GILOTRIF: For the first step in the treatment of mNSCLC with Del 19

EXPLORE
THE BODY OF
EVIDENCE
GILOTRIF: For the first step
in the treatment of mNSCLC
with Del 19 and L858R
EGFR mutations
mNSCLC=metastatic non-small cell lung cancer;
FDA=US Food and Drug Administration.
INDICATIONS AND USAGE
GILOTRIF is indicated for the first-line treatment of patients with metastatic
non-small cell lung cancer (NSCLC) whose tumors have epidermal growth
factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution
mutations as detected by an FDA-approved test.
Limitation of Use: Safety and efficacy of GILOTRIF have not been
established in patients whose tumors have other EGFR mutations.
GILOTRIF is indicated for the treatment of patients with metastatic
squamous NSCLC progressing after platinum-based chemotherapy.
Please see Important Safety Information starting on page 2.
Click here for full Prescribing Information, including Patient Information.
THINK DEL 19. THINK GILOTRIF.
FOR THE 1ST-LINE TREATMENT OF EGFR M+ mNSCLC VS CHEMOTHERAPY
GILOTRIF: Only agent with proven overall survival
in patients with Del 19 mutations1-3
Median OS in LUX-Lung 3
Del 19 mutations populationa,b
100
Overall survival (%)
80
GILOTRIF
(40 mg orally once daily; n=112)
Pemetrexed/cisplatin
(500 mg/m2 / 75 mg/m2 every
3 weeks, up to 6 cycles; n=57)
33.3
HR: 0.55 (95% CI, 0.36-0.79)
months
60
45% reduction
in risk of death
40
21.1
months
20
0
0
3
6
9
12
15
18
21
24
27
30
33
36
39
42
45
48
51
Time of overall survival (months)
In a prespecified subgroup analysis of patients with Del 19 mutations for the secondary endpoint of OS.
Measured by an independent central radiology review.
a
b
OS=overall survival; HR=hazard ratio; CI=confidence interval; PFS=progression-free survival.
Primary endpoint: Median PFS for Del 19 mutations (n=170)1,4,5
13.7 MONTHS
GILOTRIF
Pemetrexed/
cisplatin
5.6 MONTHS
0
2
4
6
8
Time (months)
10
12
14
16
HR: 0.28 (95% CI, 0.18-0.44)
SELECTED IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Diarrhea
•GILOTRIF can cause diarrhea which may be severe and can result in dehydration with or without renal impairment.
In clinical studies, some of these cases were fatal.
•For patients who develop Grade 2 diarrhea lasting more than 48 hours or Grade 3 or greater diarrhea, withhold
GILOTRIF until diarrhea resolves to Grade 1 or less, and then resume at a reduced dose.
•Provide patients with an anti-diarrheal agent (e.g., loperamide) for
self-administration at the onset of diarrhea and instruct patients to
continue anti-diarrheal until loose stools cease for 12 hours.
Please see additional Important Safety Information continued on
following pages. Click here for full Prescribing Information, including
Patient Information.
THINK DEL 19. THINK GILOTRIF.
2
FOR THE 1ST-LINE TREATMENT OF mNSCLC WITH L858R EGFR MUTATIONS
GILOTRIF: Approved treatment option for patients with L858R1,2
Median OS in LUX-Lung 3
L858R mutation populationa,b
100
40.3
months
Overall survival (%)
80
60
40
GILOTRIF
(40 mg orally once daily; n=91)
Pemetrexed/cisplatin
(500 mg/m2 / 75 mg/m2 every
3 weeks, up to 6 cycles; n=47)
20
27.6
13.6
months
months
HR:1.30 (95% CI, 0.80-2.11)
0
0
3
6
9
12
15
18
21
24
27
30
33
36
39
42
45
48
51
Time of overall survival (months)
In a prespecified subgroup analysis of patients with L858R mutations for the secondary endpoint of OS.
