First-Line Adverse Reactions

Adverse Reactions

  • Median duration of exposure: ALECENSA® (alectinib) 17.9 months; crizotinib 10.7 months 8
  • Serious adverse reactions occurred in 28% of patients treated with ALECENSA; serious adverse reactions reported in ≥ 2% of patients treated with ALECENSA were pneumonia (4.6%) and renal impairment (3.9%) 1
  • Grade ≥3 adverse events were reported for 41% of patients in the ALECENSA arm 1

ADVERSE DRUG REACTIONS (>10% FOR ALL NCI CTCAE GRADES OR ≥2% FOR GRADES 3-4) IN PATIENTS TREATED WITH ALECENSA OR CRIZOTINIB 1

  ALECENSA
(n=152)

crizotinib
(n=151)

Adverse Reaction
All Grades
Grades 3-4
All Grades
Grades 3-4
Gastrointestinal
Constipation
34% 0% 33% 0%
Nausea
14% 0.7% 48% 3.3%
Diarrhea
12% 0% 45% 2.0%
Vomiting
7.0% 0% 38% 3.3%
General
Fatiguea
26% 1.3% 23% 0.7%
Edemab
22% 0.7% 34% 0.7%
Musculoskeletal
Myalgiac
23% 0% 4.0% 0%
Skin
Rashd
15% 0.7% 13% 0%
Nervous system
Dysgeusiae
3.3% 0.7% 19% 0%
Eye
Vision disordersf
4.6% 0% 23% 0%
Cardiac
Bradycardiag
11% 0% 15% 0%
Renal
Renal impairmenth
12% 3.9%i 0% 0%
a Includes fatigue and asthenia.‬‬
b Includes peripheral edema, edema, eyelid edema, localized edema, and face edema.‬
c Includes myalgia and musculoskeletal pain.‬‬
d Includes rash, rash maculopapular, dermatitis acneiform, erythema, generalized rash, rash macular, rash papular, exfoliative rash, and pruritic rash.
e Includes dysgeusia and hypogeusia.
f Includes blurred vision, visual impairment, vitreous floaters, reduced visual acuity, and diplopia.
g Includes reported cases of bradycardia and sinus bradycardia but is not based on serial ECG assessment.‬‬
h Includes increased blood creatinine, creatinine renal clearance decreased, glomerular filtration rate decreased, and acute kidney injury.
i Includes two Grade 5 events.‬‬

TREATMENT-EMERGENT WORSENING IN LABORATORY VALUES OCCURRING IN >10% OF PATIENTS TREATED WITH ALECENSA OR CRIZOTINIB 1j

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%
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%

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

j Patients 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.

Discontinuations with ALECENSA 1

  • Permanent treatment discontinuation occurred in 11% of patients
    • Renal impairment (2.0%), hyperbilirubinemia (1.3%), increased ALT (1.3%), and increased AST (1.3%) were the most frequent adverse reactions leading to discontinuation

Dose modifications with ALECENSA 1

  • Dose reductions and drug interruption due to adverse reactions occurred in 16% and 19% of patients, respectively
    • Hyperbilirubinemia (6.0%), increased AST (5.0%), increased ALT (4.6%), and pneumonia (3.3%) were the most frequent adverse reactions leading to dose modifications

ALT=alanine transaminase; AST=aspartate transaminase; CPK=creatine phosphokinase; ECG=electrocardiogram; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events.

FIRST-LINE CLINICAL TRIAL

View the first-line ALEX clinical trial information for ALECENSA.

View First-Line Trial Design

FIRST-LINE EFFICACY

View the first-line efficacy data for ALECENSA.

View First-Line Data

FINANCIAL AND PRACTICE RESOURCES

Learn more about ALECENSA patient and practice resources.

Learn More

Important Safety Information & Indication

Indication

ALECENSA is indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.

