Alecensa Drug Information

Generic name: ALECTINIB HYDROCHLORIDE

Save on Alecensa at your pharmacy Compare prices near you and start saving today—no enrollment required.

Uses of Alecensa

Adjuvant Treatment of Resected ALK-Positive Non-Small Cell Lung Cancer (NSCLC) ALECENSA is indicated as 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 Metastatic ALK-Positive NSCLC ALECENSA is indicated for the treatment of adult patients with ALK-positive metastatic NSCLC as detected by an FDA-approved test.

Dosage & Administration of Alecensa

Patient Selection

Select patients with resectable tumors for the adjuvant treatment of NSCLC with ALECENSA based on the presence of ALK positivity in tumor tissue. Select patients for the treatment of metastatic NSCLC with ALECENSA based on the presence of ALK positivity in tumor tissue or plasma specimens. If ALK rearrangements are not detected in a plasma specimen, test tumor tissue if feasible.

Information on FDA-approved tests for the detection of ALK rearrangements in NSCLC is available at http://www.fda.gov/CompanionDiagnostics.

Dosing and Administration

The recommended dosage information for ALECENSA is provided in Table 1. Table 1: ALECENSA Recommended Dosage and

Recommended Dosage for Hepatic Impairment

The recommended dose of ALECENSA in patients with severe hepatic impairment (Child-Pugh C) is 450 mg orally twice daily.

Dose Modifications for Adverse Reactions

The dose reduction schedule for ALECENSA is provided in Table 2. Table 2: ALECENSA Discontinue if patients are unable to tolerate the 300 mg twice daily dose. Recommendations for dose modifications of ALECENSA in case of adverse reactions are provided in Table 3.

Table 3:

Table 1: ALECENSA Recommended Dosage and Duration of Treatment
Indication	Recommended Dosage of ALECENSA	Duration
Adjuvant treatment of resected NSCLC	600 mg orally twice daily with food [see Clinical Pharmacology (12.3) ]	For a total of 2 years or until disease recurrence or unacceptable toxicity
Metastatic NSCLC		Until disease progression or unacceptable toxicity
Swallow capsules whole, do not open or dissolve the contents of the capsule. If a dose of ALECENSA is missed or vomiting occurs after taking a dose of ALECENSA, take the next dose at the scheduled time.

Table 2: ALECENSA Dose Reduction Schedule
Dose Reduction Schedule	Dose Level
Starting dose	600 mg taken orally twice daily
First dose reduction	450 mg taken orally twice daily
Second dose reduction	300 mg taken orally twice daily