Measured by an independent central radiology review.
a
b
Primary endpoint: Median PFS for L858R (exon 21) mutations (n=138)1,4,5
10.8 MONTHS
GILOTRIF
Pemetrexed/
cisplatin
8.1 MONTHS
0
2
4
6
8
Time (months)
10
12
14
16
HR: 0.73 (95% CI, 0.46-1.17)
SELECTED IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Bullous and Exfoliative Skin Disorders
•GILOTRIF can result in cutaneous reactions consisting of rash, erythema, and acneiform rash. In addition,
palmar-plantar erythrodysesthesia syndrome was observed in clinical trials in patients taking GILOTRIF.
•Discontinue GILOTRIF in patients who develop life-threatening bullous, blistering, or exfoliating
lesions. For patients who develop Grade 2 cutaneous adverse reactions lasting more than 7 days,
intolerable Grade 2, or Grade 3 cutaneous reactions, withhold GILOTRIF.
When the adverse reaction resolves to Grade 1 or less, resume
GILOTRIF with appropriate dose reduction.
Please see additional Important Safety Information continued on
following pages. Click here for full Prescribing Information, including
Patient Information.
THINK DEL 19. THINK GILOTRIF.
3
GILOTRIF: Established safety profile
Adverse reactions reported in LUX-Lung 3 in ≥10% of GILOTRIF-treated patients1
Adverse reaction
GILOTRIF (n=229)
Pemetrexed/cisplatin (n=111)
All grades, %
Grade 3a, %
All grades, %
Grade 3a, %
Gastrointestinal disorders
Diarrhea
Stomatitisb
Cheilitis
96
71
12
15
9
0
23
15
1
2
1
0
Skin and subcutaneous tissue disorders
Rash/acneiform dermatitisc
Pruritus
Dry skin
90
21
31
16
0
0
11
1
2
0
0
0
Infections
Paronychiad
Cystitis
58
13
11
1
0
5
0
0
Respiratory, thoracic, and mediastinal
disorders
Epistaxis
Rhinorrhea
17
11
0
0
2
6
1
0
Investigations
Weight decreased
17
1
14
1
General disorders and administration
site conditions
Pyrexia
12
0
6
0
Eye disorders
Conjunctivitis
11
0
3
0
Other clinically important adverse reactions observed in patients treated with GILOTRIF include: decreased
appetite (29%), nausea (25%), and vomiting (23%).1
None of the adverse reactions in this table except stomatitis (1 patient on GILOTRIF [0.4%]) were grade 4 in severity.
Includes stomatitis, aphthous stomatitis, mucosal inflammation, mouth ulceration, oral mucosa erosion, mucosal erosion,
mucosal ulceration.
c
Includes acne, acne pustular, dermatitis, acneiform dermatitis, dermatosis, drug eruption, erythema, exfoliative rash, folliculitis,
rash, rash erythematous, rash follicular, rash generalized, rash macular, rash maculo-papular, rash pruritic, rash pustular, skin disorder,
skin erosion, skin exfoliation, skin fissures, skin lesion, skin reaction, skin toxicity, skin ulcer.
d
Includes paronychia, nail infection, nail bed infection.
a
b
SELECTED IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Bullous and Exfoliative Skin Disorders (continued)
•Postmarketing cases of toxic epidermal necrolysis (TEN) and Stevens Johnson syndrome (SJS) have been
reported in patients receiving GILOTRIF. Discontinue GILOTRIF if TEN or SJS is suspected.
Please see additional Important Safety Information continued on
following pages. Click here for full Prescribing Information, including
Patient Information.
THINK DEL 19. THINK GILOTRIF.
4
GILOTRIF: The most common adverse reactions can usually
be managed through supportive care, dose modifications,
and discontinuations1,6-8
•The onset of diarrhea and skin reactions often occurs within the first 14 days of treatment
–83% of patients experienced diarrhea5
–64% of patients experienced rash/acne5
Serious adverse reactions1
•In LUX-Lung 3, serious adverse reactions were reported in 29% of patients treated with GILOTRIF.
