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GILOTRIF® (afatinib): the only oral, chemo-free option approved for patients with squamous mNSCLC progressing after a platinum-based regimen1,7

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Video

Watch a video of Dr. Mark Socinski sharing his perspectives on use of GILOTRIF in the treatment of patients with squamous mNSCLC progressing after a platinum-based chemotherapy regimen, as early as second line.

ONLY ORAL OPTION

Consider GILOTRIF as early as second-line as the only oral, chemo-free option for patients with metastatic squamous NSCLC who progressed after platinum-based chemotherapy1,7,28

No biomarker testing required1,7

Treatment options in later lines of therapy1,28†:

Gilotrif tablet icon

GILOTRIF
additional lines of chemotherapy icon

ADDITIONAL LINES OF CHEMOTHERAPY
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BEST SUPPORTIVE CARE

The only FDA-approved oral treatment option for patients with metastatic squamous NSCLC progressing after platinum-based chemotherapy1,7

GILOTRIF may be appropriate for patients who have1,29:

Been diagnosed with metastatic squamous NSCLC

Been treated with a combination platinum-based chemotherapy regimen

Experienced disease progression after first-line platinum-based chemotherapy

†For certain patients who did not receive I/O in first-line, this therapy is available in second-line.

LUX-LUNG 8 STUDY DATA

GILOTRIF showed significant improvement in progression-free survival (PFS) and overall survival (OS) vs erlotinib in LUX-Lung 81‡

Median PFS and median OS in LUX-Lung 81,7

Median PFS in LUX Lung 8
Median OS in LUX Lung 8

‡In LUX-Lung 8, a head-to-head Phase III trial vs erlotinib in patients with metastatic SqCC of the lung with disease progression following >4 cycles of platinum-based chemotherapy. The primary endpoint was progression-free survival and overall survival was a secondary endpoint.1,7

Disease Control for GILOTRIF vs erlotinib in LUX-Lung 87, §

51% (201/398) of patients treated with GILOTRIF were able to achieve disease control vs 40% (157/397) with erlotinib7,§

Excluding patients with non-complete response and non- progressive disease, disease control with afatinib was 37% (146/398), vs 29% (114/397) with erlotinib, in a post hoc analysis7,§

  • Median duration of objective response: 7.3 months (95% CI, 3.7-16.5) with GILOTRIF vs 3.7 months (95% CI, 2.6-10.2) with erlotinib7
51 percent icon

§In LUX-Lung 8, disease control (defined as complete response, partial response, stable disease, non-complete response, and non-progressive disease) was a secondary endpoint.1,7

Estimated Survival Rates

Kaplan-Meier estimates of survival at 6, 12, and 18 months in LUX-Lung 81,7

Chart Kaplan-Meier Estimates of Survival

Adverse reactions (ARs) reported in LUX-Lung 8 in ≥10% of GILOTRIF treated patients1*

Adverse reactionGILOTRIF (n=392) Grade 3-4, %Erlotinib (n=395) Grade 3-4, %GILOTRIF (n=392) All grades, %Erlotinib (n=395) All grades, %
Gastrointestinal disorders
Diarrhea1137541
Stomatitis†413011
Nausea212116
Vomiting111310
Skin and subcutaneous tissue disorders
Rash/acneiform dermatitis‡7117070
Pruritus001013
Metabolism and nutrition disorders
Decreased appetite322526
Infections
Paronychia§10115

AR=adverse reaction.

*NCI CTCAE v3.0.

†Includes stomatitis, aphthous stomatitis, mucosal inflammation, mouth ulceration, oral mucosa erosion, mucosal erosion, mucosal ulceration.

‡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.

§Includes paronychia, nail infection, nail bed infection.

