BC Cancer Protocol Summary for Treatment of ALK-Positive

Advanced Non-Small Cell Lung Cancer (NSCLC) with Alectinib

Protocol Code: LUAVALE

Tumour Group: Lung

Contact Physician: Dr. Christopher Lee

ELIGIBILITY:
Patients must have:
 Advanced non-small cell lung cancer,
 Laboratory confirmed anaplastic lymphoma kinase (ALK)-positive tumour defined as
either IHC 3+, FISH positive, or positive by molecular testing (next-generation
sequencing), and
 One of the following indications:
o First-line monotherapy. Patients are eligible to receive one of: alectinib, lorlatinib,
crizotinib or brigatinib. Switching for intolerance is permitted. OR
o Second-line monotherapy for disease progression on crizotinib, or in patients with
intolerance to crizotinib

Patients should have:

 ECOG 0 to 2

EXCLUSIONS:
Patients must not have:
 ROS1 mutation
 Baseline symptomatic bradycardia or QTc interval greater than 470 msec
 Severe renal impairment with CrCl less than 30 mL/min
 Progression during treatment on previous ALK-targeted tyrosine kinase inhibitor
other than crizotinib

BC Cancer Protocol Summary LUAVALE Page 1 of 4

Activated: 1 May 2019 Revised: 1 Oct 2024 (Tests updated)
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
TESTS:
 Baseline: alkaline phosphatase, ALT, total bilirubin, LDH, heart rate, blood pressure
 C-reactive protein and albumin (optional, and results do not have to be
available to proceed with first treatment)
 Baseline, if clinically indicated: ECG
 During treatment:
 alkaline phosphatase, ALT, total bilirubin and LDH should be monitored every
2 weeks for the first three months of treatment, and at each subsequent visit
thereafter
 CPK levels should be monitored every 2 weeks for the first month of
treatment and as clinically indicated thereafter
 If clinically indicated: calcium, potassium, ECG, heart rate, blood pressure,
creatinine, CPK, chest radiograph for monitoring of dyspnea to rule out development
of pneumonitis; chest X-ray and scans to monitor index lesions.

PREMEDICATIONS:
 no premedications needed

TREATMENT:
Drug Dose BC Cancer Administration Guideline

alectinib 600 mg twice daily PO

Hepatic Impairment: in patients with underlying severe hepatic impairment the

recommended starting dose is 450 mg PO twice daily
Dose reduction:
Dose level -1: 450 mg twice daily
Dose level -2: 300 mg twice daily
 Careful re-evaluation after initiation of therapy is essential as alectinib should be
continued only if tumour regression continues or the disease is stable and cancer-
related symptoms have improved. Continued alectinib for “psychological” palliation in
the face of progressive disease is inappropriate.

DOSE MODICATIONS:
1. Hepatic Dysfunction:
ALT elevation to > 5.0 x ULN with Withhold until recovery of ALT to ≤ 3.0
bilirubin ≤ 2 x ULN x ULN or baseline, then resume at
reduced dose
ALT elevation to > 3.0 x ULN and
concurrent bilirubin elevation to > 2 Permanently discontinue
x ULN (in absence of cholestasis
or hemolysis)

BC Cancer Protocol Summary LUAVALE Page 2 of 4

Activated: 1 May 2019 Revised: 1 Oct 2024 (Tests updated)
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
2. Renal dysfunction: treatment interruption and subsequent dose reduction is
required for development of grade 3 renal impairment. Permanently discontinue for
development of grade 4 renal impairment. Refer to BC Cancer Drug Manual.
3. Bradycardia: for symptomatic, non-life threatening bradycardia, withhold treatment
until asymptomatic or heart rate increases to ≥ 60 bpm. Permanently discontinue for
recurrent life-threatening bradycardia or life-threatening bradycardia which occurs in
the absence of concurrent bradycardic/hypotensive medications. Refer to BC
Cancer Drug Manual.
4. Myalgia/CPK Elevation: treatment interruption may be required for symptom
management or for elevation of CPK to > 5 x ULN. Refer to BC Cancer Drug
Manual.
5. Pneumonitis: permanently discontinue alectinib for development of any grade of
treatment-related pneumonitis.
6. Gastrointestinal perforation: permanently discontinue alectinib for development of
gastrointestinal perforation.