The most frequent serious adverse reactions reported in patients treated with GILOTRIF were
diarrhea (6.6%); vomiting (4.8%); and dyspnea, fatigue, and hypokalemia (1.7% each). Fatal adverse
reactions in GILOTRIF-treated patients included pulmonary toxicity/ILD-like adverse reactions
(1.3%), sepsis (0.43%), and pneumonia (0.43%)
Discontinuations
•In LUX-Lung 3, discontinuation of therapy in GILOTRIF-treated patients for adverse reactions
was 14%1
•The most frequent adverse reactions that led to discontinuation in GILOTRIF-treated patients
were diarrhea (1.3%), ILD (0.9%), and paronychia (0.9%)1
SELECTED IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Interstitial Lung Disease
•Interstitial Lung Disease (ILD) or ILD-like adverse reactions (e.g., lung infiltration, pneumonitis, acute respiratory distress
syndrome, or alveolitis allergic) occurred in patients receiving GILOTRIF in clinical trials. In some cases, ILD was fatal.
The incidence of ILD appeared to be higher in Asian patients as compared to white patients.
•Withhold GILOTRIF during evaluation of patients with suspected ILD, and discontinue GILOTRIF in patients with
confirmed ILD.
Please see additional Important Safety Information continued on
following pages. Click here for full Prescribing Information, including
Patient Information.
THINK DEL 19. THINK GILOTRIF.
5
The most common adverse reactions—diarrhea, rash, stomatitis, and
paronychia—can usually be managed through supportive care, dose
modifications (including treatment interruptions), and discontinuations
Supportive care
Diarrhea
Rash/Acne
•Ensure adequate hydration8
•Use antidiarrheal agents
(eg, loperamide) as appropriate1
•Make antidiarrheal agents readily
available to patients so that treatment
can be initiated at first signs of
diarrhea and continued until loose
bowel movements cease for 12 hours1
•Advise patients to wear protective
clothing and/or use sunscreen to
minimize exposure to sun8
•Intervene early with emollients, and
topical steroids and/or antibiotics,
as appropriate8
•Consider additional therapeutic
intervention for patients with severe
or prolonged skin reactions8
Stomatitis
Paronychia
•Provide palliation through bland
saline rinses, topical lidocaine
anesthetics, mucosal coating agents,
and analgesics; the choice being
driven by patient preference6
•Consider treating paronychia with
silver nitrate or ferric subsulfate
solution, with soaks for symptomatic
relief. If infection is suspected,
culture sites and treat with
appropriate oral antibiotics7
SELECTED IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hepatic Toxicity
•Hepatic toxicity as evidenced by liver function tests abnormalities has been observed in patients taking GILOTRIF.
In 4257 patients who received GILOTRIF across clinical trials, 9.7% had liver test abnormalities, of which 0.2%
were fatal.
•Obtain periodic liver testing in patients during treatment with GILOTRIF. Withhold GILOTRIF in patients who
develop worsening of liver function. Treatment should be discontinued in patients who develop severe hepatic
impairment while taking GILOTRIF.
Please see additional Important Safety Information continued on
following pages. Click here for full Prescribing Information, including
Patient Information.
THINK DEL 19. THINK GILOTRIF.
6
GILOTRIF: Dose modification1,4
Initiate
therapy at the recommended 40-mg dose*
Evaluate
patients for adverse reactions within 2 weeks
and periodically thereafter
Pause
Resume
treatment for ≥ grade 3 adverse reactions
or ≥ grade 2
•diarrhea (prolonged)a,b
•cutaneous reactions (prolonged
or intolerable)a,c
•renal impairment
treatment at 10 mg less per day when adverse
reaction fully resolves, returns to baseline, or
improves to grade 1
*In patients with severe renal impairment, the recommended dose of GILOTRIF is 30 mg orally once daily.
National Cancer Institute Common Terminology Criteria for Adverse Events, v3.0.
Grade ≥2 diarrhea persisting ≥48 hours while taking antidiarrheal medication.
c
Grade 2 cutaneous reactions >7 days.
a
b
Permanently discontinue GILOTRIF for1:
Life-threatening bullous, blistering, or exfoliative skin lesions; confirmed ILD; severe drug-induced hepatic impairment;
persistent ulcerative keratitis; symptomatic left ventricular dysfunction; and severe or intolerable adverse reaction
occurring at a dose of 20 mg per day.
SELECTED IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Keratitis
•Keratitis has been reported in patients taking GILOTRIF.