Serious ARs Reported in LUX-Lung 81

  • Serious ARs occurred in 44% of patients treated with GILOTRIF. The most frequent serious ARs in patients treated with GILOTRIF were pneumonia (6.6%), diarrhea (4.6%), and dehydration and dyspnea (3.1% each). Fatal ARs 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%)

Treatment-related discontinuation due to any adverse reactions was similar in both arms (20% vs 17% for GILOTRIF vs erlotinib)7

  • 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

LUX-Lung 81,7
  • A head-to-head, phase 3, open-label, randomized trial of GILOTRIF 40 mg (n=398) vs erlotinib 150 mg (n=397) in patients with metastatic squamous NSCLC with disease progression following ≥4 cycles of platinum-based chemotherapy
  • Primary endpoint was PFS as assessed by an IRC using RECIST v1.1
  • Secondary endpoints included OS and objective response rates as assessed by an IRC

In an exploratory, retrospective ad-hoc analysis of LUX-Lung 8, observed benefits of GILOTRIF were more pronounced in squamous NSCLC patients with ErbB mutations30

Association of ErbB mutations with clinical outcomes of GILOTRIF-treated patients with lung squamous cell carcinoma—secondary analysis of the LUX-Lung 8 randomized clinical trial30

  • In an exploratory retrospective analysis of LUX-Lung 8, researchers developed a hypothesis that may explain differential responses seen in this patient population. The clinical significance has not been determined30

Median PFS and median OS in GILOTRIF-treated patients with and without ErbB mutations30

median PFS and OS Goss data in Gilotrif
  • ErbB Family proteins drive oncogenesis and can be mutated or overexpressed in patients with NSCLC30-32
  • Afatinib covalently binds to the kinase domains of EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4) and irreversibly inhibits tyrosine kinase autophosphorylation, resulting in downregulation of ErbB signaling1
  • In LUX-Lung 8, 22% of patients with samples available for analysis had tumors with 1 or more ErbB mutations (53/245 patients). Specimens were retrospectively selected and enriched for patients with PFS >2 months to ensure the data set reflected a range of responsiveness to TKIs30

LUX-Lung 81,7 
  • A head-to-head, phase 3, open-label, randomized trial of GILOTRIF 40 mg (n=398) vs erlotinib 150 mg (n=397) in patients with metastatic squamous NSCLC with disease progression following ≥4 cycles of platinum-based chemotherapy
  • Primary endpoint was PFS as assessed by an IRC using RECIST v1.1
  • Secondary endpoints included OS and objective response rates as assessed by an IRC
An ad hoc secondary analysis of LUX-Lung 830
  • An ad hoc, retrospective, secondary analysis of LUX-Lung 8 in which tumor samples (n=245) collected during the trial were extracted for DNA to assess EGFR expression levels and associations of PFS and OS with ErbB gene alterations and EGFR expression levels
  • Specimens for tumor genetic analysis (TGA) were retrospectively selected and enriched for patients with PFS >2 months to ensure that the data set reflected a range of responsiveness to EGFR-targeted tyrosine kinase inhibitors

Mechanism of action: Irreversible inhibition of ErbB receptor family signaling by GILOTRIF34

Gilotrif mechanism of action

The clinical significance of the mechanism of action has not been established.

REAL-WORLD STUDY DATA

Real-world squamous mNSCLC outcomes with GILOTRIF following first-line (1L) pembrolizumab plus platinum-based chemotherapy36

The objectives of this real-world study were to determine time on second-line (2L) GILOTRIF treatment for squamous mNSCLC patients who progressed on 1L immunotherapy (IO) plus platinum-based chemotherapy and incidence of severe immune-related adverse events (irAEs). Time on treatment was defined as time from start to end of 2L treatment on GILOTRIF; severe irAEs were defined as Grade 3/4.

Study design

Physicians retrospectively abstracted data from medical records of adult patients (n=200) with advanced/ metastatic NSCLC of squamous or mixed histology who had received 1L treatment with pembrolizumab plus platinum-based chemotherapy, followed by 2L GILOTRIF or chemotherapy.

Results are not intended for direct comparison with clinical trials. Differences in study designs, patient populations, definitions of safety or efficacy outcomes, as well as data collection methods, make it difficult to compare real-world studies with clinical trials.

