In metastatic EGFRm NSCLC

Help your patients know what to expect

Educate them about the TAGRISSO safety profile

ADVERSE REACTIONS IN ≥ 10% OF TAGRISSO PATIENTS IN THE FLAURA TRIAL1*

TAGRISSO (n=279) erlotinib/gefitinib (n=277)
ADVERSE
REACTION 		Any grade
(%)		 Grade 3
or higher (%)		 Any grade
(%)		 Grade 3
or higher (%)
Gastrointestinal Disorders
Diarrhea† 58 2.2 57 2.5
Stomatitis 29 0.7 20 0.4
Nausea 14 0 19 0
Constipation 15 0 13 0
Vomiting 11 0 11 1.4
Skin Disorders
Rash‡ 58 1.1 78 6.9
Dry skin§ 36 0.4 36 1.1
Nail toxicityII 35 0.4 33 0.7
Pruritus 17 0.4 17 0
Metabolism and Nutrition Disorders
Decreased appetite 20 2.5 19 1.8
Respiratory, Thoracic, and Mediastinal Disorders
Cough 17 0 15 0.4
Dyspnea 13 0.4 7 1.4
Neurologic Disorders
Headache 12 0.4 7 0
Cardiac Disorders
Prolonged QT interval# 10 2.2 4 0.7
General Disorders and Administration Site Conditions
Fatigue** 21 1.4 15 1.4
Pyrexia 10 0 4 0.4
Infection and Infestation Disorders
Upper RT1 10 0 7 0

*NCI CTCAE v4.0.

†One grade 5 (fatal) event was reported (diarrhea) for EGFR-TKI comparator (erlotinib or gefitinib).

‡Includes rash, rash generalized, rash erythematous, rash macular, rash maculopapular, rash papular, rash pustular, rash pruritic, rash vesicular, rash follicular, erythema, folliculitis, acne, dermatitis, dermatitis acneiform, drug eruption, skin erosion.

§Includes dry skin, skin fissures, xerosis, eczema, xeroderma.

IIIncludes nail bed disorder, nail bed inflammation, nail bed infection, nail discoloration, nail pigmentation, nail disorder, nail toxicity, nail dystrophy, nail infection, nail ridging, onychalgia, onychoclasis, onycholysis, onychomadesis, onychomalacia, paronychia.

Includes pruritus, pruritus generalized, eyelid pruritus.

#The frequency of “Prolonged QT Interval” represents reported adverse events in the FLAURA study. Frequencies of QTc intervals of >500 ms or >60 ms are presented in Section 5.2 of the Prescribing Information.

**Includes fatigue, asthenia.

RTI, respiratory tract infection.

The majority of adverse reactions reported in the FLAURA study were Grade 1 or 21,2

NCI Adverse Event Grades

Grade 1
Mild; no symptoms or only mild symptoms; no intervention necessary

Grade 2
Moderate; minimal intervention required

Grade 3
Severe/medically significant, but not life-threatening; may require hospitalization

Grade 4
Life-threatening; urgent intervention required

Grade 5
Death

NCI Adverse Event Grades

Grade 1
Mild; no symptoms or only mild symptoms; no intervention necessary

Grade 2
Moderate; minimal intervention required

Grade 3
Severe/medically significant, but not life-threatening; may require hospitalization

Grade 4
Life-threatening; urgent intervention required

Grade 5
Death

  • Grade 3 and 4 ARs require more serious intervention, including stopping or even discontinuing therapy3
  • The median duration of exposure to TAGRISSO was 16.2 months compared to 11.5 months in the erlotinib or gefitinib arm2
  • In FLAURA, 2.9% of trial participants treated with once-daily TAGRISSO required a dose reduction due to adverse reactions1

Partner with patients to anticipate and manage adverse reactions

  • Uncommon but serious adverse reactions can occur while taking TAGRISSO, including ILD/pneumonitis, QTc interval prolongation, cardiomyopathy, keratitis, erythema multiforme and Stevens-Johnson syndrome, and embryo-fetal toxicity
  • Tell your patients to notify you or their oncologist right away if they have trouble breathing, new or worsening cough, fever, dizziness, lightheadedness, fainting, target lesions (skin reactions that look like rings), severe blistering, or peeling of skin

