Metastatic Non-Small
Cell Lung Cancer
Metastatic Non-Small Cell Lung Cancer
For tumors with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 substitution mutations
For metastatic squamous non-small cell lung cancer (NSCLC) progressing after platinum-based chemotherapy

Approaches to the management of metastatic non-small cell lung cancer (mNSCLC) are evolving. Let's look at three possible journeys.

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.

Metastatic Non-Small Cell Lung Cancer
For tumors with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 substitution mutations
For metastatic squamous non-small cell lung cancer (NSCLC) progressing after platinum-based chemotherapy
Metastatic Non-Small Cell
Lung Cancer
For tumors with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 substitution mutations
For metastatic squamous non-small cell lung cancer (NSCLC) progressing after platinum-based chemotherapy

Approaches to the management of metastatic non-small cell lung cancer (mNSCLC) are evolving. Let's look at three possible journeys.

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.

*Not an actual patient.
Paul H.*

EGFR exon 19 deletion
(Del 19)

*Not an actual patient.

Rebecca T.*

EGFR exon 21 substitution
(L858R)

*Not an actual patient.

*Not an actual patient.
George N.*

Squamous cell carcinoma

*Not an actual patient.

Rebecca T.* *Not an actual patient.
Metastatic Non-Small Cell Lung
Cancer Patient: Rebecca T.
History and initial evaluation
  • 52-year-old real estate agent
  • Loves adventurous cooking, traveling, and writing
  • Tobacco status: current smoker (12 pack-years)
  • Lung abnormalities detected in routine shoulder x-ray
Rebecca’s goal is to
publish a travel cookbook.
Paul H.* *Not an actual patient.
Metastatic Non-Small Cell
Lung Cancer Patient: Paul H.
History and presenting symptoms
  • 64-year-old retired police detective
  • Married 39 years
  • Active golfer
  • Tobacco status: quit smoking at age 59 (40 pack-years)
  • Persistent cough, shortness of breath
Paul’s goal is to celebrate his
40th wedding anniversary with his family.
George N.* *Not an actual patient.
Squamous Cell Carcinoma
Patient: George N.
History
  • 67 years old
  • Lives over 40 miles from town
  • Tobacco status: down to ½ pack per day (45 pack-years)
George’s goal is to spend more time
at home with friends and family.

Comorbid conditions and medications

  • Gastroesophageal reflux disease: taking esomeprazole magnesium, a proton pump inhibitor (PPI)
  • Hyperlipidemia: taking atorvastatin, a cytochrome P450-metabolized HMG-CoA* reductase inhibitor (statin)

Initial workup conducted by Rebecca’s oncologist

  • CT scan shows multiple bilateral nodules in the lungs, visceral pleura, and lymph nodes

Diagnosis

  • Biopsy confirms adenocarcinoma of the lung
  • Stage IV; Eastern Cooperative Oncology Group Performance Status: 0
*3-hydroxy-3-methyl-glutaryl-
co-enzyme-A.

NCCN guidelines1 recommend EGFR or ALK testing as part of broad molecular profiling for patients with metastatic adenocarcinoma NSCLC.

Rebecca’s biomarker testing report

  • Rebecca’s oncologist performed an FDA-approved biomarker test, which detected EGFR exon 21 substitution (L858R) mutations in Rebecca’s tumor specimens

In the United States, approximately 15% of patients have adenocarcinomas that harbor EGFR-activating mutations.2,3

GILOTRIF tablets are indicated as first-line treatment of patients with mNSCLC whose tumors have EGFR L858R substitution mutations as detected by an FDA-approved test.4 GILOTRIF has a Category 1 NCCN recommendation for the first-line treatment of patients with EGFR mutation-positive (M+) Stage IV NSCLC.1

FOR THE FIRST-LINE TREATMENT OF mNSCLC WITH EGFR L858R MUTATIONS

GILOTRIF tablets: Approved treatment option for patients with L858R mutations4,5

Median overall survival (OS) in LUX-Lung 3
L858R mutation populationa
  • 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)
27.6 months
40.3 months
HR: 1.30 (95% CI, 0.80-2.11)
HR: 1.30 (95% CI, 0.80-2.11)
Overall survival (%)
Time of overall survival (OS) (months)