PRECAUTIONS:
1. Cardiotoxicity: Bradycardia, both symptomatic and asymptomatic, has been
observed in patients treated with alectinib. Heart rate and blood pressure should be
monitored regularly during treatment and co-administration of medications that lower
heart rate should be avoided to the extent possible. If avoidance is not possible,
patients should be closely monitored. Caution should be exercised in patients with a
lower baseline heart rate, history of syncope or arrhythmia, sick sinus syndrome,
sinoatrial block, atrioventricular (AV) block, ischemic heart disease, or congestive
heart failure. Cardiology consult may be required.
2. Gastrointestinal Perforation: Gastrointestinal perforation with fatal outcome, has
occurred in <1% of patients treatment with alectinib. Exercise caution in patients at
increased risk for gastrointestinal perforation – concomitant use of medications with
risk of gastrointestinal perforation, history of diverticulitis, metastases to the
gastrointestinal tract. Alectinib should be permanently discontinued in patients who
develop gastrointestinal perforation.
3. Respiratory: Alectinib has been associated with cases of ILD/pneumonitis. Patients
should be regularly monitored throughout treatment for pulmonary symptoms
indicative of pneumonitis.
4. Hepatic Impairment: Patients with underlying severe hepatic impairment should
receive a dose reduction of alectinib. Dose adjustment is not required for patients
with underlying mild or moderate hepatic impairment. However, for all patients with
hepatic impairment, appropriate monitoring is advised.
5. Hepatotoxicity: Bilirubin and transaminase elevations have been reported and
generally occur within the first three months of treatment. Elevations are usually
reversible with treatment interruption/dose reduction. However, biopsy confirmed
drug-induced liver injury has occurred in some patients. Monitor liver function
regularly during treatment and increase test frequency if clinically indicated.

BC Cancer Protocol Summary LUAVALE Page 3 of 4

Activated: 1 May 2019 Revised: 1 Oct 2024 (Tests updated)
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
6. Musculoskeletal: Myalgia can sometimes be severe and may be associated with
elevated creatine phosphokinase (CPK). Management of symptoms may require
alectinib dose modification or temporary discontinuation of treatment.
7. Photosensitivity: Photosensitivity has been reported. Prolonged sun exposure
should be avoided. If exposure is unavoidable, broad-spectrum sun screen and lip
balm of at least SPF 50 should be used during treatment and for seven days after
discontinuation of treatment.
8. Vision disorders: Diplopia, blurry vision, vitreous floaters, asthenopia, and reduced
visual acuity have all been reported. Patients experiencing vision disorders should
be cautious when driving or operating machinery.

Call Dr. Christopher Lee or tumour group delegate at (604) 877-6000 or 1-

800-663-3333 with any problems or questions relating to this treatment
program.

References:
1. Hoffman-La Roche Ltd. Alectinib (ALECENSARO®) product monograph. Mississauga, Ontario: 27
September 2016.
2. Peters S, Camidge R, Shaw A et al. Alectinib vs Crizotinib in Untreated ALK-Positive Non-Small
Cell Lung Cancer. NEJM 2017; 377: 829-38.
3. Hida T, Nokihara H, Kondo M, et al. Alectinib vs Criztonib in Patients with ALK-Positive Non-Small
Cell Lung Cancer (J-ALEX): an open-label, randomized phase 3 trial. Lancet 2017 July;
390(10089): 29-39.

BC Cancer Protocol Summary LUAVALE Page 4 of 4

Activated: 1 May 2019 Revised: 1 Oct 2024 (Tests updated)
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