Limitations

This study reports real-world data from retrospective medical chart reviews. It is intended to supplement, not replace, randomized controlled clinical trials. The limitations of this study include: 1) Potential for significant patient selection bias due to its retrospective nature and risk of under-reporting of adverse events including unverified severe irAEs; 2) The study was not powered to formally compare outcomes between cohorts; 3) Risk of censoring bias (54% of afatinib-treated/41% of non-afatinib treated still receiving 2L at data collection); 4) All data were abstracted by trained physicians personally managing each patient and source EMR data were not reviewed; 5) Confounding factors that might have influenced prescribing behaviors and treatment decisions were not captured. See publication for complete list of study limitations.36

Median time on treatment from initiation of 2L therapy36

The study was not powered to compare characteristics or outcomes between the 2L afatinib and 2L chemotherapy cohorts.

Please note that this study is real-world data, not the results of a randomized clinical trial and is provided for informational purposes, not to be the basis of treatment decision. Treatment decisions should be based on clinical experience and Prescribing Information.

median time on afatinib and chemo

Immune-related adverse events (irAEs) in patients treated with GILOTRIF following 1L pembrolizumab plus platinum-based chemotherapy36

PatientirAE in first lineirAE in second line
1Grade 3 pneumonitisGrade 4 pneumonitis
2Grade 3 hepatitisGrade 2 hepatitis
3Grade 3 colitisGrade 3 pneumonitis
4Grade 3 pneumonitisGrade 3 colitis
5Grade 3 indeterminant pulmonary eventGrade 3 pneumonitis
6Grade 3 pneumonitisGrade 3 colitis

6 patients had Grade 3/4 immune-related adverse events (irAEs included colitis, hepatitis, and pneumonitis) during 2L GILOTRIF treatment; all 6 patients previously had a Grade 3/4 irAE during 1L therapy.3

Other AEs (≥5%), n (%), 2L GILOTRIF (n=99)

Any AEs37 (37%)
Diarrhea*26 (26%)
Skin rash6 (6%)
Stomatitis5 (5%)
Fatigue5 (5%)

*The most common adverse drug reaction in the 2L GILOTRIF cohort was diarrhea.

Consider GILOTRIF as early as second-line as the only oral, chemo-free option for your squamous mNSCLC patients who have progressed after platinum-based chemotherapy1,7,28

I/O=immuno-oncology; NSCLC=non-small cell lung cancer; SqCC=squamous cell carcinoma; CI=confidence interval; HR=hazard ratio; OS=overall survival; PFS=progression-free survival; IRC=independent review committee; RECIST=Response Evaluation Criteria in Solid Tumors; MOA=mechanism of action; TKIs=tyrosine kinase inhibitors.

INDICATIONS AND USAGE

GILOTRIF is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have non-resistant epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test.

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

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

IMPORTANT SAFETY INFORMATION FOR GILOTRIF® (afatinib) TABLETS 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.
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 skin 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.
  • 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.
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.
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. Discontinue treatment in patients who develop severe hepatic impairment while taking GILOTRIF.
Gastrointestinal Perforation
  • Gastrointestinal (GI) perforation, including fatal cases, has occurred with GILOTRIF. GI perforation has been reported in 0.2% of patients treated with GILOTRIF among 3213 patients across 17 randomized controlled clinical trials.
  • Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or anti-angiogenic agents, or patients with increasing age or who have an underlying history of GI ulceration, underlying diverticular disease, or bowel metastases may be at an increased risk of perforation.
  • Permanently discontinue GILOTRIF in patients who develop GI perforation.
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, interrupt or discontinue GILOTRIF. 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.
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.
ADVERSE REACTIONS
Adverse Reactions observed in clinical trials were as follows:
First-line treatment of EGFR mutation-positive, metastatic 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%).
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%).
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.
USE IN SPECIFIC POPULATIONS
Lactation
  • Because of the potential for serious adverse reactions in breastfed infants from GILOTRIF, advise women not to 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 10.21.19

Please see full Prescribing Information, including Patient Information.

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NCCN=National Comprehensive Cancer Network® (NCCN®).