•Withhold GILOTRIF during evaluation of patients with suspected keratitis. If diagnosis of ulcerative keratitis is
confirmed, treatment with GILOTRIF should be interrupted or discontinued. If keratitis is diagnosed, the benefits
and risks of continuing treatment should be carefully considered. GILOTRIF should be used with caution
in patients with a history of keratitis, ulcerative keratitis, or severe dry eye. Contact lens use is also a risk
factor for keratitis and ulceration.
Please see additional Important Safety Information continued on
following pages. Click here for full Prescribing Information, including
Patient Information.
THINK DEL 19. THINK GILOTRIF.
7
Supportive care, including dose modification, is an
important consideration when managing patients
LUX-Lung 3: Over half of patients reduced dose1,5
43
%
MAINTAINED
40-MG STARTING DOSE
38
%
REDUCED
TO 30 MG
19
%
FURTHER REDUCED
TO 20 MG
The majority of first dose reductions in LUX-Lung 3 occurred within the first
2 months of GILOTRIF treatment5
•LUX-Lung 3 included patients who remained on therapy at the recommended 40-mg once-daily dose,
and patients who started at the recommended dose, but subsequently required dose reductions9
SELECTED IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Embryo-Fetal Toxicity
•GILOTRIF can cause fetal harm when administered to a pregnant woman. 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, and for at least 2 weeks
after the last dose of GILOTRIF. Advise female patients to contact their healthcare provider with a known or
suspected pregnancy.
Please see additional Important Safety Information continued on
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Patient Information.
THINK DEL 19. THINK GILOTRIF.
8
GILOTRIF: Selected grade 3 adverse reactions
before and after dose modification
Grade 3 adverse reactions with dose modification1,10
25
Reported in ≥10% of all patients
After dose modification
20
Percent of patients
*Includes 1
patient with a
grade 4 event.
15
10
5
0
Diarrhea
Rash/Acne
Stomatitis*
Paronychia
Treatment-related grade 3 adverse reactions
•The most frequent adverse reactions that led to dose reduction in the patients treated with
GILOTRIF were diarrhea (20%), rash/acne (19%), paronychia (14%), and stomatitis (10%)1
In a post hoc analysis, PFS results were consistent among patients who required dose
reductions within the first 6 months and those who remained on GILOTRIF 40 mg9
SELECTED IMPORTANT SAFETY INFORMATION
ADVERSE REACTIONS
Adverse Reactions observed in clinical trials were as follows:
First-line treatment of EGFR mutation-positive, metastatic non-small cell lung cancer (NSCLC)
•In GILOTRIF-treated patients (n=229) the most common adverse reactions (≥20% all grades & vs pemetrexed/
cisplatin-treated patients (n=111)) were diarrhea (96% vs 23%), rash/acneiform dermatitis (90% vs 11%), stomatitis
(71% vs 15%), paronychia (58% vs 0%), dry skin (31% vs 2%), and pruritus (21% vs 1%). Other clinically important
adverse reactions observed in patients treated with GILOTRIF include: decreased appetite (29%), nausea (25%),
and vomiting (23%).
•Serious adverse reactions were reported in 29% of patients treated with GILOTRIF. The most frequent serious
adverse reactions reported in patients treated with GILOTRIF were diarrhea (6.6%); vomiting (4.8%); and dyspnea,
fatigue, and hypokalemia (1.7% each). Fatal adverse reactions in GILOTRIF-treated patients included pulmonary
toxicity/ILD-like adverse reactions (1.3%), sepsis (0.43%), and pneumonia (0.43%).
•More GILOTRIF-treated patients (2.2%) experienced ventricular dysfunction (defined as diastolic dysfunction, left
ventricular dysfunction, or ventricular dilation; all < Grade 3) compared to chemotherapy-treated patients (0.9%).
Please see additional Important Safety Information continued on
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Patient Information.
THINK DEL 19. THINK GILOTRIF.