Table 3: ALECENSA Dose Modifications for Adverse Reactions
Criteria ALT = alanine transaminase; AST = aspartate transaminase; ULN = upper limit of normal; ILD = interstitial lung disease; CPK = blood creatine phosphokinase	ALECENSA Dose Modification
ALT or AST elevation of greater than 5 times upper limit of normal (ULN) with total bilirubin less than or equal to 2 times ULN	Temporarily withhold until recovery to baseline or to less than or equal to 3 times ULN, then resume at reduced dose as per Table 2.
ALT or AST elevation greater than 3 times ULN with total bilirubin elevation greater than 2 times ULN in the absence of cholestasis or hemolysis	Permanently discontinue ALECENSA.
Total bilirubin elevation of greater than 3 times ULN	Temporarily withhold until recovery to baseline or to less than or equal to 1.5 times ULN, then resume at reduced dose as per Table 2.
Any grade treatment-related interstitial lung disease (ILD)/pneumonitis	Permanently discontinue ALECENSA.
Grade 3 renal impairment	Temporarily withhold until serum creatinine recovers to less than or equal to 1.5 times ULN, then resume at reduced dose.
Grade 4 renal impairment	Permanently discontinue ALECENSA.
Symptomatic bradycardia	Withhold ALECENSA until recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above. If contributing concomitant medication is identified and discontinued, or its dose is adjusted, resume ALECENSA at previous dose upon recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above. If no contributing concomitant medication is identified, or if contributing concomitant medications are not discontinued or dose modified, resume ALECENSA at reduced dose (see Table 2 ) upon recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above.
Bradycardia Heart rate less than 60 beats per minute (bpm) (life-threatening consequences, urgent intervention indicated)	Permanently discontinue ALECENSA if no contributing concomitant medication is identified. If contributing concomitant medication is identified and discontinued, or its dose is adjusted, resume ALECENSA at reduced dose (see Table 2 ) upon recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above, with frequent monitoring as clinically indicated. Permanently discontinue ALECENSA in case of recurrence.
CPK elevation greater than 5 times ULN	Temporarily withhold until recovery to baseline or to less than or equal to 2.5 times ULN, then resume at same dose.
CPK elevation greater than 10 times ULN or second occurrence of CPK elevation of greater than 5 times ULN	Temporarily withhold until recovery to baseline or to less than or equal to 2.5 times ULN, then resume at reduced dose as per Table 2.
Hemolytic Anemia	Withhold ALECENSA if hemolytic anemia is suspected. Upon resolution, resume at reduced dose or permanently discontinue.
Severe hypertriglyceridemia (blood triglycerides from 501 to 1,000 mg/dL or from 5.71 to 11.4 mmol/L) OR Life-threatening hypertriglyceridemia (blood triglycerides over 1,000 mg/dL or over 11.4 mmol/L)	Temporarily withhold until recovery to at least moderate hypertriglyceridemia (i.e., until blood triglycerides are ≤ 500 mg/dL or ≤ 5.7 mmol/L). Evaluate risk factors for pancreatitis and address those that are treatable before resuming treatment with ALECENSA. If an acute episode of pancreatitis occurs, temporarily withhold until full recovery before resuming treatment with ALECENSA. Resume ALECENSA at the same dose, with regular monitoring of blood triglyceride levels. If hypertriglyceridemia reoccurs, consider dose reduction of ALECENSA.

Side Effects of Alecensa

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population described in the WARNINGS AND PRECAUTIONS reflects exposure to ALECENSA as a single agent at 600 mg orally twice daily in 5 % were exposed for 6 months or longer and 64% were exposed for greater than one year. Adjuvant Treatment of Resected ALK-Positive NSCLC The safety of ALECENSA was evaluated in ALINA, a multi-center, open-label, randomized trial for the adjuvant treatment of patients with resected ALK-positive NSCLC.

At the time of DFS analysis, the median duration of exposure was 23.9 months for ALECENSA and 2.1 months for platinum-based chemotherapy. Permanent discontinuation of ALECENSA due to an adverse event occurred in 5% of patients; the most frequent adverse reactions (≥ 1%) that led to treatment discontinuation were pneumonitis and hepatotoxicity. Dosage interruptions of ALECENSA due to an adverse reaction occurred in 27% of patients.

Adverse reactions which required dosage interruption in ≥ 2% of patients included hepatotoxicity, increased blood CPK, COVID-19, myalgia, abdominal pain, and pneumonia. Dose reductions of ALECENSA due to an adverse reaction occurred in 26% of patients. Adverse reactions which required dose reductions in ≥ 2% of patients included hepatotoxicity, increased blood CPK, rash, bradycardia and myalgia.

Table 4 and 5 summarize the common adverse reactions and laboratory abnormalities observed in ALINA. Table 5: Worsening in Laboratory Values from Baseline Occurring in ≥ 20% of Patients Treated with ALECENSA in ALINA Previously Untreated Metastatic ALK-Positive NSCLC The safety of ALECENSA was evaluated in 152 patients with ALK-positive NSCLC in the ALEX study. The median duration of exposure to ALECENSA was 17.9 months.

Grade ≥ 3 adverse events were reported for 41% of patients in the ALECENSA arm. Fatal adverse reactions occurred in 3.3% of patients treated with ALECENSA; these were renal impairment (2 patients), sudden death, cardiac arrest, and pneumonia (1 patient each). Permanent discontinuation of ALECENSA for adverse reactions occurred in 11% of patients.

