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| ALECENSA® (alectinib) is now FDA approved with a new indication for the first-line treatment of patients with ALK+ mNSCLC1 |
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The efficacy and safety of ALECENSA were established in the head-to-head, global, open-label, randomized Phase 3 ALEX trial of 303 first-line patients with ALK+ mNSCLC vs crizotinib. The primary efficacy endpoint was PFS as determined by Investigator and the secondary endpoint was PFS by IRC assessment, both according to RECIST v1.1.1,3 |
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| ALECENSA More Than Doubled mPFS vs Crizotinib |
| ALECENSA Reduced the Risk of Progression or Death by 47%1 |
| IRC-Assessed PFS1 |
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Patients with event: ALECENSA 41% (n=63); crizotinib 61% (n=92)1 |
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Investigator-assessed PFS: Results were similar to that observed by IRC1 |
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HR=0.48 (95% CI: 0.35, 0.66); P<0.0001 |
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| ALECENSA Significantly Delayed Progression in the CNS vs Crizotinib |
| Patients With and Without CNS Metastases Were Included in This Analysis1 |
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Time to CNS progression is an evaluation of the percentage of patients with tumors spreading to or growing in the CNS as the first site of progression (either as the sole site of progression or with concurrent systemic progression). This analysis does not include death as a progression event1,3,4 |
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| Time to Cause-Specific CNS Progression (Percentage of Patients With CNS as First Site of Progression)1 |
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Fewer patients progressed in the CNS when treated with ALECENSA (n=18/152, 12%) vs crizotinib (n=68/151, 45%)1 |
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Median duration of follow-up: ALECENSA 18.6 months; crizotinib 17.6 months3 |
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| Adverse Reactions |
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Median duration of exposure: ALECENSA 17.9 months; crizotinib 10.7 months3 |
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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 |
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Grade ≥3 adverse events were reported for 41% of patients in the ALECENSA arm1 |
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| Adverse Drug Reactions (>10% for All NCI CTCAE Grades or ≥2% for Grades 3-4) in Patients Treated With ALECENSA or Crizotinib1 |
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| Discover more about ALECENSA |
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| Indication |
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| 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. |
| Important Safety Information |
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| Warnings and Precautions |
| Hepatotoxicity |
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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 |
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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 |
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| Interstitial Lung Disease (ILD)/Pneumonitis |
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ILD/pneumonitis occurred in 3 (0.7%) patients treated with ALECENSA. One (0.2%) of these events was severe (Grade 3) |
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Promptly investigate for ILD/pneumonitis in any patient who presents with worsening of respiratory symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, and fever) |
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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 |
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| Renal Impairment |
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Renal impairment occurred in 8% of patients. The incidence of Grade ≥3 renal impairment was 1.7%, of which 0.5% were fatal events |
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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) |
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Permanently discontinue ALECENSA for Grade 4 renal toxicity. Withhold ALECENSA for Grade 3 renal toxicity, then resume at reduced dose |
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| Bradycardia |
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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) |
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Monitor heart rate and blood pressure regularly |
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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 |
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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 |
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Permanently discontinue ALECENSA in case of recurrence or in cases of life-threatening bradycardia if no contributing concomitant medication is identified |
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| Severe Myalgia and Creatine Phosphokinase (CPK) Elevation |
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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 |
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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 |
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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, then resume or dose reduce ALECENSA |
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| Embryo-Fetal Toxicity |
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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 |
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Advise females of reproductive potential to use effective contraception during treatment with ALECENSA and for 1 week following the final dose |
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Advise males with female partners of reproductive potential to use effective contraception during treatment with ALECENSA and for 3 months following the final dose |
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| Most Common Adverse Reactions |
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The most common adverse reactions (incidence ≥20%) were constipation (34%), fatigue (26%), edema (22%), myalgia (23%), and anemia (20%) |
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Management of adverse reactions may require temporary interruption, dose reduction, or discontinuation of treatment with ALECENSA |
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| Use in Specific Populations |
| Lactation Risk Summary |
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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 final dose |
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| 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. |
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