Warnings and Precautions

Hepatotoxicity

  • Elevations of AST >5X the upper limit of normal (ULN) occurred in 4.6% of patients, and elevations of ALT >5X the ULN occurred in 5.3% of patients. Elevations of bilirubin >3X the ULN occurred in 3.7% of patients. The majority (69% of the patients with hepatic transaminase elevations and 68% of the patients with bilirubin elevations) of these events occurred during the first 3 months of treatment. Six patients discontinued ALECENSA for Grades 3-4 AST and/or ALT elevations, and 4 patients discontinued ALECENSA for Grade 3 bilirubin elevations. Concurrent elevations in ALT or AST ≥3X the ULN and total bilirubin ≥2X the ULN, with normal alkaline phosphatase, occurred in <1% of patients treated with ALECENSA across clinical trials. Three patients with Grades 3-4 AST/ALT elevations had drug-induced liver injury (2 documented by liver biopsy)
  • 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 3 (0.7%) patients treated with ALECENSA. One (0.2%) of these events was severe (Grade 3)
  • 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 8% of patients. The incidence of Grade ≥3 renal impairment was 1.7%, of which 0.5% were fatal events
  • Dose modifications for renal impairment were required in 3.2% of patients. Median time to Grade ≥3 renal impairment was 3.7 months (range 0.5 to 14.7 months)
  • Permanently discontinue ALECENSA for Grade 4 renal toxicity. Withhold ALECENSA for Grade 3 renal toxicity until recovery to ≤1.5X ULN, then resume at reduced dose

Bradycardia

  • Symptomatic bradycardia can occur with ALECENSA. Cases of bradycardia (8.6%) have been reported in patients treated with ALECENSA. Eighteen percent of 365 patients treated with ALECENSA for whom serial ECGs were available had heart rates of <50 beats per minute (bpm)
  • Monitor heart rate and blood pressure regularly. Dose modification is not required in cases of asymptomatic bradycardia. In cases of symptomatic bradycardia that are not life-threatening, withhold ALECENSA until recovery to asymptomatic bradycardia or to a heart rate of ≥60 bpm and evaluate concomitant medications known to cause bradycardia, as well as anti-hypertensive medications. If 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 case of recurrence. Permanently discontinue ALECENSA in cases of life-threatening bradycardia if no contributing concomitant medication is identified

Severe Myalgia and Creatine Phosphokinase (CPK) Elevation

  • Myalgia or musculoskeletal pain occurred in 26% of patients. The incidence of Grade 3 myalgia/musculoskeletal pain was 0.7%. Dose modifications for myalgia/musculoskeletal pain were required in 0.5% of patients
  • Elevations of CPK occurred in 41% of 347 patients with CPK laboratory data. The incidence of Grade 3 elevations of CPK was 4.0%. Median time to Grade 3 CPK elevation was 14 days (interquartile range 13-28 days). Dose modifications for elevation of CPK occurred in 3.2% of patients
  • 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

Embryo-Fetal Toxicity

  • Based on findings from animal studies and its mechanism of action, ALECENSA can cause fetal harm when administered to pregnant women. Administration of ALECENSA to pregnant rats and rabbits during the period of organogenesis resulted in embryo-fetal toxicity and abortion at maternally toxic doses with exposures approximately 2.7X those observed in humans with ALECENSA 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 1 week following the final dose

Most Common Adverse Reactions

  • The most common adverse reactions (incidence ≥20%) were constipation (34%), fatigue (26%), edema (22%), myalgia (23%), and anemia (20%)
  • Management of adverse reactions may require temporary interruption, dose reduction, or discontinuation of treatment with ALECENSA

Use in Specific Populations

Pregnancy

  • Based on animal studies and its mechanism of action, ALECENSA can cause fetal harm when administered to a pregnant woman. There are no available data on ALECENSA use in pregnant women
  • In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively

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 final dose

Females and Males of Reproductive Potential

  • ALECENSA can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ALECENSA and for 1 week after the final dose
  • Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with ALECENSA and for 3 months following the final dose

Patient Counseling Information

Photosensitivity

  • Inform patients of the signs and symptoms of photosensitivity. Advise patients to avoid prolonged sun exposure while taking ALECENSA and for at least 7 days after discontinuation and to use proper protection from the sun. Advise patients to use a broad spectrum ultraviolet A (UVA)/ultraviolet B (UVB) sunscreen and lip balm (SPF ≥50) to help protect against potential sunburn

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.