Adverse reactions which required dose reductions in > 2% of patients included hyperbilirubinemia, increased AST and increased ALT. Tables 6 and 7 summarize the common adverse reactions and laboratory abnormalities observed in ALEX. Table 7: Worsening in Laboratory Values Occurring in > 7 Metastatic ALK-Positive NSCLC Previously Treated with Crizotinib The safety of ALECENSA was evaluated in 253 patients with ALK-positive non-small cell lung cancer (NSCLC) treated with ALECENSA in two clinical trials, Studies NP28761 and NP28673.

Serious adverse reactions occurred in 19% of patients; the most frequently reported serious adverse reactions were pulmonary embolism ( %). The most frequent adverse reactions that led to permanent discontinuation were hyperbilirubinemia (1.6%), increased ALT levels (1.6%), and increased AST levels (1.2%). Overall, 23% of patients initiating treatment at the recommended dose required at least one dose reduction.

The median time to first dose reduction was 48 days. The most frequent adverse reactions that led to dose reductions or interruptions were elevations in bilirubin and vomiting (2.8%). Tables 8 and 9 summarize the common adverse reactions and laboratory abnormalities observed in Studies NP28761 and NP28673.

Patients were advised to avoid sun exposure and to use broad-spectrum sunscreen. The incidence of Grade 2 photosensitivity was 0.4%; the remaining events were Grade 1 in severity. Table 9: Treatment-Emergent Worsening in Laboratory Values Occurring in >

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of ALECENSA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Metabolism and nutrition disorders: hypertriglyceridemia leading to pancreatitis

Table 7: Worsening in Laboratory Values Occurring in > 10% of Patients in ALEX
Parameter	ALECENSA N=152		Crizotinib N=151
	All Grades (%)	Grades 3–4 (%)	All Grades (%)	Grades 3–4 (%)
Note: Based on National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. Excludes patients with no post-baseline lab assessments.
Chemistry
Hyperbilirubinemia n=147 for alectinib (with baseline values missing for 1 of these patients), n=148 for crizotinib.	54	5	4.7	0
Increased AST n=147 for alectinib (with baseline values missing for 2 of these patients), n=148 for crizotinib.	50	6	56	11
Increased alkaline phosphatase n=147 for alectinib, n=148 for crizotinib.	50	0	44	0
Increased ALT	40	6	62	16
Increased creatinine, Only patients with creatinine increases based on ULN definition.	38	4.1	23	0.7
Increased CPK n=143 for alectinib (with baseline values missing for 14 of these patients), n=143 for crizotinib (with baseline values missing for 13 of these patients).	37	2.8	52	1.4
Hypocalcemia	29	0	61	1.4
Hyperglycemia n=134 for alectinib (with baseline values missing for 18 of these patients), n=131 for crizotinib (with baseline values missing for 8 of these patients).	22	2.2	19	2.3
Hyponatremia n=147 for alectinib, n=148 for crizotinib (with baseline values missing for 1 of these patients).	18	6	20	4.1
Hypokalemia	17	2	12	0.7
Hypoalbuminemia n=146 for alectinib (with baseline values missing for 1 of these patients), n=148 for crizotinib (with baseline values missing for 1 of these patients).	14	0	57	3.4
Hyperkalemia	12	1.4	16	1.4
Hypophosphatemia n=145 for alectinib (with baseline values missing for 2 of these patients), n=148 for crizotinib (with baseline values missing for 4 of these patients).	9	1.4	25	2.7
Increased gamma glutamyl transferase n=143 for alectinib (with baseline values missing for 4 of these patients), n=148 (with baseline values missing for 5 of these patients).	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