9
IN ADVANCED SQUAMOUS CELL CARCINOMA OF THE LUNG
GILOTRIF: Significantly improved survival vs erlotinib1
Median OS: 7.9 months with GILOTRIF vs 6.8 months with erlotinib1
Overall survival (key secondary endpoint)
GILOTRIF (n=398)
Erlotinib (n=397)
100
7.9
13.6
months
months
Overall survival (%)
80
HR: 0.81 (95% CI, 0.69-0.95)
60
40
19% reduction
in risk of death
vs erlotinib
6.8
months
20
0
0
3
6
9
12
15
18
21
24
27
30
Time (months)
GILOTRIF: Significantly improved PFS vs erlotinib
•Median PFS: 2.4 months with afatinib vs 1.9 months with erlotinib (HR: 0.82; 95% CI, 0.68-0.99)1
•PFS benefit was consistent across clinically relevant subgroups11
LUX-Lung 8:
•Randomized, multicenter, open-label, active-controlled study evaluating GILOTRIF in patients with
metastatic squamous NSCLC with disease progression following ≥ 4 cycles of platinum-based chemotherapy
•Patients were randomized (1:1) to receive GILOTRIF 40 mg or erlotinib 150 mg orally once daily until progression
•Primary endpoint was PFS; secondary endpoints were OS, and objective response rate
SELECTED IMPORTANT SAFETY INFORMATION
ADVERSE REACTIONS
Adverse Reactions observed in clinical trials were as follows:
Previously Treated Metastatic Squamous NSCLC
•In GILOTRIF-treated patients (n=392) the most common adverse reactions (≥20% all grades & vs erlotinib-treated patients
(n=395)) were diarrhea (75% vs 41%), rash/acneiform dermatitis (70% vs 70%), stomatitis (30% vs 11%), decreased appetite
(25% vs 26%), and nausea (21% vs 16%).
•Serious adverse reactions were reported in 44% of patients treated with GILOTRIF. The most frequent serious
adverse reactions reported in patients treated with GILOTRIF were pneumonia (6.6%), diarrhea (4.6%),
and dehydration and dyspnea (3.1% each). Fatal adverse reactions in
GILOTRIF-treated patients included ILD (0.5%), pneumonia (0.3%),
respiratory failure (0.3%), acute renal failure (0.3%), and general
physical health deterioration (0.3%).
Please see additional Important Safety Information continued on
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THINK DEL 19. THINK GILOTRIF.
10
A similar proportion of patients had serious
adverse reactions in each group11
•44% of patients in each treatment arm experienced serious adverse reactions11
Adverse reactions reported in LUX-Lung 8 in ≥10% of GILOTRIF-treated patients1
GILOTRIF (n=392)
Erlotinib (n=395)
Adverse reaction
All grades, %
Grade 3-4, %
All grades, %
Grade 3-4, %
Gastrointestinal disorders
Diarrhea
Stomatitisa
Nausea
Vomiting
75
30
21
13
11
4
2
1
41
11
16
10
3
1
1
1
Skin and subcutaneous tissue disorders
Rash/acneiform dermatitisb
Pruritus
70
10
7
0
70
13
11
0
Infections
Paronychiac
11
1
5
0
25
3
26
2
Metabolism and nutrition disorders
Decreased appetite
Includes stomatitis, aphthous stomatitis, mucosal inflammation, mouth ulceration, oral mucosa erosion, mucosal
erosion, mucosal ulceration.
a
Includes acne, dermatitis, acneiform dermatitis, eczema, erythema, exfoliative rash, folliculitis, rash, rash generalized,
rash macular, rash maculo-papular, rash pruritic, rash pustular, skin exfoliation, skin fissures, skin lesion, skin reaction,
skin toxicity, skin ulcer.
b
Includes paronychia, nail infection, nail bed infection.
c
Treatment-related discontinuation due to any adverse reactions
was similar in both arms (20% vs 17% for GILOTRIF vs erlotinib)11
Discontinuation of therapy in GILOTRIF-treated patients for adverse reactions was 20%. The most
frequent adverse reactions that led to discontinuation in GILOTRIF-treated patients were diarrhea
(4.1%) and rash/acne (2.6%).1
Please see additional Important Safety Information continued on
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Patient Information.
THINK DEL 19. THINK GILOTRIF.