FOR THE FIRST-LINE TREATMENT OF mNSCLC WITH L858R EGFR MUTATIONS

GILOTRIF tablets: Approved treatment option with proven PFS for patients with L858R mutations4,6,7

Median PFS for L858R (exon 21) mutations (n=138)a,b
HR: 0.73 (95% CI, 0.46-1.17)
Time (months)
GILOTRIF Pemetrexed/cisplatin

Efficacy information in uncommon mutations (n=37)4

Limitation of Use: Safety and efficacy of GILOTRIF have not been established in patients whose tumors have other EGFR mutations.

  • Median PFS: 2.8 months with GILOTRIF vs 9.9 months with pemetrexed/cisplatin (HR: 1.89; 95% CI, 0.84-4.28)4,8
  • Median OS: 15.9 months with GILOTRIF vs 40.8 months with pemetrexed/cisplatin (HR: 2.35; 95% CI, 0.96-6.11)4,7

GILOTRIF has an NCCN Category 1 recommendation for first-line treatment of mNSCLC in patients with Del 19 or L858R mutations.1

Adverse reactions in LUX-Lung 3, a pivotal study for GILOTRIF6

Adverse reactions reported in LUX-Lung 3 in ≥10% of GILOTRIF-treated patients4

Adverse reaction GILOTRIF (n=229) Pemetrexed/cisplatin (n=111)
All grades, % Grade 3a, % All grades, % Grade 3a, %
Gastrointestinal disorders
Diarrhea 96 15 23 2
Stomatitisb 71 9 15 1
Cheilitis 12 0 1 0
Skin and subcutaneous tissue disorders
Rash/acneiform dermatitisc 90 16 11 0
Pruritus 21 0 1 0
Dry skin 31 0 2 0
Infections
Paronychiad 58 11 0 0
Cystitis 13 1 5 0
Respiratory, thoracic, and mediastinal disorders
Epistaxis 17 0 2 1
Rhinorrhea 11 0 6 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
Adverse reaction GILOTRIF
(n=229)
All grades, % Grade 3a, %
Gastrointestinal disorders
Diarrhea 96 15
Stomatitisb 71 9
Cheilitis 12 0
Skin and subcutaneous tissue disorders
Rash/acneiform dermatitisc 90 16
Pruritus 21 0
Dry skin 31 0
Infections
Paronychiad 58 11
Cystitis 13 1
Respiratory, thoracic, and mediastinal disorders
Epistaxis 17 0
Rhinorrhea 11 0
Investigations
Weight decreased 17 1
General disorders and administration site conditions
Pyrexia 12 0
Eye disorders
Conjunctivitis 11 0
Adverse reaction Pemetrexed/cisplatin
(n=111)
All grades, % Grade 3a, %
Gastrointestinal disorders
Diarrhea 23 2
Stomatitisb 15 1
Cheilitis 1 0
Skin and subcutaneous tissue disorders
Rash/acneiform dermatitisc 11 0
Pruritus 1 0
Dry skin 2 0
Infections
Paronychiad 0 0
Cystitis 5 0
Respiratory, thoracic, and mediastinal disorders
Epistaxis 2 1
Rhinorrhea 6 0
Investigations
Weight decreased 14 1
General disorders and administration site conditions
Pyrexia 6 0
Eye disorders
Conjunctivitis 3 0
Other clinically important adverse reactions observed in patients treated with GILOTRIF include decreased appetite (29%), nausea (25%), and vomiting (23%).4

aNone of the adverse reactions in this table except stomatitis (1 patient on GILOTRIF [0.4%]) were grade 4 in severity.

bIncludes stomatitis, aphthous stomatitis, mucosal inflammation, mouth ulceration, oral mucosa erosion, mucosal erosion, mucosal ulceration.

cIncludes 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.

dIncludes paronychia, nail infection, nail bed infection.