Table 8: Adverse Reactions in ≥ 10% (All Grades) or ≥ 2% (Grades 3–4) of Patients in Studies NP28761 and NP28673
Adverse Reactions	ALECENSA N=253
Adverse Reactions	All Grades (%)	Grades 3–4 (%) Per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Fatigue Includes fatigue and asthenia.	41	1.2
Constipation	34	0
Edema Includes peripheral edema, edema, generalized edema, eyelid edema, and periorbital edema.	30	0.8
Myalgia Includes myalgia and musculoskeletal pain.	29	1.2
Cough	19	0
Rash Includes rash, maculopapular rash, acneiform dermatitis, erythema, generalized rash, papular rash, pruritic rash, and macular rash.	18	0.4
Nausea	18	0
Headache	17	0.8
Diarrhea	16	1.2
Dyspnea	16	3.6 Includes one Grade 5 event.
Back pain	12	0
Vomiting	12	0.4
Increased weight	11	0.4
Vision disorder Includes blurred vision, vitreous floaters, visual impairment, reduced visual acuity, asthenopia, and diplopia.	10	0

Table 9: Treatment-Emergent Worsening in Laboratory Values Occurring in > 20% of Patients in Studies NP28761 and NP28673
Parameter	ALECENSA N=250
Parameter	All Grades (%)	Grades 3–4 (%) Per CTCAE version 4.0
Chemistry
Increased blood triglycerides n=98 for blood triglycerides (with baseline values missing for 0 of these patients); data available from Study NP28761.	57	7
Increased AST	51	3.6
Increased Alkaline Phosphatase	47	1.2
Increased CPK n=218 for CPK (with baseline values missing for 91 of these patients).	43	4.6
Hyperbilirubinemia	39	2.4
Hyperglycemia n=152 for fasting blood glucose (with baseline values missing for 5 of these patients).	36	2.0
Increased ALT	34	4.8
Hypocalcemia	32	0.4
Hypokalemia	29	4.0
Increased Creatinine Only patients with creatinine increases based on ULN definition.	28	0
Hypophosphatemia	21	2.8
Hyponatremia	20	2.0
Hematology
Anemia	56	2.0
Lymphopenia n=217 for lymphocytes (with baseline values missing for 5 of these patients).	22	4.6

Warnings & Cautions for Alecensa

Hepatotoxicity

Severe hepatotoxicity, including drug-induced liver injury, occurred in patients treated with ALECENSA. In the pooled safety population of patients who received ALECENSA, hepatotoxicity occurred in 41% of patients 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. In the pooled safety population, concurrent elevations in ALT or 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 two 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 as described in Table 3.

Interstitial Lung Disease (ILD)/Pneumonitis

ILD/pneumonitis occurred in patients treated with ALECENSA. Five patients (0.9%) in the pooled safety population discontinued ALECENSA due to ILD/pneumonitis. Promptly investigate for ILD/pneumonitis in any patient who presents with worsening of respiratory symptoms indicative of ILD/pneumonitis (e.g., 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, including fatal cases, occurred in patients treated with ALECENSA. 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. In the pooled safety population, bradycardia occurred in 11% of patients treated with ALECENSA. Twenty percent of 521 patients treated with ALECENSA, 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 (see Table 2 ) 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. Permanently discontinue ALECENSA 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. In the pooled safety population, myalgia (including muscle- and musculoskeletal-related reactions) occurred in 31% of patients treated with ALECENSA, including Grade ≥ 3 in 0.8% of patients. Dosage modifications for myalgia events were required in 2.1% of patients.

Dosage modifications for elevation of CPK occurred in 5% 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.

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.

Severe Hypertriglyceridemia Leading to Pancreatitis

Hypertriglyceridemia, including severe cases associated with life-threatening acute pancreatitis, has been reported in patients treated with ALECENSA in the postmarketing setting. Dose modifications due to hypertriglyceridemia occurred in 0.9% of patients, and permanent discontinuation occurred in 0.2% of patients. Monitor blood triglycerides before initiation and periodically during treatment with ALECENSA.

In patients with triglyceride levels ≥ 500 mg/dL, withhold ALECENSA and monitor for signs and symptoms of pancreatitis and monitor lipase and amylase periodically until triglyceride levels recover to blood triglycerides ≤ 500 mg/dL or ≤ 5.7 mmol/L. If an acute episode of pancreatitis occurs, temporarily withhold ALECENSA until full recovery. Withhold, then resume at the same or reduced dose or permanently discontinue ALECENSA based on severity.

Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, ALECENSA can cause fetal harm when administered to pregnant women. Oral 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 and females of reproductive potential 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.

Pregnancy Safety for Alecensa

Pregnancy Risk Summary Based on findings from 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. Administration of alectinib to pregnant rats and rabbits by oral gavage 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 treated with alectinib at 600 mg twice daily (see Data ).

Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively. Data Animal Data In a preliminary rabbit embryo-fetal study, administration of alectinib by oral gavage during the period of organogenesis resulted in abortion or complete embryo-fetal mortality at a maternally toxic dose of 27 mg/kg/day (approximately 2.9-fold the estimated area under the curve (AUC 0-24h,ss ) in humans treated with alectinib 600 mg twice daily) in three of six pregnant rabbits.

The remaining three pregnant rabbits in this group had few live fetuses, decreased fetal and placental weights, and retroesophageal subclavian artery. In a rat preliminary embryo-fetal development study, administration of alectinib during organogenesis resulted in complete litter loss in all pregnant rats at 27 mg/kg/day (approximately 4.5-fold the estimated AUC 0-24h,ss in humans treated with alectinib 600 mg twice daily). Doses greater than or equal to 9 mg/kg/day (approximately 2.7-fold the estimated human AUC 0-24h,ss in humans treated with alectinib 600 mg twice daily), resulted in maternal toxicity as well as developmental toxicities including decreased fetal weight, dilated ureter, thymic cord, small ventricle and thin ventricle wall, and reduced number of sacral and caudal vertebrae.

Pediatric Use of Alecensa

Pediatric Use The safety and effectiveness of ALECENSA in pediatric patients have not been established. Animal Data Juvenile animal studies have not been conducted using alectinib. In general toxicology studies, treatment of rats with doses of alectinib resulting in exposures greater than or equal to approximately 4.5-fold those in humans treated with alectinib at 600 mg twice daily resulted in changes in the growing teeth and bones.

Findings in teeth included discoloration and changes in tooth size along with histopathological disarrangement of the ameloblast and odontoblast layers. There were also decreases in the trabecular bone and increased osteoclast activity in the femur and sternum.

Overdosage Information for Alecensa

No experience with overdose is available. There is no specific antidote for overdose with ALECENSA. Alectinib and its major active metabolite M4 are > 99% bound to plasma proteins; therefore, hemodialysis is likely to be ineffective in the treatment of overdose.

Clinical Studies of Alecensa

Adjuvant Treatment of Resected ALK-Positive NSCLC

The efficacy of ALECENSA for the adjuvant treatment of patients with ALK-positive NSCLC following complete tumor resection was evaluated in a global, randomized open-label clinical trial (ALINA: NCT03456076). Eligible patients were required to have resectable ALK-positive NSCLC, Stage IB (tumors ≥ 4 cm) – IIIA per the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) Staging System, 7 th Edition. ALK rearrangements were identified by a locally performed FDA-approved ALK test or by a centrally performed VENTANA ALK (D5F3) CDx assay.

Randomization was stratified by race (Asian vs. other races) and stage of disease (IB vs. II vs. IIIA).

Patients were randomized (1:1) to receive ALECENSA 600 mg orally twice daily or platinum-based chemotherapy following tumor resection. Treatment with ALECENSA continued for a total of 2 years, or until disease recurrence or unacceptable toxicity. The major efficacy outcome measures were disease-free survival (DFS) in patients with stage II-IIIA NSCLC and DFS in patients with stage IB-IIIA NSCLC (intent-to-treat population) as assessed by investigator.

DFS was defined as the time from date of randomization to the date of occurrence of any of the following: first documented recurrence of disease, new primary NSCLC, or death due to any cause, whichever occurred first. An additional efficacy outcome measure was overall survival (OS) in the ITT population. A total of 257 patients were randomized to ALECENSA (N=130) or to chemotherapy (N=127).

