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NECN CHEMOTHERAPY HANDBOOK PROTOCOL
Cumbria, Northumberland, Tyne & WearArea Team
Nivolumab (Opdivo®) for treatment of advanced melanoma and Renal Cell Cancer
(Also advanced/ metastatic NSCLC EMAS patients only -Nov 2016)
DRUG ADMINISTRATION SCHEDULE (SINGLE AGENT
Day
Drug
Daily dose
Route
Diluent
Rate
1
Nivolumab*
3mg/kg
IV infusion
Sodium chloride
0.9% 100mL
60 minutes
Cycle Length and Number of Days
Every 14 days until disease progression or unacceptable toxicity.
DRUG ADMINISTRATION SCHEDULE (COMBINATION)
When given in combination with iplilumimab for malignant melanoma an alternative lower dose
schedule (1mg/kg) is used for first 4 cycles of a 21 day cycle.
Day
Drug
Daily dose
Route
1
Nivolumab*
1mg/kg
IV infusion
1
Iplilumimab
3 mg/kg
IV Infusion
Diluent
100mL Sodium
chloride 0.9%
100 ml Sodium
chloride 0.9%
Rate
60 minutes
90 minutes
Cycle Length and Number of Days
Every 21 days for 4 cycles then stop iplilumimab and continue on 2 weekly nivolumab at
3mg/kg as above
Nivolumab is supplied as 40mg or 100mg single-use vials, each containing 10mL or 40mL,
respectively. It must be prepared in pharmacy aseptic units and treated with the same
precautions as cytotoxic medicines.
APPROVED INDICATIONS
Nivolumab for monotherapy or in combination with iplilumimab is indicated for the treatment
of advanced (unresectable or metastatic) melanoma in adults.
Nivolumab for second and subsequent line treatment of renal cell cancer is available on
Cancer Drug Fund following Draft NICE approval on 21.10.16. (Note funding will transfer
from CDF to baseline commissioning 30 days after final NICE TA issued)
Nivolumab for second line treatment of non-small cell lung cancer is only available under the
EAMS scheme for patients in 2016.
nivolumab for melanoma and rcc s16 004
Issue Date: 31 October 2014
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Expiry Date: 31 October 2016
NECN CHEMOTHERAPY HANDBOOK PROTOCOL
Cumbria, Northumberland, Tyne & WearArea Team
PREMEDICATION
Not routinely required.
RECOMMENDED TAKE HOME MEDICATION
Metoclopramide 10mg TDS as required.
INVESTIGATIONS / MONITORING REQUIRED
PD-L1 test (non-squamous NSCLC only).
FBC, U&E, LFT, including glucose and bicarbonate at baseline and before each dose.
ASSESSMENT OF RESPONSE
Metastatic: Tumour size and patient symptomatic response.
REVIEW BY CLINICIAN
To be reviewed by either a Nurse, Pharmacist or Clinician before every cycle.
NURSE / PHARMACIST LED REVIEW
On cycles where not seen by clinician.
ADMINISTRATION NOTES
CAUTION
Nivolumab 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

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
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Patients should be monitored continuously (at least up to 5 months after the last dose)
mas an adverse reaction with Nivolumab may occur at any time during or after
discontinuation of Nivolumab therapy.
Nivolumab should not be resumed while the patient is receiving immunosuppressive
doses of corticosteroids or other immunosuppressive therapy. Prophylactic antibiotics
should be used to prevent opportunistic infections in patients receiving
immunosuppressive therapy.
Nivolumab must be permanently discontinued for any severe immune-related adverse
reaction that recurs and for any life-threatening immune-related adverse reaction.
Use an infusion set and an in-line, sterile, non-pyrogenic, low protein binding filter (pore
size of 0.2 µm to 1.2 µm)
Patients should be given an alert card and be told to report any side effects
EXTRAVASATION See NECN/Local Policy
nivolumab for melanoma and rcc s16 004
Issue Date: 31 October 2014
Page 2 of 5
Expiry Date: 31 October 2016
NECN CHEMOTHERAPY HANDBOOK PROTOCOL
Cumbria, Northumberland, Tyne & WearArea Team
TOXICITIES (None Immune related)
Fatigue
Pruritis and rash
Diarrhoea
Nausea
Muscle pain
Respiratory tract infections
LFT derangement
Reduced appetite
Peripheral neuropathy
DOSE MODIFICATION / TREATMENT DELAYS
Immune-related
adverse reaction
Immune-related
pneumonitis
Severity
Treatment modification
Grade 2
Withhold nivolumab until symptoms resolve,
radiographic abnormalities improve, and
management with corticosteroids is complete.
Initiate corticosteroids at a dose of 1mg/kg/day
methylprednisolone IV or oral equivalent. May
resume nivolumab after corticosteroid taper.
If there is no improvement, increase dose to 2 to
4mg/kg/day methylprednisolone IV or oral
equivalent and permanently discontinue nivolumab
Grade 3 or 4
Immune-related
colitis
Grade 2 or 3
Permanently discontinue nivolumab. Initiate
corticosteroids at a dose of 2 to 4mg/kg/day
methylprednisolone IV or oral equivalent
Withhold nivolumab until symptoms resolve.
Grade 2 – if persistent, manage with
corticosteroids at a dose of 0.5 to 1mg/kg/day
methylprednisolone IV or oral equivalent. Upon
improvement, taper corticosteroid and resume
nivolumab. If worsening or no improvement,
increase corticosteroid dose to 1 to 2 mg/kg/day
methylprednisolone IV or oral equivalent and
permanently discontinue Nivolumab.