11
GILOTRIF: 40-mg, once-daily dosing1
Patient selection
•Select patients for the 1st-line treatment of mNSCLC with GILOTRIF based on the presence of Del 19 or
L858R mutations in tumor specimens
•Information on FDA-approved tests for the detection of EGFR mutations in NSCLC is available at:
http://www.fda.gov/CompanionDiagnostics
Recommended dose1
•The recommended dose is 40 mg orally once daily
•In patients with severe renal impairment, the
recommended dose of GILOTRIF is 30 mg orally
once daily*
*Estimated glomerular filtration rate [eGFR]
15 to 29 mL/min/1.73 m2.
How to take1
•Take GILOTRIF at least 1 hour before or 2 hours
after a meal
•Do not take a missed dose within 12 hours of
the next dose
Treatment duration1
•Treatment should be continued until disease progression or until no longer tolerated by the patient
Multiple strengths1
•Multiple tablet strengths are available for dose adjustment
GILOTRIF
40-mg tablet
GILOTRIF
30-mg tablet
GILOTRIF
20-mg tablet
Not actual size.
Not actual size.
Not actual size.
Please see information on dose modifications for drug-related adverse reactions on pages 6-9.
SELECTED IMPORTANT SAFETY INFORMATION
ADVERSE REACTIONS
Postmarketing Experience
Pancreatitis has been reported during post-marketing use of GILOTRIF. The frequency and causal relationship of
pancreatitis to GILOTRIF has not been established.
Please see additional Important Safety Information continued on
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THINK DEL 19. THINK GILOTRIF.
12
Drug-drug interactions
•GILOTRIF does not have a known impact on CYP450 enzymes1
•Cytochrome P450 liver enzymes (CYPs) metabolize ~90% of all medications12
•In vitro data indicated that drug-drug interactions with GILOTRIF due to inhibition or induction of
CYP450 enzymes by concomitant medications are unlikely1
•GILOTRIF is unlikely to affect the metabolism of other drugs that are substrates of CYP450 enzymes1
•Interactions with proton pump inhibitors are unlikely, as GILOTRIF is not metabolized via CYP450 enzymes,
and solubility of GILOTRIF is not affected by pH1,13
Effect of P-glycoprotein (P-gp) inhibitors and inducers1
•P-gp inhibitors (including but not limited to ritonavir, cyclosporine A, ketoconazole, itraconazole,
erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, and amiodarone) can increase exposure
to afatinib
•P-gp inducers (including but not limited to rifampicin, carbamazepine, phenytoin, phenobarbital, and
St. John’s wort) can decrease exposure to afatinib
For patients who require therapy with a P-gp inhibitor or inducer1
•P-gp inhibitors
–Reduce GILOTRIF daily dose by 10 mg if not tolerated. Resume the previous dose after discontinuation of
the P-gp inhibitor as tolerated
•P-gp inducers
–Increase GILOTRIF daily dose by 10 mg as tolerated. Resume the previous dose 2 to 3 days after
discontinuation of the P-gp inducer
SELECTED IMPORTANT SAFETY INFORMATION
DRUG INTERACTIONS
Effect of P-glycoprotein (P-gp) Inhibitors and Inducers
•Concomitant use of P-gp inhibitors (including but not limited to ritonavir, cyclosporine A, ketoconazole,
itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, and amiodarone) with GILOTRIF
can increase exposure to afatinib.
•Concomitant use of P-gp inducers (including but not limited to
rifampicin, carbamazepine, phenytoin, phenobarbital, and
St. John’s wort) with GILOTRIF can decrease exposure to afatinib.
Please see additional Important Safety Information continued on
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THINK DEL 19. THINK GILOTRIF.
13
Majority of patients in LUX-Lung 3 had Del 19 or L858R EGFR mutations1,14
Overall study population by mutation subtype1
49%
Del 19
(exon 19)
11%
Uncommon
40%
L858R
(exon 21)
LUX-Lung 3: Largest global trial in EGFR M+ mNSCLC to date3
•Randomized, multicenter, open-label trial that assessed the safety and efficacy of GILOTRIF 40 mg orally once daily
(n=230) vs up to 6 cycles of pemetrexed/cisplatin (n=115) as 1st-line therapy in patients with EGFR M+ mNSCLC1
•Primary endpoint was PFS; key secondary endpoint was OS4
Efficacy information in uncommon mutations (n=37)1
•There were 26 GILOTRIF-treated patients in the “other” (uncommon) EGFR mutations subgroup, which consisted of
9 unique mutation patterns1
•Median PFS: 2.8 months with GILOTRIF vs 9.9 months with pemetrexed/cisplatin (HR: 1.89; 95% CI, 0.84-4.28)1,15
•Median OS: 15.9 months with GILOTRIF vs 40.8 months with pemetrexed/cisplatin (HR: 2.35; 95% CI, 0.96-6.11)1,5
SELECTED IMPORTANT SAFETY INFORMATION
USE IN SPECIFIC POPULATIONS
Lactation
•Because of the potential for serious adverse reactions in nursing infants from GILOTRIF, lactating women should
not breastfeed during treatment with GILOTRIF and for 2 weeks after the final dose.
