For Patients and Caregivers

Prescribing Information

ALECENSA® (alectinib) Has a Well-Established Safety Profile

Primary Analysis

Overall fewer Grade 3/4 adverse reactions occurred with ALECENSA compared with crizotinib2

Adverse Drug Reactions (>10% for all NCI CTCAE Grades or ≥2% for Grades 3-4) in Patients Treated With ALECENSA in ALEX2

Adverse Drug Reactions in Patients Treated with ALECENSA® (alectinib) or Crizotinib

aIncludes fatigue and asthenia.
bIncludes myalgia and musculoskeletal pain.
cIncludes peripheral edema, edema, eyelid edema, localized edema, and face edema.
dIncludes rash, rash maculo-papular, dermatitis acneiform, erythema, generalized rash, rash macular, rash papular, exfoliative rash, and pruritic rash.
eIncludes increased blood creatinine, creatinine renal clearance decreased, glomerular filtration rate decreased, and acute kidney injury.
fIncludes reported cases of bradycardia and sinus bradycardia but is not based on serial ECG assessment.
gIncludes 2 Grade 5 events.

Fewer dose reductions, interruptions, and discontinuations due to adverse reactions occurred with ALECENSA vs crizotinib2,3

Safety Overview in Primary Analysis2,3

Primary Safety Overview With ALECENSA® (alectinib) or Crizotinib

hAll unrelated to treatment.3
iTwo related to treatment.3

Most frequent adverse reactions (≥2%) leading to a dose modification for ALECENSA4

  • Dose reduction: elevated ALT (2%), elevated AST (3.3%), elevated bilirubin (2%), anemia (2%), and hyperbilirubinemia (2%)
  • Dose interruption: ALT increased (3%) and AST increased (2%)
  • Permanent discontinuation: renal impairment (2%)

Laboratory Abnormalities Occurring in >10% of Patients Treated With ALECENSA or Crizotinib2j

Laboratory Abnormalities Occurring in Patients Treated with ALECENSA® (alectinib) or Crizotinib

Note: Based on NCI CTCAE v4.03. Excludes patients with no post-baseline lab assessments.

jPatients with missing baseline values were included. For each laboratory abnormality, the number of patients evaluated may vary (n=131 to n=148). Please refer to PI for additional information.2

Consistent Safety Profile Observed at Follow-Up2,3,15

Follow-Up Analysis heading

Safety Overview in Follow-Up Analysis15

Follow-Up Safety Overview With ALECENSA® (alectinib) or Crizotinib
Safety Results at 5 Year Post-Hoc Analysis for ALECENSA

The median duration of exposure to ALECENSA was 28.1 months (range: 0-77 months)4

jAll unrelated to treatment.19
lTwo related to treatment.19

1L=first-line; ALT=alanine transaminase; AST=aspartate transaminase; CNS=central nervous system; CPK=creatine phosphokinase; ECG=electrocardiogram; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events; PFS=progression-free survival.

Next: Post-Crizotinib Treatment
1L PFS Results icon

1L PFS Results

View PFS results vs crizotinib from the head-to-head ALEX trial.

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1L Primary & Exploratory 5-Year OS Data icon

1L Primary & Exploratory
5-Year OS Data

View exploratory landmark analysis.

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CNS protection icon

CNS Efficacy in 1L ALK+ mNSCLC

Learn more about CNS efficacy with ALECENSA.

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Dosing and Administration icon

Dosing and Administration

Learn about dosing and monitoring for ALECENSA.

View ALECENSA Dosing

Important Safety Information & Indications

Indications

ALECENSA is a kinase inhibitor indicated for:

  • adjuvant treatment in adult patients following tumor resection of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) (tumors ≥4 cm or node positive), as detected by an FDA-approved test
  • treatment of adult patients with ALK-positive metastatic NSCLC as detected by an FDA-approved test

