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Ou SH et al. J Clin Oncol. 2016;34:661–668

FDA and EMA prescribing information and miscellaneous sources

 

Alectinib 600 mg/dose; administer orally twice daily (approximately every 12 hours) with food, continually (total dose/week = 8400 mg)

 

Notes:

  • Patients who delay taking alectinib at a regularly scheduled time or who vomit after taking a dose of alectinib should take the next dose at the next regularly scheduled time

  • Alectinib may cause photosensitivity. Counsel patients to apply sunscreen and avoid prolonged sun exposure during treatment and for a minimum of 7 days following the last dose of alectinib

 

Supportive Care

Antiemetic prophylaxis

Emetogenic potential is LOW

See Chapter 39 for antiemetic recommendations

 

Hematopoietic growth factor (CSF) prophylaxis

Primary prophylaxis is NOT indicated

See Chapter 43 for more information

 

Antimicrobial prophylaxis

Risk of fever and neutropenia is LOW

  • Antimicrobial primary prophylaxis to be CONSIDERED:

    • Antibacterial—not indicated

    • Antifungal—not indicated

    • Antiviral—not indicated unless patient previously had an episode of HSV

See Chapter 47 for more information

 

Patient Population Studied

A multicenter, single-arm, phase 2 study involved 138 patients with crizotinib-refractory, locally advanced or metastatic, ALK-rearranged non-small-cell lung cancer. Eligible patients were aged ≥18 years, with an Eastern Cooperative Oncology Group (ECOG) performance status score ≤2. All patients received 600 mg alectinib twice daily

 

Efficacy (N = 122)

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Objective response rate 50%
Median duration of response 11.2 months
Median progression-free survival 8.9 months

Overall response rate is the percentage of patients who experienced a confirmed partial or complete response to the study drug

 

Therapy Monitoring

  1. Monitor liver function tests, including ALT, AST, and total bilirubin, every 2 weeks during the first 3 months of treatment, then once a month and as clinically indicated, with more frequent testing in patients who develop transaminase and bilirubin elevations

  2. Promptly investigate for ILD/pneumonitis in any patient who presents with worsening of respiratory symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, and fever)

  3. Monitor renal function at least monthly during entire duration of drug administration. The median time to grade ≥3 renal impairment in clinical trials was 3.7 months (range 0.5–14.7 months)

  4. Monitor heart rate and blood pressure regularly

  5. Advise patients to report any unexplained muscle pain, tenderness, or weakness. Assess CPK levels every 2 weeks for the first month of treatment and as clinically indicated in patients reporting symptoms

 

Treatment Modifications

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Dose Reduction Schedule Dose Level
Starting dose 600 mg taken orally twice daily
Dose level −1 450 mg taken orally twice daily
Dose level −2 300 mg taken orally twice daily
Dose level −3 Discontinue alectinib
Adverse Event Dose Modification
≥G3 ALT or AST elevation [>5 times ULN] + total bilirubin ≤2× ULN Withhold alectinib until recovery to baseline or ALT and AST ≤3× ULN, then resume alectinib but reduce the dose by 150 mg
≥G2 ALT or AST elevation [>3 times ULN] + total bilirubin >2× ULN Permanently discontinue alectinib
Total bilirubin elevation of >3× ULN Temporarily withhold alectinib until recovery to baseline or to ≤1.5× ULN, then resume at 1 lower dose level
Any grade treatment-related ILD/pneumonitis Permanently discontinue alectinib
G3 renal impairment Temporarily withhold alectinib until serum creatinine recovers to ≤1.5× ULN, then resume at 1 lower dose level
G4 renal impairment Permanently discontinue alectinib
Asymptomatic bradycardia Dose modification is not required
Symptomatic bradycardia Withhold alectinib until recovery to asymptomatic bradycardia or to a heart rate ≥60 bpm. If contributing concomitant, medication is identified and discontinued, or its dose is adjusted, resume alectinib at previous dose upon recovery to asymptomatic bradycardia or to a heart rate ≥60 bpm. If no contributing concomitant, medication is identified, or if contributing concomitant medications are not discontinued or dose modified, resume alectinib at 1 lower dose level upon recovery to asymptomatic bradycardia or to a heart rate ≥60 bpm
Life-threatening bradycardia requiring urgent intervention Permanently discontinue alectinib if no contributing concomitant medication is identified. If contributing concomitant, medication is identified and discontinued, or its dose is adjusted, resume alectinib at 1 lower dose level upon recovery to asymptomatic bradycardia or to a heart rate ≥60 bpm, with frequent monitoring as clinically indicated. Permanently discontinue alectinib in case of recurrence
CPK elevation >5× ULN Temporarily withhold alectinib until recovery to baseline or to ≤2.5× ULN, then resume at same dose
CPK elevation >10× ULN or second occurrence of CPK elevation of >5× ULN Temporarily withhold alectinib until recovery to baseline or to ≤2.5× ULN, then resume at 1 lower dose level
≥G2 constipation, fatigue, edema, myalgia, and anemia Temporarily withhold alectinib until recovery to baseline or to ≤G1, then resume at same dose

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CPK, creatine phosphokinase; ILD, interstitial lung disease; ULN, upper limit of normal

Notes:

  • Advise females of reproductive potential to use effective contraception during treatment with alectinib and for at least 2 weeks following completion of therapy

  • No dose adjustment is recommended for patients with mild or moderate renal impairment. The safety of alectinib in patients with creatinine clearance <30 mL/min has not been studied

  • No dose adjustment is recommended for patients with mild hepatic impairment. The safety of alectinib in patients with moderate or severe hepatic impairment has not been studied

 

Adverse Events (N = 138)

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Grade (%) Grade 1 Grade 2 Grade 3 Grade 4
Myalgia 14 2 1 0
Constipation 12 2 0 0
Fatigue 12 1 1 0
Asthenia 9 1 1 0
Elevated AST level 8 1 1 1
Elevated ALT level 4 4 1 1
Peripheral edema 7 1 1 0
Rash 8 1 0 0
Photosensitivity reaction 9 0 0 0
Elevated bilirubin level 1 5 1 0
Nausea 5 1 0 0
Diarrhea 4 0 1 0
Dry skin 5 0 0 0

According to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0

Notes: Toxicities included in the table are those deemed to have been related to treatment and to have occurred in ≥5% of patients. No treatment-related deaths occurred

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