ALINA demonstrated a statistically significant improvement in DFS for patients treated with ALECENSA compared to patients treated with chemotherapy. OS data were not mature at the time of DFS analysis with 2.3% of deaths reported in the ITT population. The efficacy results from ALINA are summarized in Table 10 and Figure 1.

Table 10: Investigator-Assessed DFS Results in ALINA Figure 1: Kaplan-Meier Curves of Investigator-Assessed DFS (ITT Population) in ALINA In an exploratory analysis of site(s) of relapse, the proportion of patients with brain involvement at the time of disease recurrence was 4 patients (3.1%) in the ALECENSA arm and 14 patients (11%) in the chemotherapy arm. Figure 1

Treatment of Metastatic ALK-Positive NSCLC Previously Untreated Metastatic ALK-Positive NSCLC The efficacy of ALECENSA for the treatment of patients with ALK-positive NSCLC who had not received prior systemic therapy for metastatic disease was established in an open-label, randomized, active-controlled, multicenter study (ALEX: NCT02075840). Patients were required to have an ECOG performance status of 0-2 and ALK-positive NSCLC as identified by the VENTANA ALK (D5F3) CDx assay. Neurologically stable patients with treated or untreated central nervous system (CNS) metastases, including leptomeningeal metastases, were eligible; patients with neurologic signs and symptoms due to CNS metastases were required to have completed whole brain radiation or gamma knife irradiation at least 14 days prior to enrollment and be clinically stable.

Patients with a baseline QTc > 470 ms were ineligible. Patients were randomized 1:1 to receive ALECENSA 600 mg orally twice daily or crizotinib 250 mg orally twice daily. Randomization was stratified by ECOG performance status (0/1 vs. 2), race (Asian vs. other races), and the presence or absence of CNS metastases at baseline.

Treatment on both arms was continued until disease progression or unacceptable toxicity. The major efficacy outcome measure was progression-free survival (PFS) as determined by investigator assessment (INV) according to RECIST v1.1. Additional efficacy outcome measures were PFS as determined by independent review committee (IRC), time to CNS progression by IRC based on RECIST v1.1, overall response rate (ORR) and duration of response (DOR), and OS.

Additional exploratory outcome measures were CNS objective response rate (CNS-ORR) and CNS duration of response (CNS-DOR) by IRC in patients with CNS metastases at baseline. A total of 303 patients were randomized to ALECENSA (n=152) or crizotinib (n=151). The majority of patients had adenocarcinoma (92%) and never smoked (63%).

CNS metastases were present in 40% (n=122) of patients: of these, 43 patients had measurable CNS lesions as determined by an IRC. The ALEX study demonstrated a significant improvement in PFS. The time to cause-specific CNS progression as assessed by IRC was also significantly improved; there was a lower incidence of progression in the CNS as the first site of disease progression, alone or with concurrent systemic progression, in the ALECENSA arm (12%) as compared to the crizotinib arm (45%).

Efficacy results from ALEX are summarized in Table (IRC) in ALEX PFS results as determined by investigator assessment (HR=0.48, stratified log-rank p<0.0001) were similar to those estimated by IRC. While OS was not formally tested due to the prespecified hierarchical testing strategy, there was no evidence of a detrimental effect on OS at the time of the final analysis; the OS HR was The results of prespecified exploratory analyses of CNS response rate in patients with measurable CNS lesions at baseline are summarized in Table 12. Table 12: IRC-Assessed CNS Responses in Patients with Measurable CNS Lesions at Baseline in ALEX Figure 2 Metastatic ALK-Positive NSCLC Previously Treated with Crizotinib The safety and efficacy of ALECENSA were established in two single-arm, multicenter clinical trials: NP28761 (NCT01588028) and NP28673 (NCT01801111).

Patients with locally advanced or metastatic ALK-positive NSCLC, who have progressed on crizotinib, with documented ALK-positive NSCLC based on an FDA-approved test, and ECOG PS of 0-2 were enrolled in both studies. Eligibility criteria permitted enrollment of patients with prior chemotherapy and prior CNS radiotherapy provided that CNS metastases were stable for at least two weeks. All patients received ALECENSA 600 mg orally twice daily.