Warnings and Precautions

Hepatotoxicity

  • Severe hepatotoxicity, including drug-induced liver injury, occurred in patients treated with ALECENSA. Hepatotoxicity occurred in 41% of 533 patients treated with ALECENSA and the incidence of Grade ≥3 hepatotoxicity was 8%. In the ALINA study, hepatotoxicity occurred in 61% of patients treated with ALECENSA and the incidence of Grade ≥3 hepatotoxicity was 4.7%. The majority (72% of 136 patients) of elevated transaminases occurred during the first 3 months of treatment. Treatment discontinuation due to hepatotoxicity occurred in 3.6% of patients who received ALECENSA in the pooled safety population and 1.6% of patients treated in the ALINA study
  • Concurrent elevations in alanine transaminase (ALT) or aspartate transaminase (AST) greater than or equal to 3 times the ULN and total bilirubin greater than or equal to 2 times the ULN, with normal alkaline phosphatase, occurred in less than 1% of patients treated with ALECENSA. Three patients with Grades 3-4 AST/ALT elevations had drug-induced liver injury (documented by liver biopsy in 2 cases)
  • 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. Based on the severity of the adverse drug reaction, withhold ALECENSA and resume at a reduced dose, or permanently discontinue ALECENSA

Interstitial Lung Disease (ILD)/Pneumonitis

  • ILD/pneumonitis occurred in 1.3% of 533 patients treated with ALECENSA with 0.4% of patients experiencing Grade 3 ILD/pneumonitis. Five patients (0.9%) discontinued ALECENSA due to ILD/pneumonitis. The median time-to-onset of Grade 3 or higher ILD/pneumonitis was 2.1 months (range: 0.6 months to 3.6 months)
  • Promptly investigate for ILD/pneumonitis in any patient who presents with worsening of respiratory symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, and fever)
  • Immediately withhold ALECENSA treatment in patients diagnosed with ILD/pneumonitis and permanently discontinue ALECENSA if no other potential causes of ILD/pneumonitis have been identified

Renal Impairment

  • Renal impairment occurred in 12% of 533 patients treated with ALECENSA, including Grade ≥3 in 1.7% of patients, of which 0.4% were fatal events
  • The median time to Grade ≥3 renal impairment was 3.7 months (range 0.5 to 31.8 months). Dosage modifications for renal impairment were required in 2.4% of patients
  • Permanently discontinue ALECENSA for Grade 4 renal toxicity. Withhold ALECENSA for Grade 3 renal toxicity until recovery to less than or equal to 1.5 times ULN, then resume at reduced dose

Bradycardia

  • Symptomatic bradycardia occurred in patients treated with ALECENSA. Bradycardia occurred in 11% of 533 patients treated with ALECENSA. Twenty percent of 521 patients for whom serial electrocardiograms (ECGs) were available had post-dose heart rates of less than 50 beats per minute (bpm)
  • Monitor heart rate and blood pressure regularly. For asymptomatic bradycardia, dose modification is not required. For symptomatic bradycardia that is not life-threatening, withhold ALECENSA until recovery to asymptomatic bradycardia or to a heart rate ≥60 bpm and evaluate concomitant medications known to cause bradycardia, as well as anti-hypertensive medications. If bradycardia is attributable to a concomitant medication, resume ALECENSA at a reduced dose upon recovery to asymptomatic bradycardia or to a heart rate of ≥60 bpm, with frequent monitoring as clinically indicated
  • Permanently discontinue ALECENSA in cases of life-threatening bradycardia if no contributing concomitant medication is identified or for recurrence of life-threatening bradycardia

Severe Myalgia and Creatine Phosphokinase (CPK) Elevation

  • Severe myalgia and creatine phosphokinase (CPK) elevation occurred in patients treated with ALECENSA. Myalgia (including muscle- and musculoskeletal-related reactions) occurred in 31% of 533 patients treated with ALECENSA, including Grade ≥3 in 0.8% of patients. Dosage modifications for myalgia events were required in 2.1% of patients
  • Of the 491 with CPK laboratory data available, elevated CPK occurred in 56% of patients, including 6% Grade ≥3. The median time to Grade ≥3 CPK elevation was 15 days (interquartile range 15-337 days). Dosage modifications for elevation of CPK occurred in 5% of patients. In the ALINA study, elevated CPK occurred in 77% of 128 patients with CPK laboratory data, including 6% Grade ≥3 elevations
  • 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. Based on the severity of the CPK elevation, withhold ALECENSA, then resume or reduce dose

