For Patients and Caregivers

Prescribing Information

ALECENSA® (alectinib) Significantly Reduced the Risk of CNS as the First Site of Progression

Primary Analysis

1L Clinical Trial: The primary efficacy endpoint in the ALEX trial was PFS by Investigator (HR=0.48 [95% CI: 0.35, 0.66]; P<0.0001). Additional efficacy endpoints were PFS, ORR, DOR, time to cause-specific CNS progression by IRC, and OS.2

  • ALECENSA achieved mPFS >2 years at primary analysis and ~3 years at exploratory follow-up analysis2,15a

aThe exploratory follow-up, conducted 10 months later, was assessed by investigators, and no formal treatment comparisons were performed.2,4,20

ALK+ mNSCLC has a propensity to metastasize to the brain3

  • The efficacy of ALECENSA was evaluated in delaying tumors from spreading to or growing in the CNS as the first site of progression alone or with concurrent systemic progression (time to cause-specific CNS progression)2-4,18
    • This analysis was conducted to separate the effect of ALECENSA on CNS progression from systemic
      progression or death
    • Patients who first progressed systemically, and patients with death prior to CNS or systemic progression (ALECENSA n=47; crizotinib n=42),a were not included as events

Percentage of Patients With CNS as the First Site of Progression (Including Those Who Had Concurrent Systemic Progression)2,4 | IRC

ALECENSA® (alectinib) vs Crizotinib Patients with CNS as the First Site of Progression

84% reduction in risk of tumors spreading to or growing in the CNS as the first site of progression (HR=0.16 [95% CI: 0.10, 0.28]); P<0.0001b

Safety Profile

Exploratory Subgroup Analysis of Patients With CNS as the First Site of Progression (Including Those Who Had Concurrent Systemic Progression)17 | IRC

ALECENSA® (alectinib) vs Crizotinib CNS Progression Regardless of CNS Metastases at Baseline

All exploratory analyses are descriptive in nature. Subgroups were not powered to show differences between treatment arms.16

aSystemic progression without prior CNS progression (ALECENSA n=36; crizotinib n=33); death prior to CNS or systemic progression (ALECENSA n=11; crizotinib n=9).4
bCause-specific HR and 95% CI were estimated by Cox model where patients with competing events (systemic progression and death prior to CNS or systemic progression) were censored at the time of these events. P-values were estimated from two-sided stratified cause-specific log-rank tests.18
cExcludes 1 patient in the ALECENSA arm with no CNS metastases by IRC who had received prior radiotherapy.17

ALECENSA Delivered Durable CNS Responses

Exploratory Analysis of CNS Responses in Patients With Measurable CNS Metastases at Baseline2 | IRC 

CNS Response Rates ALECENSA® (alectinib) vs Crizotinib in Patients With CNS Metastases
  • 59% of patients experienced a CNS response that lasted for a year or more with ALECENSA vs 36% of patients with crizotinib2

All exploratory analyses are descriptive in nature. Subgroups were not powered to show differences between treatment arms.16

1L=first-line; CI=confidence interval; CNS=central nervous system; CR=complete response; HR=hazard ratio; IRC=Independent Review Committee; ORR=objective response rate; PFS=progression-free survival.

Next: 1L Safety Profile
Alectinib (ALECENSA) NCCN Recommendation Category 1 Preferred

Alectinib (ALECENSA) is recommended by National Comprehensive Cancer Network® (NCCN®) as a first-line treatment option for ALK+ metastatic NSCLC (Category 1, Preferred)5ab

aWhen an ALK rearrangement is discovered prior to first-line systemic therapy.
bNCCN makes no warranties of any kind whatsoever regarding their content, use, or application, and disclaims any responsibility for their application or use in any way. See the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for detailed recommendations.

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1L PFS Results

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

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Dosing and Administration

Learn about dosing and monitoring for ALECENSA.

View ALECENSA Dosing
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Financial Support for Patients

Learn more about ALECENSA patient financial and practice resources.

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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.

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    • 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.

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    • 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.

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    • 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.

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