Serious adverse reactions in LUX-Lung 34

Adverse reaction GILOTRIF
Diarrhea 6.6%
Vomiting 4.8%
Dyspnea 1.7%
Fatigue 1.7%
Hypokalemia 1.7%
  • Serious adverse reactions were reported in 29% of patients treated with GILOTRIF
  • Fatal adverse reactions in GILOTRIF-treated patients included pulmonary toxicity/interstitial lung disease-like adverse reactions (1.3%), sepsis (0.43%), and pneumonia (0.43%)
  • More GILOTRIF-treated patients (2.2%; n=5) experienced ventricular dysfunction (defined as diastolic dysfunction, left ventricular dysfunction, or ventricular dilation; all less than grade 3) than chemotherapy-treated patients (0.9%)
  • Pancreatitis has been reported during postmarketing use of GILOTRIF. The frequency and causal relationship of pancreatitis to GILOTRIF has not been established

Schedule a 2-week check-in with Rebecca

Rebecca was started on GILOTRIF 40 mg

  • GILOTRIF was effective for patients like Rebecca in the LUX-Lung 3 study; there are no known drug interactions with her PPI or hyperlipidemia medications4

Rebecca’s 2-week check-in visit

  • Reports persistent mild diarrhea
  • Reduced appetite
  • Papular eruptions on upper arm, but little itching

The onset of diarrhea and skin reaction often occurs within the first 2 weeks of GILOTRIF initiation.7

Rebecca’s follow-up visit

Rebecca’s CT scan confirms disease control
(tumor shrinkage noted)

She continues on GILOTRIF 40 mg

Her diarrhea reduced to occasional grade 1 (mild) with loperamide and dietary modifications

Rash successfully treated with topical steroid cream

She reported stomatitis at 3 months that was treated with a mouth rinse and diet modifications

Rebecca presents her doctor with a signed
copy of her new cookbook.

Summary: How the journey begins could determine how far they go

First-line OS and PFS in Del 19, and PFS in L858R1,4
NCCN Category 1 recommendation
GILOTRIF has an NCCN Category 1 recommendation for first-line treatment of mNSCLC patients with Del 19 or L858R mutations1

Patient counseling
tips for your staff

  • Educate patients that adverse events are expected with GILOTRIF4
  • Discuss proactive measures such as diet modification and skin protection9
  • Advise patients to call your office immediately if they experience diarrhea or rash
  • Review other potential adverse events and treatment strategies
An established safety profile based on data from more than 4200 patients in clinical trials4
40-mg, once-daily dosing4
The recommended dose of GILOTRIF in patients with severe renal impairment (estimated glomerular filtration rate 15 to 29 mL/min/1.73 m2) is 30 mg orally, once daily
Schedule a 2-week check-in with your patients after the start of therapy
Solutions Plus®: Access and clinical support solutions for patients
www.bisolutionsplus.com or call a Patient Care Advocate at 1-877-814-3915 from 8:00am to 8:00pm ET
Dedicated GILOTRIF team at Accredo® 1-844-569-2837 from 8:30am to 7:00pm ET
Accredo is a registered trademark.

References

  • National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN Guidelines). Non-small cell lung cancer (Version 4.2016). https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed September 26, 2016.
  • Bernicker E. Biomarker testing in non-small cell lung cancer. Arch Pathol Lab Med. 2015;139:448-450.
  • 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.
  • Gilotrif® (afatinib) tablets Prescribing Information. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; October 2016.
  • 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.
  • 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.
  • Data on file. Boehringer Ingelheim. CTR.
  • Data on file. Boehringer Ingelheim. Other mutations PFS table.
  • 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.