Adverse Reactions

Potential ILD

  • New or worsening
  • Trouble breathing
  • Shortness of breath
  • Cough
  • Fever

actions

  • Patients should immediately stop taking TAGRISSO
  • Alert physician of possible interstitial lung disease (ILD)
  • TAGRISSO should be PERMANENTLY DISCONTINUED if ILD is confirmed

Potential QTC Interval prolongation/SYMPTOMATIC CONGESTIVE HEART FAILURE

  • Dizziness
  • Lightheadedness
  • Fainting (syncope)
  • Heart is pounding or racing
  • If QTc interval is greater than 500 msec on at least 2 separate ECGs, withhold TAGRISSO until QTc interval is less than 481 msec or recovery to baseline. However, if baseline QTc is greater than or equal to 481 msec, then resume at 40 mg dose
  • TAGRISSO should be PERMANENTLY DISCONTINUED in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia
  • Permanently discontinue TAGRISSO in patients with symptomatic congestive heart failure

Stevens-Johnson Syndrome (SJS), Erythema Multiforme Major (EMM)

  • Target lesions
  • Severe blistering
  • Peeling of skin
  • Withhold TAGRISSO if suspected and permanently discontinue if confirmed

any grade 3 or greater
adverse reaction

  • TAGRISSO should be withheld for up to 3 weeks; if improvement to Grades 0-2 within 3 weeks, it should be resumed at 80 mg or 40 mg daily
  • If no improvement within 3 weeks, TAGRISSO should be PERMANENTLY DISCONTINUED

Adverse Reactions

Potential ILD

  • New or worsening
  • Trouble breathing
  • Shortness of breath
  • Cough
  • Fever

actions

  • Patients should immediately stop taking TAGRISSO
  • Alert physician of possible interstitial lung disease (ILD)
  • TAGRISSO should be PERMANENTLY DISCONTINUED if ILD is confirmed

Adverse Reactions

Potential QTC
Interval prolongation/SYMPTOMATIC CONGESTIVE HEART FAILURE

  • Dizziness
  • Lightheadedness
  • Fainting (syncope)
  • Heart is pounding or racing

actions

  • If QTc interval is greater than 500 msec on at least 2 separate ECGs, withhold TAGRISSO until QTc interval is less than 481 msec or recovery to baseline. However, if baseline QTc is greater than or equal to 481 msec, then resume at 40 mg dose
  • TAGRISSO should be PERMANENTLY DISCONTINUED in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia
  • Permanently discontinue TAGRISSO in patients with symptomatic congestive heart failure

Adverse Reactions

Stevens-Johnson Syndrome (SJS), Erythema Multiforme Major (EMM)

  • Target lesions
  • Severe blistering
  • Peeling of skin

actions

  • Withhold TAGRISSO if suspected and permanently discontinue if confirmed

Adverse Reactions

any grade 3 or greater
adverse reaction

actions

  • TAGRISSO should be withheld for up to 3 weeks; if improvement to Grades 0-2 within 3 weeks, it should be resumed at 80 mg or 40 mg daily
  • If no improvement within 3 weeks, TAGRISSO should be permanently discontinued

Taking action early may help resolve adverse reactions for optimal treatment

Monitor patients during treatment with TAGRISSO1

if your patient

Has congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or takes medication known to prolong the QTc interval

actions

  • Periodic monitoring should be conducted with ECGs and electrolytes

Has cardiac risk factors

  • Cardiac monitoring should be conducted, including assessment of LVEF at baseline and during treatment

if your patient

Has congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or takes medication known to prolong the QTc interval

actions

  • Periodic monitoring should be conducted with ECGs and electrolytes

if your patient

Has cardiac risk factors

actions

  • Cardiac monitoring should be conducted, including assessment of LVEF at baseline and during treatment

What to know about drug interactions1

EFFECT OF OTHER DRUGS ON TAGRISSO1

Reduced exposure to drug. Increased exposure to drug. No effect
CATEGORY EFFECT INTERVENTION
CATEGORYStrong CYP3A inducers
(rifampin/rifampicin, antibiotic, eg, Rifadin)		 EFFECT78% reduction in AUC of TAGRISSO INTERVENTION