Females and Males of Reproductive Potential
•GILOTRIF may reduce fertility in females and males of reproductive potential. It is not known if the effects on
fertility are reversible.
Renal Impairment
•Patients with severe renal impairment (estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m2)
have a higher exposure to afatinib than patients with normal renal function. Administer GILOTRIF at a starting
dose of 30 mg once daily in patients with severe renal impairment. GILOTRIF has not been studied in patients
with eGFR <15 mL/min/1.73 m2 or who are on dialysis.
Hepatic Impairment
•GILOTRIF has not been studied in patients with severe (Child Pugh C) hepatic impairment. Closely monitor
patients with severe hepatic impairment and adjust GILOTRIF dose if not tolerated.
GF PROF ISI July 2016
Please see additional Important Safety Information starting on
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THINK DEL 19. THINK GILOTRIF.
14
TM
®
®
For patients prescribed GILOTRIF, Solutions Plus® offers
patient support from the start
Enroll your patients in Solutions Plus® by calling 1-877-814-3915 from 8am-8pm ET
To help with treatment initiation and continued adherence, all patients taking
GILOTRIF will receive a Patient Support Kit
Making patient support our priority by providing a broad range of access and clinical
support solutions for patients who are prescribed GILOTRIF
`
Access and Reimbursement Solutions for patients
Clinical Support Solutions for patients
•Coverage & reimbursement—assistance
with benefit verification, prior authorizations,
GILOTRIF Bridge*, denials, and appeals
•Patient Support Kit—patient resources to
help with treatment initiation and adherence
•Financial support—Co-pay Assistance
Program, alternative funding support, and
BI Cares Foundation
•Distribution—single, dedicated specialty
pharmacy partner (Accredo®) and select
on-site pharmacies
•GILOTRIF Pledge™—patient and
participating payers refunded for first month
of therapy if eligible† patients discontinue
before first refill
•Nurse support—real-time patient education
assistance from oncology-trained nurses to
complement care
•Pharmacy support—Accredo pharmacists
are available 24/7 to answer questions
related to GILOTRIF‡
•GILOTRIF Dose Exchange™—facilitates
transition to new dose, eliminates additional
GILOTRIF co-pay in a given month for
eligible patients§
*For commercially and publicly insured patients treated with GILOTRIF who may experience a payer delay >5 days for the
FDA-approved indication, or when a patient changes insurance and a treatment gap is expected.
†
For commercially insured patients serviced through Accredo who are participating in the Nurse Support Program.
‡
For patients serviced through Accredo.
§
GILOTRIF Dose ExchangeTM covers up to 2 dose modifications for patients serviced through Accredo or GILOTRIF
Dispensing Network who have 9 or more tablets to exchange.
Please see Important Safety Information starting on page 2.
Click here for full Prescribing Information, including Patient Information.
THINK DEL 19. THINK GILOTRIF.
15
IN 1ST-LINE EGFR M+ mNSCLC
Identify Del 19. Prescribe GILOTRIF 1st-line
EGFR
NCCN
CATEGORY
ARs
T 40
1st-line OS and PFS in Del 19, and PFS in L858R1,16
NCCN Category 1 recommendation
•Afatinib (GILOTRIF) has an NCCN Category 1 recommendation for 1st-line treatment of
mNSCLC patients with Del 19 or L858R mutations16
An established safety profile based on data from more than 4200 patients
in clinical trials1
40-mg, once-daily dosing1*
Solutions Plus®: Access and clinical support solutions for patients
•bisolutionsplus.com or call a Patient Care Advocate at 1-877-814-3915 from 8am-8pm ET
•Dedicated GILOTRIF team at Accredo® 1-844-569-2837 from 8:30am-7pm ET
SqCC
Significantly improved OS and PFS vs erlotinib in advanced squamous cell
carcinoma of the lung progressing after platinum-based chemotherapy1
*In patients with severe renal impairment, the recommended dose of GILOTRIF is 30 mg orally once daily.