Comorbid conditions and medications

  • Epilepsy: taking carbamazepine, a P-glycoprotein (P-gp) inducer
  • Hypertension: taking nifedipine, a cytochrome P450-metabolized calcium-channel blocker
  • Gastroesophageal reflux disease: taking esomeprazole magnesium, a proton pump inhibitor (PPI)

Initial workup conducted by Paul’s oncologist

  • Chest x-ray detects abnormalities
  • MRI scan confirms multiple lesions

Diagnosis

  • Needle biopsy confirms diagnosis of adenocarcinoma of the lung
  • Stage IV; Eastern Cooperative Oncology Group Performance Status: 1
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People who answered YES 23%
People who answered NO 32%
Answer: YES

NCCN guidelines1 recommend EGFR or ALK testing as part of broad molecular profiling for patients with metastatic adenocarcinoma NSCLC.

Paul’s biomarker testing report

  • Paul’s oncologist performed an FDA-approved biomarker test, which detected EGFR exon 19 deletion mutations in Paul’s tumor specimens.

In the United States, approximately 15% of patients have adenocarcinomas that harbor EGFR-activating mutations.2,3 In the LUX-Lung 3 study, GILOTRIF was shown to have significantly improved progression-free survival (PFS) compared with pemetrexed/cisplatin in patients with EGFR exon 19 deletions.4-6

GILOTRIF tablets are indicated as first-line treatment of patients with mNSCLC whose tumors have EGFR exon 19 deletions as detected by an FDA-approved test.4 GILOTRIF has a Category 1 NCCN recommendation for the first-line treatment of patients with EGFR mutation-positive (M+) Stage IV NSCLC.1

FOR THE FIRST-LINE TREATMENT OF EGFR M+ mNSCLC VS CHEMOTHERAPY

GILOTRIF tablets: Only agent with proven overall survival (OS) in patients with Del 19 mutations3,4,7

Median OS in LUX-Lung 3
Del 19 mutation populationa
  • 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)
45% reduction
in risk of death
21.1 months
33.3 months
HR: 0.55 (95% CI, 0.36-0.79)
HR: 0.55 (95% CI, 0.36-0.79)
Overall survival (%)
Time of overall survival (months)

FOR THE FIRST-LINE TREATMENT OF EGFR M+ mNSCLC VS CHEMOTHERAPY

GILOTRIF: Treatment option with proven PFS for patients with Del 19 mutations4-6

Median PFS for Del 19 mutations (n=170)a,b
HR: 0.28 (95% CI, 0.18-0.44)
Time (months)
GILOTRIF Pemetrexed/cisplatin

Efficacy information in uncommon mutations (n=37)4

Limitation of Use: Safety and efficacy of GILOTRIF have not been established in patients whose tumors have other EGFR mutations.

  • Median PFS: 2.8 months with GILOTRIF vs 9.9 months with pemetrexed/cisplatin (HR: 1.89; 95% CI, 0.84-4.28)4,8
  • Median OS: 15.9 months with GILOTRIF vs 40.8 months with pemetrexed/cisplatin (HR: 2.35; 95% CI, 0.96-6.11)4,6

GILOTRIF has an NCCN Category 1 recommendation for first-line treatment of mNSCLC in patients with Del 19 or L858R mutations.1