Hemolytic Anemia

  • Hemolytic anemia occurred in patients treated with ALECENSA. Hemolytic anemia was initially reported with ALECENSA in the postmarketing setting, including cases associated with a negative direct antiglobulin test (DAT) result. Assessments for the determination of hemolytic anemia were subsequently collected in the ALINA study, where hemolytic anemia was observed in 3.1% of patients treated with ALECENSA
  • If hemolytic anemia is suspected, withhold ALECENSA and initiate appropriate laboratory testing. If hemolytic anemia is confirmed, consider resuming at a reduced dose upon resolution or permanently discontinue ALECENSA

Embryo-Fetal Toxicity

  • ALECENSA can cause fetal harm when administered to pregnant women. Administration of alectinib to pregnant rats and rabbits during the period of organogenesis resulted in embryo-fetal toxicity and abortion at maternally toxic doses with exposures approximately 2.7-fold those observed in humans with alectinib 600 mg twice daily. Advise pregnant women of the potential risk to a fetus
  • Advise females of reproductive potential to use effective contraception during treatment with ALECENSA and for 5 weeks following the last dose
  • Advise males with female partners of reproductive potential to use effective contraception during treatment with ALECENSA and for 3 months following the last dose

Most Common Adverse Reactions

  • The most common adverse reactions (≥20%) were hepatotoxicity (41%), constipation (39%), fatigue (36%), myalgia (31%), edema (29%), rash (23%), and cough (21%)

Use in Specific Populations

Lactation

  • Because of the potential for serious adverse reactions in breastfed infants from ALECENSA, advise a lactating woman not to breastfeed during treatment with ALECENSA and for 1 week after the last dose

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see additional Important Safety Information in full Prescribing Information.

    • IQVIA US Claims, December 2022–March 2024.

      IQVIA US Claims, December 2022–March 2024.

    • ALECENSA [prescribing information]. South San Francisco, CA: Genentech USA, Inc. 2024.

      ALECENSA [prescribing information]. South San Francisco, CA: Genentech USA, Inc. 2024.

    • Peters S, Camidge DR, Shaw AT, et al. Alectinib versus crizotinib in untreated ALK-positive non–small cell lung cancer. N Engl J Med. 2017;377:829-838.

      Peters S, Camidge DR, Shaw AT, et al. Alectinib versus crizotinib in untreated ALK-positive non–small cell lung cancer. N Engl J Med. 2017;377:829-838.

    • Data on file. Genentech, Inc.

      Data on file. Genentech, Inc.

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.5.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed April 23, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org.

      Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.5.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed April 23, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org.

    • Carnio S, Novello S, Mele T, Levra MG, Scagliotti GV. Extending survival of stage IV non-small cell lung cancer. Semin Oncol. 2014;41:69-92.

      Carnio S, Novello S, Mele T, Levra MG, Scagliotti GV. Extending survival of stage IV non-small cell lung cancer. Semin Oncol. 2014;41:69-92.

    • Deeken JF, Löscher W. The blood-brain barrier and cancer: transporters, treatment, and Trojan horses. Clin Cancer Res. 2007;13:1663-1674.

      Deeken JF, Löscher W. The blood-brain barrier and cancer: transporters, treatment, and Trojan horses. Clin Cancer Res. 2007;13:1663-1674.

    • Silvestri GA, Gould MK, Margolis ML, et al. Noninvasive staging of non-small cell lung cancer: ACCP evidenced-based clinical practice guidelines (2nd edition). Chest. 2007;132(suppl):178S-201S.

      Silvestri GA, Gould MK, Margolis ML, et al. Noninvasive staging of non-small cell lung cancer: ACCP evidenced-based clinical practice guidelines (2nd edition). Chest. 2007;132(suppl):178S-201S.

    • Jena A, Taneja S, Talwar V, Sharma JB. Magnetic resonance (MR) patterns of brain metastasis in lung cancer patients: correlation of imaging findings with symptom. J Thorac Oncol. 2008;3:140-144.

      Jena A, Taneja S, Talwar V, Sharma JB. Magnetic resonance (MR) patterns of brain metastasis in lung cancer patients: correlation of imaging findings with symptom. J Thorac Oncol. 2008;3:140-144.

