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OSIM

Cancer Type: Lung, Non-Small Cell  Intent: Palliative
Regimen Category: Evidence-Informed
Funding:
Exceptional Access Program
    Osimertinib - Second-line monotherapy of patients with locally advanced or metastatic EGFR T790M mutation-positive non-small cell lung cancer, according to specific criteria
A - Regimen Name

OSIM Regimen
Osimertinib


Disease Site
Lung - Non-Small Cell

Intent
Palliative

Regimen Category
Evidence-Informed :

Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR).  Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.


Rationale and Uses

For the treatment of patients with locally advanced or metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC) who have progressed on or after EGFR tyrosine kinase inhibitor therapy.

 


Supplementary Public Funding

osimertinib
Exceptional Access Program (Osimertinib - Second-line monotherapy of patients with locally advanced or metastatic EGFR T790M mutation-positive non-small cell lung cancer, according to specific criteria) (EAP Website)

 
B - Drug Regimen

osimertinib
80 mg PO Daily

(available as 40mg and 80 mg tablets)

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C - Cycle Frequency

CONTINUOUS TREATMENT

Until disease progression or unacceptable toxicity.

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

Minimal

Consider recommending the regular application of moisturizers to skin and nails to prevent and control skin and nail adverse effects.

 
E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated. The following recommendations have been adapted from clinical trials or product monographs and may be considered. A validated test to confirm EGFR T790M mutation status should be conducted before starting treatment. Electrolyte abnormalities should be corrected prior to treatment.

 

Dosage with toxicity

Toxicity Dose modfication
ILD/pneumonitis Hold and investigate. Discontinue permanently if confirmed.
QTc interval > 500 msec on at least 2 separate ECGs

Hold until QTc interval is < 481 msec or recovery to baseline if baseline is ≥ 481 msec.
Then restart at a reduced dose (40 mg).

Asymptomatic LVEF < 50% and absolute decrease of 10% from baseline

Hold for up to 4 weeks.

If recovery to baseline, restart.
If no recovery to baseline, discontinue permanently.

QTc interval prolonged with signs/symptoms of serious arrhythmia (e.g. Torsade de pointes, polymorphic VT)

OR Symptomatic congestive heart failure

Discontinue permanently.
Signs & symptoms suggestive of keratitis Refer promptly to an ophthlamology specialist. 
Other grade 3 or higher toxicity

Hold for up to 3 weeks.

If recovery to ≤ grade 2, restart at the same or lower dose (40 mg).
If no recovery, discontinue permanently.

 



Hepatic Impairment

Hepatic impairment Osimertinib dose
mild (total bilirubin ≤ ULN and AST > ULN OR total bilirubin 1-1.5 x ULN and any AST) no dosage adjustment required
moderate or severe no data; use with caution

Renal Impairment

Patients with CrCl < 15 ml/min or on dialysis were excluded from clinical trials.

Renal impairment Osimertinib dose
mild to moderate no dosage adjustment required
severe limited data; use with caution

Dosage in the Elderly

Dosage adjustment is not required as age did not have a significant effect on drug exposure.

 

Patients ≥65 years of age experienced more Grade ≥3 adverse reactions compared to younger (5% versus 2%, respectively in the AURA3 trial); however, no clinically meaningful differences in efficacy or pharmacokinetics based on age were observed.

Dosage based on ethnicity

In clinical trials, the incidence of ILD was higher in Japanese patients compared to other Asians and non-Asian patients (8% vs. 1.9% and 2.9%, respectively).

 


 
F - Adverse Effects

Refer to osimertinib drug monograph(s) for additional details of adverse effects


Very common (≥ 50%)

Common (25-49%)

Less common (10-24%)

Uncommon (< 10%),

but may be severe or life-threatening

n/a
  • Diarrhea
  • Rash, pruritus
  • Nail disorder
  • Nausea, vomiting
  • Anorexia
  • Constipation
  • Cough, dyspnea
  • Nasopharyngitis
  • Fatigue
  • Musculoskeletal pain
  • Mucositis
  • Headache
  • QT interval prolonged
  • Cardiotoxicity
  • Arterial/venous thromboembolism
  • Myelosuppression +/- infection, bleeding
  • Keratitis, blurred vision
  • Pneumonitis
  • BOOP
  • Increased LFTs 
 
G - Interactions

Refer to osimertinib drug monograph(s) for additional details


  • Avoid co-administration with strong CYP3A4 inducers as reduced osimertinib concentration and/or efficacy is possible
  • Avoid co-administration with CYP3A and BCRP substrates with narrow therapeutic indices given increased risk of substrate toxicity
  • Reduced effectiveness of oral hormonal contraceptives is possible. Consider alternative contraception.
  • Avoid drugs that may prolong the QT interval and those that may disrupt electrolyte levels given increased risk of QT prolongation
 
H - Drug Administration and Special Precautions

Refer to osimertinib drug monograph(s) for additional details


Administration

  • Osimertinib may be taken with or without food at the same time each day
  • The tablet should be swallowed whole with water and not crushed, split or chewed
  • If a dose is missed, it may be taken within 12 hours. If there are less than 12 hours until the next dose, the missed dose should be skipped and the next dose should be taken at the scheduled time.
  • If the patient has difficulty swallowing, the tablet may be dispersed in 50 ml of non-carbonated water and swallowed immediately. An additional 50 ml of water should be added to capture drug residue and immediately swallowed.
  • Store tablets at room temperature (15-30oC)

Contraindications

  • Patients who are hypersensitive to this drug or to ingredients in the formulation or component in the container

Other Warnings/Precautions

  • Not recommended in patients with congenital long QT syndrome or those taking other medications know to prolong QTc
  • Patients at risk for prolonged QTc such as those with cardiac disease, history of arrhythmias, electrolyte disturbances or conditions leading to electrolyte disturbances, bradycardia, acute neurological events, diabetes mellitus and autonomic neuropathy should be monitored closely and electrolyte abnormalities corrected prior to treatment.
  • Patients with abnormal LVEF or those with significant cardiac history were excluded from clinical trials.
  • Patients with a history of ILD/pneumonitis, evidence of clinically active ILD or those with radiation pneumonitis requiring steroids were excluded from clinical trials.
  • Ocular events have been reported. Contact lens use is risk factor for ocular toxicity, including keratitis. Caution should be used when driving or operating machinery in patients who experience visual disturbances.

Pregnancy and lactation

  • Osimertinib is not recommended for use in pregnancy.  Adequate contraception (including a barrier method in females using hormonal contraception) should be used by both sexes during treatment, and for at least 2 months after the last dose (for females) and 4 months after the last dose (for males).
  • Breastfeeding is not recommended.
 
I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Recommended Clinical Monitoring

  • CBC; Baseline and at each visit
  • ECG and electrolytes (calcium, potassium and magnesium), especially in patients at risk of electrolyte abnormalities; Baseline and as clinically indicated
  • Liver function tests; Baseline and at each visit
  • LVEF; Baseline and every 12 weeks during treatment for patients with cardiac risk factors and those who develop cardiac signs/symptoms during treatment.
  • Renal function tests; Baseline and at each visit; more frequent in patients with severe renal impairment
  • Clinical toxicity assessment for GI, skin and respiratory effects, signs and symptoms of CHF, infection, bleeding, thromboembolism and ocular effects; At each visit
  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version


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J - Administrative Information

Outpatient prescription for home administration


 
K - References

Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, et al.; AURA3 Investigators. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017 Feb 16;376(7):629-640.

Osimertinib drug monograph, Cancer Care Ontario.


October 2018 Added EAP funding information


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M - Disclaimer

Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph.  Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
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