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ALECENSA: ALK+ treatment with a well-established safety profile

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Adverse reactions
Laboratory abnormalities
Real-world results

Primary analysis

Adverse drug reactions (>10% for all NCI CTCAE Grades or ≥2% for Grades 3-4) in patients treated with ALECENSA in ALEX1

Adverse reaction

 ALECENSA (n=152) crizotinib (n=151)
All Grades Grades 3-4 All Grades Grades 3-4

Constipation

 34% 0% 33% 0%

Fatiguea

 26% 1.3% 23% 0.7%

Myalgiab

 23% 1.3% 4% 0%

Edemac

 22% 0.7% 34% 0.7%

Rashd

 15% 0.7% 13% 0%

Nausea

 14% 0.7% 48% 3.3%

Renal Impairmente

 12% 3.9%g 0% 0%

Diarrhea

 12% 0% 45% 2%

Bradycardiaf

 11% 0% 15% 0%

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.

  • Safety results at 5 years post-hoc analysis were consistent with the originally reported adverse reactions of ALECENSA in ALEX3
    • Constipation (38.2%), anemia (27.6%), fatigue (22.4%), and increased blood bilirubin (22.4%) were the most common adverse events (≥20%) at 5 years of follow-up2
    • No new safety signals observed after up to 5 years of follow-up22

Laboratory abnormalities

Laboratory abnormalities occurring in >10% of patients treated with ALECENSA or crizotinib1h

Parameter ALECENSA (n=152) crizotinib (n=151)
All Grades Grades 3-4 All Grades Grades 3-4
Chemistry
Hyperbilirubinemia 54% 5% 4.7% 0%
Increased AST 50% 6% 56% 11%
Increased alkaline phosphatase 50% 0% 44% 0%
Increased ALT 40% 6% 62% 16%

The most common lab abnormalities occurred early
Incidence of hyperbilirubinemia was higher in the ALECENSA treatment arm. However, median time to onset for elevated AST, ALT, and bilirubin levels were comparable between treatment arms and the majority of events occurred within the first 1 to 2 months1,2
Increased creatinine 38% 4.1% 23% 0.7%
Increased CPK 37% 2.8% 52% 1.4%
Hypocalcemia 29% 0% 61% 1.4%
Hyperglycemia 22% 2.2% 19% 2.3%
Hyponatremia 18% 6% 20% 4.1%
Hypokalemia 17% 2% 12% 0.7%
Hypoalbuminemia 14% 0% 57% 3.4%
Hyperkalemia 12% 1.4% 16% 1.4%
Hypophosphatemia 9% 1.4% 25% 2.7%
Increased gamma glutamyl transferase 7% 0.7% 39% 4.1%
Hematology
Anemia 62% 7% 36% 0.7%
Lymphopenia 14% 1.4% 34% 4.1%
Neutropenia 14% 0% 36% 7%

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

hPatients 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.

Consistent safety profile across clinical and real-world experience23

Safety profile and dose modifications in the ALEX trial1,5

Parameter ALECENSA (n=152) crizotinib (n=151)
Median duration of exposure 17.9 months

(range: 0-29.0 months)		 10.7 months

(range: 0-27.0 months)
Grade 5 ARs 3%i 5%j
Grade ≥3 ARs 41% 50%
Dose modifications due to ARs
Dose reductions 16% 21%
Dose interruptions 19% 25%
Permanent discontinuations 11% 13%

iAll unrelated to treatment.5

jTwo related to treatment.5

Most frequent ARs (≥2%) leading to a dose modification for ALECENSA1,2 

  • Dose reduction: elevated AST (3.3%), elevated ALT (2%), elevated bilirubin (2%), anemia (2%), and hyperbilirubinemia (2%) 
  • Dose interruption: ALT increased (2.6%), pneumonia (2.6%), and AST increased (2%)  
  • Permanent discontinuation: renal impairment (2%) 

Real-world results23

  • In a real-world study, rates of dose modifications and discontinuations due to ARs for ALECENSA were comparable to the ALEX clinical trialk
    • The most common mAEs were rash (10%) and bradycardia (7.1%) in patients receiving ALECENSA 
    • Rates of dose adjustments with ALECENSA were 27.1%, interruptions were 22.9%, and treatment discontinuation was 2.9% 
    • The most common AEs contributing to dose adjustments were bradycardia (20.1%), rash (15.8%), and fatigue (15.8%) 

kA retrospective cohort study using electronic health record data in 117 adult patients with ALK-positive advanced NSCLC receiving ALK TKIs, with ALECENSA (n=70) or crizotinib (n=47) as the initial ALK TKI therapy.

ALK=anaplastic lymphoma kinase; ALT=alanine transaminase; AR=adverse reaction; AST=aspartate transaminase; CPK=creatinine phosphokinase; ECG=electrocardiogram; mAE=major adverse event; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events; TKI=tyrosine kinase inhibitor.

For more information

Go to dosing information
View ISI for ALECENSA

Indications & Important Safety Information

Indications

ALECENSA is a kinase inhibitor indicated for:

  • treatment of adult patients with ALK-positive metastatic NSCLC as detected by an FDA-approved test
  • 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

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.

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

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

    • Data on file. Genentech, Inc.

      Data on file. Genentech, Inc.

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      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. doi:10.1016/j.annonc.2020.04.478

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.4.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed May 29, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN 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 Guidelines® for detailed recommendations.

      Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.4.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed May 29, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN 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 Guidelines® for detailed recommendations.

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