Grade 3 – Initiate corticosteroids at a dose of 1 to 2
mg/kg/day methylprednisolone IV or oral
equivalent. Upon improvement, taper corticosteroid
and resume nivolumab. If worsening or no
improvement, permanently discontinue nivolumab.
Grade 4
nivolumab for melanoma and rcc s16 004
Issue Date: 31 October 2014
Permanently discontinue Nivolumab. Initiate
corticosteroids at a dose of 1 to 2 mg/kg/day
methylprednisolone IV or oral equivalent.
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Expiry Date: 31 October 2016
NECN CHEMOTHERAPY HANDBOOK PROTOCOL
Cumbria, Northumberland, Tyne & WearArea Team
Immune-related
hepatitis
Immune-related
nephritis and renal
dysfunction
Immune-related
rash
Immune-related
endocrinopathies
Grade 2 elevation Withhold Nivolumab until values return to baseline,
is AST, ALT or
and corticosteroids are complete.
bilirubin
If values are persistently high, give corticosteroids
at a dose of 0.5 to 1 mg/kg/day methylprednisolone
IV or oral equivalent. Upon improvement, taper
corticosteroid and resume Nivolumab. If worsening
or no improvement despite corticosteroids,
increase dose to 1 to 2 mg/kg/day
methylprednisolone IV or oral equivalent and
permanently discontinue Nivolumab.
Grade 3 or 4
Permanently discontinue Nivolumab. Initiate
elevation is AST, corticosteroids at a dose of 1 to 2 mg/kg/day
ALT or bilirubin
methylprednisolone IV or oral equivalent.
Grade 2 or 3
Withhold Nivolumab until creatinine returns to
creatinine
baseline. Initiate corticosteroids at a dose of 0.5 to
increase
1 mg/kg/day methylprednisolone IV or oral
equivalent. Upon improvement, taper corticosteroid
and resume Nivolumab. If worsening or no
improvement, increase corticosteroids to 1 to 2
mg/kg/day methylprednisolone IV or oral
equivalent, and permanently discontinue
Nivolumab.
Grade 4
permanently discontinue Nivolumab. Initiate
creatinine
corticosteroids at a dose of 1 to 2 mg/kg/day
increase
methylprednisolone IV or oral equivalent.
Grade 3
Withhold Nivolumab until symptoms resolve and
management with corticosteroids is complete. In
severe rash, initiate corticosteroids at a dose of 1
to 2 mg/kg/day methylprednisolone IV or oral
equivalent. If immunosuppression with
corticosteroids is used to treat an immune-related
rash, a taper of at least 1 month duration should be
initiated upon improvement.
Grade 4
Manage the same as grade 3, however
permanently discontinue Nivolumab.
Symptomatic grade 2 or 3
hypothyroidism,
hyperthyroidism, hypophysitis
Grade 2 adrenal insufficiency
Grade 3 diabetes
Grade 4 hypothyroidism,
hyperthyroidism,
hypophysitis,
diabetes
Grade 3 or 4 adrenal
insufficiency
.
nivolumab for melanoma and rcc s16 004
Issue Date: 31 October 2014
Withhold Nivolumab until symptoms
resolve and management with
corticosteroids is complete.
Permanently discontinue Nivolumab
Page 4 of 5
Expiry Date: 31 October 2016
NECN CHEMOTHERAPY HANDBOOK PROTOCOL
Cumbria, Northumberland, Tyne & WearArea Team
Non- Haematological Toxicity:
No dose adjustment for mild hepatic impairment. Nivolumab must be administered with
caution in patients with moderate (total bilirubin > 1.5 x to 3 x the upper limit of normal [ULN]
and any AST) or severe (total bilirubin > 3 x ULN and any AST) hepatic impairment
No dose adjustment is required in patients with mild to moderate renal impairment. Data
from patients with severe renal impairment are too limited to draw conclusions on this
population.
TREATMENT LOCATION
Can be given at Cancer Centre or Cancer unit
REFERENCES
 Summary of Product Characteristics: Nivolumab (Opdivo®)
https://www.medicines.org.uk/emc/medicine/30602 Accessed 04/11/16.
 Nivolumab for treating advanced (unresectable or metastatic) melanoma. NICE
technology appraisal guidance [TA384] Published date: 18 February 2016
 Nivolumab in combination with ipilimumab for treating advanced melanoma. NICE
technology appraisal guidance [TA400] Published date: 27 July 2016
 Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus Everolimus in
Advanced Renal-Cell Carcinoma. N Engl J Med. 2015;373(19):1803–1
 Brahmer J, Reckamp K, BaasP et al. Nivolumab versus Docetaxel in Advanced
Squamous-Cell Non-Small-Cell Lung Cancer. NEJM. 2015. 373(2): 123-135.
EXTRAVASATION See NECN/Local Policy
Document Control
Document Title:
Nivolumab for Melanoma and RCC S16 004
Document No:
CHEMO S16 004
Current
Version:
1.0
Authors:
Gina Kilvington (pre-registration
Pharmacist, Northumbria
Approved
by:
Steve Williamson
Consultant Pharmacist, NHS England
Approval
Date
04.11.16
Review
Date
04.11.18
Summary of
Changes
nivolumab for melanoma and rcc s16 004
Issue Date: 31 October 2014
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Expiry Date: 31 October 2016