The major efficacy outcome measure in both studies was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as evaluated per Independent Review Committee (IRC). Additional outcome measures as evaluated by the IRC included duration of response (DOR), CNS ORR, and CNS DOR. NP28761 was conducted in North America and enrolled 87 patients.

NP28673 was conducted internationally and enrolled 138 patients. Efficacy results from NP28761 and NP28673 in all treated patients are summarized in Table 13. The median duration of follow-up on Study NP28761 was 4.8 months for both IRC and Investigator assessments and on Study NP28673, 10.9 months for IRC assessment and 7.0 months for Investigator assessment.

All responses were partial responses. Table 13: Efficacy Results in Studies NP287 7.8 An assessment of ORR and duration of response for CNS metastases in the subgroup of 51 patients in NP28761 and NP28673 with baseline measurable lesions in the CNS according to RECIST v1.1 are summarized in Table 14. Responses were observed irrespective of prior brain radiation status.

Table 11: Efficacy Results in ALEX per IRC Assessment
	ALECENSA N=152	Crizotinib N=151
CNS: central nervous system, ORR: overall response rate, IRC: independent review committee, CI: confidence interval, NE: not estimable.
Progression-Free Survival
Number of events (%)	63 (41%)	92 (61%)
Progressive disease (%)	51 (34%)	82 (54%)
Death (%)	12 (8%)	10 (7%)
Median in months (95% CI)	25.7 (19.9, NE)	10.4 (7.7, 14.6)
Hazard ratio (95% CI) Stratified by race (Asian vs. other races) and CNS metastases at baseline (yes vs. no) for Cox model, log-rank test and Cochran Mantel-Haenszel test, respectively	0.53 (0.38, 0.73)
P-value	< 0.0001
Overall Response Rate
Overall response rate, % (95% CI) Clopper and Pearson exact binomial 95% confidence interval.	79% (72, 85)	72% (64, 79)
P-value	0.1652
Complete response, %	13%	6%
Partial response, %	66%	66%

Table 12: IRC-Assessed CNS Responses in Patients with Measurable CNS Lesions at Baseline in ALEX
	ALECENSA	Crizotinib
IRC: Independent Review Committee; CI: Confidence Interval; NE: Not Estimable
CNS Tumor Response Assessment	N = 21	N = 22
CNS Objective Response Rate, % (95% CI Clopper and Pearson exact binomial 95% confidence interval )	81% (58, 95)	50% (28,72)
Complete Response	38%	5%
Duration of CNS Response
Number of responders	17	11
CNS response duration ≥ 12 months	59%	36%

Table 13: Efficacy Results in Studies NP28761 and NP28673
Efficacy Parameter	NP28761 (N=87)		NP28673 (N=138)
Efficacy Parameter	IRC 18 patients in NP28761 and 16 patients in NP28673 did not have measurable disease at baseline as per IRC assessment and were classified as non-responders in the IRC analysis. Assessment	Investigator Assessment	IRC Assessment	Investigator Assessment
Objective Response Rate (95% CI)	38% (28; 49)	46% (35; 57)	44% (36; 53)	48% (39; 57)
Number of Responders	33	40	61	66
Duration of Response, median in months (95% CI)	7.5 (4.9, Not Estimable)	NE (4.9, Not Estimable)	11.2 (9.6, Not Estimable)	7.8 (7.4, 9.2)

Table 14: CNS Objective Response in Patients with Measurable CNS Lesions in Studies NP28761 and NP28673
Efficacy Parameter	N=51
CNS Objective Response Rate (95% CI)	61% (46, 74)
Complete Response	18%
Partial Response	43%
CNS Duration of Response, median in months (95% CI)	9.1 (5.8, Not Estimable)

Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.

Ready to save on Alecensa?

Compare prescription prices at over 70,000 pharmacies and start saving today—no enrollment required.

Compare Alecensa Prices