Adverse reactions in LUX-Lung 3, a pivotal study for GILOTRIF5

Adverse reactions reported in LUX-Lung 3 in ≥10% of GILOTRIF-treated patients4

Adverse reaction GILOTRIF (n=229) Pemetrexed/cisplatin (n=111)
All grades, % Grade 3a, % All grades, % Grade 3a, %
Gastrointestinal disorders
Diarrhea 96 15 23 2
Stomatitisb 71 9 15 1
Cheilitis 12 0 1 0
Skin and subcutaneous tissue disorders
Rash/acneiform dermatitisc 90 16 11 0
Pruritus 21 0 1 0
Dry skin 31 0 2 0
Infections
Paronychiad 58 11 0 0
Cystitis 13 1 5 0
Respiratory, thoracic, and mediastinal disorders
Epistaxis 17 0 2 1
Rhinorrhea 11 0 6 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
Adverse reaction GILOTRIF
(n=229)
All grades, % Grade 3a, %
Gastrointestinal disorders
Diarrhea 96 15
Stomatitisb 71 9
Cheilitis 12 0
Skin and subcutaneous tissue disorders
Rash/acneiform dermatitisc 90 16
Pruritus 21 0
Dry skin 31 0
Infections
Paronychiad 58 11
Cystitis 13 1
Respiratory, thoracic, and mediastinal disorders
Epistaxis 17 0
Rhinorrhea 11 0
Investigations
Weight decreased 17 1
General disorders and administration site conditions
Pyrexia 12 0
Eye disorders
Conjunctivitis 11 0
Adverse reaction Pemetrexed/cisplatin
(n=111)
All grades, % Grade 3a, %
Gastrointestinal disorders
Diarrhea 23 2
Stomatitisb 15 1
Cheilitis 1 0
Skin and subcutaneous tissue disorders
Rash/acneiform dermatitisc 11 0
Pruritus 1 0
Dry skin 2 0
Infections
Paronychiad 0 0
Cystitis 5 0
Respiratory, thoracic, and mediastinal disorders
Epistaxis 2 1
Rhinorrhea 6 0
Investigations
Weight decreased 14 1
General disorders and administration site conditions
Pyrexia 6 0
Eye disorders
Conjunctivitis 3 0
Other clinically important adverse reactions observed in patients treated with GILOTRIF include decreased appetite (29%), nausea (25%), and vomiting (23%).4

aNone of the adverse reactions in this table except stomatitis (1 patient on GILOTRIF [0.4%]) were grade 4 in severity.

bIncludes stomatitis, aphthous stomatitis, mucosal inflammation, mouth ulceration, oral mucosa erosion, mucosal erosion, mucosal ulceration.

cIncludes 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.

dIncludes paronychia, nail infection, nail bed infection.

Serious adverse reactions in LUX-Lung 34

Adverse reaction GILOTRIF
Diarrhea 6.6%
Vomiting 4.8%
Dyspnea 1.7%
Fatigue 1.7%
Hypokalemia 1.7%
  • Serious adverse reactions were reported in 29% of patients treated with GILOTRIF
  • Fatal adverse reactions in GILOTRIF-treated patients included pulmonary toxicity/interstitial lung disease-like adverse reactions (1.3%), sepsis (0.43%), and pneumonia (0.43%)
  • More GILOTRIF-treated patients (2.2%; n=5) experienced ventricular dysfunction (defined as diastolic dysfunction, left ventricular dysfunction, or ventricular dilation; all less than grade 3) than chemotherapy-treated patients (0.9%)
  • Pancreatitis has been reported during postmarketing use of GILOTRIF. The frequency and causal relationship of pancreatitis to GILOTRIF has not been established

Schedule a 2-week check-in with Paul

Paul was started on GILOTRIF 40 mg

  • GILOTRIF was effective for patients like Paul in the LUX-Lung 3 study; it should not affect the metabolism of his hypertension medication4
  • Paul was closely monitored for drug interactions between GILOTRIF and carbamazepine, a P-gp inducer
  • There are no known drug interactions with his PPI4

Paul’s 2-week check-in visit

  • Reports persistent worsening diarrhea despite taking antidiarrheal medication
  • Grade 3 diarrhea of approximately 8 stools per day
  • Maculopapular rash on upper arms, chest, and back, with itching

The onset of diarrhea and skin reaction often occurs within the first 2 weeks of GILOTRIF initiation.6

Managing Paul’s diarrhea

  • Paul’s GILOTRIF was paused for 10 days, then restarted at 30 mg, using the GILOTRIF Dose Exchange™ program

Paul’s follow-up visit

Paul’s CT scan confirms disease control, no new lesions detected

He continues on GILOTRIF 30 mg per day

His diarrhea reduced to occasional grade 1 (mild)

Rash successfully treated with oral antibiotics and topical therapies

Paul’s children and grandchildren are planning a
40th wedding anniversary party.