    • Sakamoto H, Tsukaguchi T, Hiroshima S, et al. CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell. 2011;19:679-690.

      Sakamoto H, Tsukaguchi T, Hiroshima S, et al. CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell. 2011;19:679-690.

    • Kodama T, Hasegawa M, Takanashi K, Sakurai Y, Kondoh O, Sakamoto H. Antitumor activity of the selective ALK inhibitor alectinib in models of intracranial metastases. Cancer Chemother Pharmacol. 2014;74:1023-1028.

      Kodama T, Hasegawa M, Takanashi K, Sakurai Y, Kondoh O, Sakamoto H. Antitumor activity of the selective ALK inhibitor alectinib in models of intracranial metastases. Cancer Chemother Pharmacol. 2014;74:1023-1028.

    • Löscher W, Potschka H. Blood-brain barrier active efflux transporters: ATP-binding cassette gene family. NeuroRx. 2005;2:86-98.

      Löscher W, Potschka H. Blood-brain barrier active efflux transporters: ATP-binding cassette gene family. NeuroRx. 2005;2:86-98.

    • Schinkel AH, Jonker JW. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv Drug Deliv Rev. 2003;55:3-29.

      Schinkel AH, Jonker JW. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv Drug Deliv Rev. 2003;55:3-29.

    • Bartels AL. Blood-brain barrier p-glycoprotein function in neurodegenerative disease. Curr Pharm Des. 2011;17:2771-2777.

      Bartels AL. Blood-brain barrier p-glycoprotein function in neurodegenerative disease. Curr Pharm Des. 2011;17:2771-2777.

    • Camidge DR, Dziadziuszko R, Peters S, et al. Updated efficacy and safety data and impact of the EML4-ALK fusion variant on the efficacy of alectinib in untreated ALK-positive advanced non-small cell lung cancer in the global phase III ALEX study. J Thorac Oncol. 2019;14(7):1233-1243.

      Camidge DR, Dziadziuszko R, Peters S, et al. Updated efficacy and safety data and impact of the EML4-ALK fusion variant on the efficacy of alectinib in untreated ALK-positive advanced non-small cell lung cancer in the global phase III ALEX study. J Thorac Oncol. 2019;14(7):1233-1243.

    • Peters S, Camidge DR, Shaw AT, et al. Alectinib versus crizotinib in untreated ALK-positive non–small cell lung cancer. N Engl J Med. 2017;377(protocol):1-384.

      Peters S, Camidge DR, Shaw AT, et al. Alectinib versus crizotinib in untreated ALK-positive non–small cell lung cancer. N Engl J Med. 2017;377(protocol):1-384.

    • Gadgeel, S. Alectinib vs crizotinib in treatment-naïve ALK+ NSCLC: CNS efficacy results from the ALEX study. Oral presentation at: European Society for Medical Oncology Congress; September, 2017; Madrid, Spain.

      Gadgeel, S. Alectinib vs crizotinib in treatment-naïve ALK+ NSCLC: CNS efficacy results from the ALEX study. Oral presentation at: European Society for Medical Oncology Congress; September, 2017; Madrid, Spain.

    • Peters S, Camidge DR, Shaw AT, et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 2017;377(suppl):1-14.

      Peters S, Camidge DR, Shaw AT, et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 2017;377(suppl):1-14.

    • Camidge DR, Peters S, Mok T, et al. Updated efficacy and safety data from the global phase III ALEX study of alectinib (ALC) vs crizotinib (CZ) in untreated advanced ALK+ NSCLC. Abstract no. 9043. Presented at: 2018 American Society of Clinical Oncology Annual Meeting; June 1-5, 2018; Chicago, IL.

      Camidge DR, Peters S, Mok T, et al. Updated efficacy and safety data from the global phase III ALEX study of alectinib (ALC) vs crizotinib (CZ) in untreated advanced ALK+ NSCLC. Abstract no. 9043. Presented at: 2018 American Society of Clinical Oncology Annual Meeting; June 1-5, 2018; Chicago, IL.

    • Mok T, Camidge DR, Gadgeel SM, et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020;31(8):1056-1064.

      Mok T, Camidge DR, Gadgeel SM, et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020;31(8):1056-1064.