sepsis Flu like symptoms are common, particularly during cycle 1. References: https://www.medicines.org.uk/emc BNF available via: https://bnf.nice.org.uk/ Review: May 2021 Page 8 of 8 Protocol reference: MPHAATNSCLC