INDICATIONS AND USAGE
GILOTRIF is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose
tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as
detected by an FDA-approved test.
Limitation of Use: Safety and efficacy of GILOTRIF have not been established in patients whose tumors have other
EGFR mutations.
GILOTRIF is indicated for the treatment of patients with metastatic squamous NSCLC progressing after platinum-based
chemotherapy.
Please see Important Safety Information starting on page 2. Click here for full Prescribing Information, including
Patient Information.
References: 1. Gilotrif® (afatinib) tablets Prescribing Information. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; April 2016.
2. Yang JC-H, Wu Y-L, Schuler M, et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3
and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015;16(2):141-151. 3. Lee CK, Wu YL, Ding PN,
et al. Impact of specific epidermal growth factor receptor (EGFR) mutations and clinical characteristics on outcomes after treatment with EGFR tyrosine
kinase inhibitors versus chemotherapy in EGFR-mutant lung cancer: a meta-analysis. J Clin Oncol. 2015;33(17):1958-1965. 4. Sequist LV, Yang JC,
Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations.
J Clin Oncol. 2013;31(27):3327-3334. 5. Data on file. Boehringer Ingelheim. CTR. 6. Bensinger W, Schubert M, Ang KK, et al. NCCN Task Force Report:
prevention and management of mucositis in cancer care. J Natl Compr Canc Netw. 2008;6(suppl 1):S1-S21. 7. Burtness B, Anadkat M, Basti S, et al. NCCN
Task Force Report: management of dermatologic and other toxicities associated with EGFR inhibition in patients with cancer. J Natl Compr Canc Netw.
2009;7(suppl 1):S5-S21. 8. Hirsh V. Managing treatment-related adverse events associated with EGFR tyrosine kinase inhibitors in advanced non-small-cell
lung cancer. Curr Oncol. 2011;18(3):126-138. 9. Yang J C-H, Ahn M-J, Dickgreber NJ, et al. Influence of dose adjustment on afatinib safety and efficacy
in patients with advanced EGFR mutation-positive NSCLC. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; May
29–June 2, 2015; Chicago, IL. 10. Yang JC, Sequist LV, O’Byrne KJ, et al. Epidermal growth factor receptor (EGFR)-mediated adverse events in patients
with EGFR mutation-positive non-small cell lung cancer (NSCLC) treated with afatinib. Poster presented at: ECCO17-ESMO38-ESTRO32 European Cancer
Congress; September 27–October 1, 2013; Amsterdam, The Netherlands. 11. Soria J-C, Felip E, Cobo M, et al. Afatinib versus erlotinib as second-line
treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol.
2015;16:897-907. 12. Lynch T, Price A. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician.
2007;76(3):391-396. 13. Peters S, Zimmermann S, Adjei AA. Oral epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small
cell lung cancer: comparative pharmacokinetics and drug-drug interactions. Cancer Treat Rev. 2014;40(8):917-926. 14. Sharma SV, Bell DW, Settleman J,
Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer. 2007;7(3):169-181. 15. Data on file. Boehringer Ingelheim. Other
mutations PFS table. 16. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: non-small cell lung cancer, version
4.2016. http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed July 25, 2016.
Boehringer Ingelheim Pharmaceuticals, Inc. either owns or uses the trademarks GILOTRIF®,
Solutions Plus®, GILOTRIF Pledge™, and GILOTRIF Dose Exchange™ under license.
Other referenced trademarks are owned by third parties.
Copyright ©2016. Boehringer Ingelheim Pharmaceuticals, Inc.
All rights reserved.
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PC-GF-0426-PROF
THINK DEL 19. THINK GILOTRIF.