Avoid

if possible; if not possible, increase TAGRISSO to 160 mg daily

Resume

TAGRISSO at 80 mg 3 weeks after discontinuation of the strong CYP3A4 inducer
CATEGORYStrong CYP3A inhibitors
(itraconazole, antifungal, eg, Sporanox)		 EFFECTNo clinically significant effect INTERVENTIONNo intervention needed
CATEGORYGastric acid reducing agents
(omeprazole, eg, Prilosec)		 EFFECTNot affected INTERVENTIONNo intervention needed
EFFECT OF TAGRISSO ON OTHER DRUGS1
CATEGORYBCRP substrates
(rosuvastatin, statin, eg, CRESTOR)		 EFFECT35% increase in AUC of BCRP substrate INTERVENTION

Monitor

for side effects of the BCRP substrate
CATEGORYP-GP substrates
(fexofenadine, eg, Allegra)		 EFFECT56% increase in AUC of P-GP substrate after a single dose, and 27% at steady state INTERVENTION

Monitor

for side effects of the P-GP substrate
CATEGORYCYP3A4 substrates
(simvastatin, statin, eg, Zocor)		 EFFECTNo clinically significant effect INTERVENTIONNo intervention needed

AUC, area under the curve; BCRP, breast cancer resistance protein; CYP, cytochrome P450; P-GP, P-glycoprotein.

ARs, adverse reactions; ECGs, electrocardiograms; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutant; LVEF, left ventricular ejection fraction; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; NSCLC, non-small cell lung cancer; QTc, heart rate-corrected QT interval; TKI, tyrosine kinase inhibitor.

References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020. 2. Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf#search=%22ctcae%22. Accessed October 3, 2019. 3. Soria JC, Ohe Y, Vansteenkiste J, et al; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113-125.

IMPORTANT SAFETY INFORMATION

  • There are no contraindications for TAGRISSO
  • Interstitial lung disease (ILD)/pneumonitis occurred in 3.7% of the 1479 TAGRISSO-treated patients; 0.3% of cases were fatal. Withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (eg, dyspnea, cough and fever). Permanently discontinue TAGRISSO if ILD is confirmed
  • Heart rate-corrected QT (QTc) interval prolongation occurred in TAGRISSO-treated patients. Of the 1479 TAGRISSO-treated patients in clinical trials, 0.8% were found to have a QTc >500 msec, and 3.1% of patients had an increase from baseline QTc >60 msec. No QTc-related arrhythmias were reported. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia
  • Cardiomyopathy occurred in 3% of the 1479 TAGRISSO-treated patients; 0.1% of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) ≥10% from baseline and to <50% LVEF occurred in 3.2% of 1233 patients who had baseline and at least one follow-up LVEF assessment. In the ADAURA study, 1.5% (5/325) of TAGRISSO-treated patients experienced LVEF decreases ≥10% from baseline and a drop to <50%. Conduct cardiac monitoring, including assessment of LVEF at baseline and during treatment, in patients with cardiac risk factors. Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment. For symptomatic congestive heart failure, permanently discontinue TAGRISSO
  • Keratitis was reported in 0.7% of 1479 patients treated with TAGRISSO in clinical trials. Promptly refer patients with signs and symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye) to an ophthalmologist
  • Postmarketing cases consistent with Stevens-Johnson syndrome (SJS) and erythema multiforme major (EMM) have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if SJS or EMM is suspected and permanently discontinue if confirmed
  • Postmarketing cases of cutaneous vasculitis including leukocytoclastic vasculitis, urticarial vasculitis, and IgA vasculitis have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if cutaneous vasculitis is suspected, evaluate for systemic involvement, and consider dermatology consultation. If no other etiology can be identified, consider permanent discontinuation of TAGRISSO based on severity
  • Verify pregnancy status of females of reproductive potential prior to initiating TAGRISSO. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAGRISSO and for 6 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the final dose
  • Most common (≥20%) adverse reactions, including laboratory abnormalities, were leukopenia, lymphopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough

INDICATIONS

  • TAGRISSO is indicated as adjuvant therapy after tumor resection in adult patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test

  • TAGRISSO is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test

  • TAGRISSO is indicated for the treatment of adult patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy

For additional information, please see the complete Prescribing Information, including Patient Information.

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