Summary: How the journey begins could determine how far they go

First-line OS and PFS in Del 19, and PFS in L858R1,4
NCCN Category 1 recommendation
GILOTRIF has an NCCN Category 1 recommendation for first-line treatment of mNSCLC patients with Del 19 or L858R mutations1

Patient counseling
tips for your staff

  • Educate patients that adverse events are expected with GILOTRIF4
  • Discuss proactive measures such as diet modification and skin protection9
  • Advise patients to call your office immediately if they experience diarrhea or rash or rash
  • Review other potential adverse events and treatment strategies
  • Inform patients that dose modifications were common in LUX-Lung 34
An established safety profile based on data from more than 4200 patients in clinical trials4
40-mg, once-daily dosing4
The recommended dose of GILOTRIF in patients with severe renal impairment (estimated glomerular filtration rate 15 to 29 mL/min/1.73 m2) is 30 mg orally, once daily.
Schedule a 2-week check-in with your patients after the start of therapy
Solutions Plus®: Access and clinical support solutions for patients
www.bisolutionsplus.com or call a Patient Care Advocate at 1-877-814-3915 from 8:00am to 8:00pm ET
Dedicated GILOTRIF team at Accredo® 1-844-569-2837 from 8:30am to 7:00pm ET
Accredo is a registered trademark.

References

  • National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN Guidelines). Non-small cell lung cancer (Version 4.2016). https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed September 26, 2016.
  • Bernicker E. Biomarker testing in non-small cell lung cancer. Arch Pathol Lab Med. 2015;139:448-450.
  • 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.
  • Gilotrif® (afatinib) tablets Prescribing Information. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; October 2016.
  • 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.
  • Data on file. Boehringer Ingelheim. CTR.
  • 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.
  • Data on file. Boehringer Ingelheim. Other mutations PFS table.
  • 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.

Diagnosis and Treatment History

  • Stage IV squamous cell carcinoma (SqCC) of the lung
  • Eastern Cooperative Oncology Group Performance Status: 1
  • He progressed after first-line treatment with a platinum-based doublet chemotherapy (6 cycles)

In patients with NSCLC, EGFR mutations and anaplastic lymphoma kinase (ALK) rearrangements appear only sporadically in patients who present with squamous histology.1 As a result, NCCN guidelines recommend EGFR or ALK testing in a minority of patients with metastatic SqCC – those that never smoked, and those with small biopsy specimens or mixed histology.2 Thus, George's oncologist determined that such testing was not necessary.

GILOTRIF is approved for the treatment of patients with advanced SqCC of the lung whose disease has progressed after treatment with platinum-based chemotherapy.3,4

IN ADVANCED SqCC OF THE LUNG

GILOTRIF significantly improved survival vs erlotinib3

LUX-Lung 8: Head-to-head study vs erlotinib in patients with metastatic SqCC4

  • Randomized, multicenter, open-label phase III trial that assessed the safety and efficacy of GILOTRIF 40 mg orally once daily (n=398) vs erlotinib 150 mg once daily (n=397) in patients with metastatic squamous NSCLC with disease progression after ≥4 cycles of platinum-based chemotherapy
  • Primary endpoint was PFS; key secondary endpoint was OS

Median overall survival (OS): 7.9 months with GILOTRIF vs 6.8 months with erlotinib3

OS (key secondary endpoint) in LUX-Lung 8
  • GILOTRIF
    (n=398)
  • Erlotinib
    (n=397)
19% reduction in risk of death vs erlotinib
6.8 months
7.9 months
HR: 0.81 (95% CI, 0.69-0.95)
HR: 0.81 (95% CI, 0.69-0.95)
Overall survival (%)
Time (months)

GILOTRIF significantly improved progression-free survival (PFS) vs erlotiniba

  • Median PFS: 2.4 months with GILOTRIF vs 1.9 months with erlotinib (HR: 0.82; 95% CI, 0.68-0.99)3

aPrimary endpoint was PFS, by independent review.

GILOTRIF is indicated for the treatment of patients with metastatic squamous NSCLC progressing after platinum-based chemotherapy.

