BC Cancer Protocol Summary for Adjuvant Treatment of

Epidermal Growth Factor Receptor (EGFR) Mutation-Positive

Non-Small Cell Lung Cancer (NSCLC) with Osimertinib
Protocol Code: LUAJOSI

Tumour Group: Lung

Contact Physician: Dr. Sophie Sun

ELIGIBILITY:
Patients must have:
 Surgically resected stage IB to IIIB NSCLC (per American Joint Committee on
Cancer (AJCC) 8th edition),
 EGFR mutation-positive tumour with exon 19 or L858R mutation, and
 Eligible with or without post-operative chemotherapy:
 Surgical resection within 12 weeks of starting osimertinib treatment if no
adjuvant chemotherapy administered
 Surgical resection within 28 weeks of starting osimertinib treatment if
adjuvant chemotherapy was administered

Patients should have:

 ECOG 0-2

EXCLUSIONS:
Patients must not have:
 Congenital long QT syndrome or a persistent corrected QT interval (QTc) of ≥
470 msec

TESTS:
 Baseline: CBC & differential, platelets, creatinine, alkaline phosphatase, ALT,
total bilirubin, LDH, calcium, potassium, magnesium, and ECG
 During treatment: alkaline phosphatase, ALT, total bilirubin, LDH, potassium,
calcium and magnesium at each subsequent visit
 As required:
 CBC & differential, platelets
 MUGA scan or echocardiogram – if clinically indicated, monitoring of
LVEF is recommended at baseline and at 12-week intervals
 periodic ECG monitoring for QTc prolongation
 creatinine if clinically indicated
 chest x-ray for monitoring of dyspnea to rule out development of
pneumonitis

PREMEDICATIONS:
 no premedications required

BC Cancer Protocol Summary LUAJOSI Page 1 of 3

Activated: 1 Feb 2023 Revised: 1 Mar 2023 (drug name clarified)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician
seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of
these documents is at your own risk and is subject to BC Cancer’s terms of use available at www.bccancer.bc.ca/terms-of-use
TREATMENT:

Drug Dose BC Cancer Administration Guideline

osimertinib 80 mg once daily PO

• For patients with difficulty swallowing, or for nasogastric tube administration, please refer to
the BC Cancer Drug Manual osimertinib drug monograph

Continue until disease progression, unacceptable toxicity or a maximum of 3 years

of treatment.

DOSE MODICATIONS:

Dose reduction:
Dose level -1: osimertinib 40 mg PO once daily

1. Renal Impairment: dose modification is not required in patients with mild or

moderate renal impairment. Safety and efficacy has not been established in
patients with end-stage renal disease (CrCl < 15 mL/min) or on dialysis.
2. Hepatic Impairment: dose modification is not required in patients with mild
hepatic impairment. Safety and efficacy has not been established in patients
with moderate or severe hepatic impairment.
3. Interstitial Lung Disease (ILD): permanently discontinue osimertinib for
development of any grade of treatment-related ILD/pneumonitis.
4. QT Prolongation: treatment interruption and subsequent dose reduction is
required for development of QTc prolongation (QTc > 500 msec on at least two
separate ECGs). Withhold osimertinib until QTc interval is less than 481 msec
or recovery to baseline if baseline QTc is greater than or equal to 481 msec,
then restart at a reduced dose (40 mg). If QTc interval prolongation with
signs/symptoms of serious arrhythmia, permanently discontinue osimertinib.
5. Left Ventricular Dysfunction/Cardiomyopathy: treatment interruption is
recommended for asymptomatic, absolute decreases in LVEF of 10% from
baseline and LVEF below 50%. If symptomatic congestive heart failure occurs
at any time, treatment should be permanently discontinued.

PRECAUTIONS:

1. Cardiomyopathy: congestive heart failure, pulmonary edema, and decreased

ejection fraction have been observed in patients treated with osimertinib. Fatal
cardiomyopathy has been reported. LVEF should be assessed regularly during
treatment, particularly in patients with known cardiac risk factors, and in
patients who develop treatment-related cardiac symptoms.
2. QT Interval Prolongation: osimertinib is associated with concentration-
dependent QT interval prolongation. Monitor ECG at baseline and correct
BC Cancer Protocol Summary LUAJOSI Page 2 of 3
Activated: 1 Feb 2023 Revised: 1 Mar 2023 (drug name clarified)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician
seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of
these documents is at your own risk and is subject to BC Cancer’s terms of use available at www.bccancer.bc.ca/terms-of-use
 electrolyte abnormalities prior to treatment. Continued monitoring of ECG and
electrolytes is recommended during treatment, particularly in patients with
predisposing conditions, and in those receiving concomitant drugs known to
prolong the QT interval.
3. Respiratory: osimertinib has been associated with severe, life-threatening or
fatal treatment-related interstitial lung disease/pneumonitis. Patients should be
regularly monitored for pulmonary symptoms indicative of pneumonitis.
4. Ocular Disorders: osimertinib has been associated with keratitis,
conjunctivitis, blepharitis, and dry eye. Ophthalmologic consultation should be
considered for associated symptoms. Contact lens use is known to be an
independent risk factor for ocular toxicity, including keratitis. Caution should be
exercised when driving or operating machinery.
5. Drug interactions: concurrent use of strong CYP3A inducers should be
avoided. If possible, concurrent therapy with drugs that prolong the QTc interval
or disrupt electrolyte levels should also be avoided.
6. Skin toxicity: rash, including dermatitis acneiform, drug eruption, folliculitis,
rash erythematous and maculopapular are common. They appear on the face,
scalp, “v”-shaped area of the chest, upper trunk and less frequently on the
extremities, lower back, abdomen and buttocks. Severe rashes may require
dose interruption and modification.
7. Paronychia: osimertinib is associated with paronychia, which typically occurs
later in treatment (e.g., 4-8 weeks) and can cause severe pain. Preventative
measures and good skin care may help to reduce the frequency and severity of
symptoms.

Contact Dr. Sophie Sun or tumour group delegate at (604) 930-2098 or 1-800-
663-3333 with any problems or questions relating to this treatment program.

References:
1. Wu YL, Tsuboi M, He J, et al. Osimertinib in Resected EGFR-Mutated Non-
Small-Cell Lung Cancer. N Engl J Med. 2020 Oct 29;383(18):1711-1723.
2. Planchard D. Adjuvant Osimertinib in EGFR-Mutated Non-Small-Cell Lung
Cancer. N Engl J Med. 2020 Oct 29;383(18):1780-1782.

BC Cancer Protocol Summary LUAJOSI Page 3 of 3

Activated: 1 Feb 2023 Revised: 1 Mar 2023 (drug name clarified)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician
seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of
these documents is at your own risk and is subject to BC Cancer’s terms of use available at www.bccancer.bc.ca/terms-of-use