Adverse reactions reported in LUX-Lung 8 in ≥10% of GILOTRIF-treated patients3

Adverse reaction GILOTRIF (n=392) Erlotinib (n=395)
All grades, % Grade 3-4, % All grades, % Grade 3-4, %
Gastrointestinal disorders
Diarrhea 75 11 41 3
Stomatitisa 30 4 11 1
Nausea 21 2 16 1
Vomiting 13 1 10 1
Skin and subcutaneous tissue disorders
Rash/acneiform dermatitisb 70 7 70 11
Pruritus 10 0 13 0
Infections
Paronychiac 11 1 5 0
Metabolism and nutrition disorders
Decreased appetite 25 3 26 2
Adverse reaction GILOTRIF (n=392)
All grades, % Grade 3-4, %
Gastrointestinal disorders
Diarrhea 75 11
Stomatitisa 30 4
Nausea 21 2
Vomiting 13 1
Skin and subcutaneous tissue disorders
Rash/acneiform dermatitisb 70 7
Pruritus 10 0
Infections
Paronychiac 11 1
Metabolism and nutrition disorders
Decreased appetite 25 3
Adverse reaction Erlotinib (n=395)
All grades, % Grade 3-4, %
Gastrointestinal disorders
Diarrhea 41 3
Stomatitisa 11 1
Nausea 16 1
Vomiting 10 1
Skin and subcutaneous tissue disorders
Rash/acneiform dermatitisb 70 11
Pruritus 13 0
Infections
Paronychiac 5 0
Metabolism and nutrition disorders
Decreased appetite 26 2

aIncludes stomatitis, aphthous stomatitis, mucosal inflammation, mouth ulceration, oral mucosa erosion, mucosal erosion, mucosal ulceration.

bIncludes 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.

cIncludes paronychia, nail infection, nail bed infection.

A similar proportion of patients had serious adverse reactions in each group4

  • In LUX-Lung 8, the most common serious adverse reactions in patients treated with GILOTRIF were pneumonia (6.6%), diarrhea (4.6%), and dehydration and dyspnea (3.1% each).
  • 44% of patients in each treatment arm experienced serious adverse reactions.4

Treatment-related discontinuation due to any adverse reactions was similar in both arms (20% vs 17% for GILOTRIF vs erlotinib)4

  • 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%)3

George’s follow-up visit

  • George was started on GILOTRIF 40 mg
George is looking forward to spending
more time with his friends and family.

Summary: How the journey begins could determine how far they go

Significantly improved OS and PFS vs erlotinib in advanced SqCC of the lung3
An established safety profile based on data from more than 4200 patients in clinical trials3

Patient counseling
tips for your staff

  • Educate patients that adverse events are expected with GILOTRIF3
  • Discuss proactive measures such as diet modification and skin protection5
  • Advise patients to call your office immediately if they experience diarrhea or rash
  • Review other potential adverse events and treatment strategies
40-mg, once-daily dosing3
The recommended dose of GILOTRIF in patients with severe renal impairment (estimated glomerular filtration rate 15 to 29 mL/min/1.73 m2) is 30 mg orally, once daily
Solutions Plus®: access and clinical support solutions for patients
www.bisolutionsplus.com or call a Patient Care Advocate at 1-877-814-3915 from 8:00am to 8:00pm ET
Dedicated GILOTRIF team at Accredo® 1-844-569-2837 from 8:30am to 7:00pm ET
Accredo is a registered trademark.

References

  • Chia PL, Mitchell P, Dobrovic A, John T. Prevalence and natural history of ALK positive non-small-cell lung cancer and the clinical impact of targeted therapy with ALK inhibitors. Clin Epidemiol. 2014;6:423-432.
  • National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN Guidelines). Non-small cell lung cancer (Version 4.2016). https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed October 10, 2016.
  • Gilotrif® (afatinib) tablets Prescribing Information. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; October 2016.
  • 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(8):897-907.
  • 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.
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Metastatic Non-Small Cell Lung Cancer