In resectable EGFRm NSCLC

Adjuvant TAGRISSO: Safety profile was consistent with established profile

The majority of adverse reactions were Grade 1 or 21

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

TAGRISSO (n=337) CONTROL ARM (n=343)
ADVERSE REACTION All Grades (%) Grade 3 or higher†
(%)		 All Grades (%) Grade 3 or higher†
(%)
Gastrointestinal
Disorders
Diarrhea‡ 47 2.4 20 0.3
Stomatitis§ 32 1.8 7 0
Abdominal painII 12 0.3 7 0
Skin Disorders
Rash 40 0.6 19 0
Nail toxicity# 37 0.9 3.8 0
Dry skin** 29 0.3 7 0
Pruritus†† 19 0 9 0
Respiratory, Thoracic and Mediastinal Disorders
Cough‡‡ 19 0 19 0
Musculoskeletal and Connective Tissue Disorders
Musculoskeletal pain§§ 18 0.3 25 0.3
Infection and Infestation Disorders
Nasopharyngitis 14 0 10 0
Upper respiratory tract infection 13 0.6 10 0
Urinary tract infectionIIII 10 0.3 7 0
General Disorders and Administration Site Conditions
Fatigue¶¶ 13 0.6 9 0.3
Nervous System Disorders
Dizziness## 10 0 9 0
Metabolism and Nutrition Disorders
Decreased appetite 13 0.6 3.8 0

No Grade 4 or 5 ARs reported with adjuvant TAGRISSO or placebo among the above mentioned ARs.

In addition, clinically relevant adverse reactions in ADAURA that occurred in <10% of patients receiving TAGRISSO were alopecia (6%), epistaxis (6%), interstitial lung disease (3%), palmar-plantar erythrodysesthesia syndrome (1.8%), keratitis (0.6%), QTc interval prolongation (0.6%), and erythema multiforme (0.3%). QTc interval prolongation represents the incidence of patients who had a QTcF prolongation >500 msec.1

In ADAURA, the discontinuation rate due to adverse reactions was 11% with TAGRISSO.*** Adverse reactions leading to dose reductions occurred in 9% of patients on TAGRISSO1†††

Diarrhea was the most common adverse reaction observed in TAGRISSO-treated patients.1 With TAGRISSO, the median time to onset of diarrhea was 22 days, and the median duration of Grade 2 diarrhea was 11 days2

*NCI CTCAE v4.0.

†All events were Grade 3.

‡Includes diarrhea, colitis, enterocolitis, enteritis.

§Includes aphthous ulcer, cheilitis, gingival ulceration, glossitis, tongue ulceration, stomatitis, and mouth ulceration.

IIIncludes abdominal discomfort, abdominal pain, abdominal lower pain, abdominal upper pain, epigastric discomfort, hepatic pain.

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, dermatitis bullous, dermatitis exfoliative generalized, drug eruption, eczema, eczema asteatotic, lichen planus, skin erosion, pustule.

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

††Includes pruritus, pruritus generalized, eyelid pruritus.

‡‡Includes cough, productive cough, upper-airway cough syndrome.

§§Includes arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, pain in extremity, and spinal pain.

IIIIIncludes cystitis, urinary tract infection, and urinary tract infection bacterial.

¶¶Includes asthenia, fatigue.

##Includes dizziness, vertigo, and vertigo positional.

***The most frequent adverse reactions leading to discontinuation of TAGRISSO were interstitial lung disease (2.7%) and rash (1.2%).

†††The most frequent adverse reactions leading to dose reductions or interruptions were diarrhea (4.5%), stomatitis (3.9%), nail toxicity (1.8%), and rash (1.8%).

It’s important to help your patients manage adverse reactions while taking TAGRISSO. Taking action early may help resolve adverse reactions for optimal treatment

In resectable EGFRm NSCLC

Adjuvant TAGRISSO: Safety profile was consistent with established safety profile

The majority of laboratory abnormalities were Grade 1 or 21

LABORATORY ABNORMALITIES WORSENING FROM BASELINE IN ≥20% OF PATIENTS IN ADAURA

TAGRISSO (n=337) Placebo (n=343)
Laboratory Abnormality*† All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%)
Hematology
Leukopenia 54 0 25 0
Thrombocytopenia 47 0 7 0.3
Lymphopenia 44 3.4 14 0.9
Anemia 30 0 12 0.3
Neutropenia 26 0.6 10 0.3
Chemistry
Hyperglycemia 25 2.3 30 0.9
Hypermagnesemia 24 1.3 14 1.5
Hyponatremia 20 1.8 16 1.5

In addition, the laboratory abnormality in ADAURA that occurred in <20% of patients receiving TAGRISSO was increased blood creatinine (10%).

*NCI CTCAE v4.0.

†Based on the number of patients with available follow-up laboratory data.

In metastatic EGFRm NSCLC

First-line TAGRISSO: Safety matters in FLAURA

The majority of TAGRISSO adverse reactions were Grade 1 or 21

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‡ 32 0.7 22 1.1
Nausea 14 0 19 0
Constipation 15 0 13 0
Vomiting 11 0 11 1.4
Skin Disorders
Rash§ 58 1.1 78 7
Dry skinII 36 0.4 36 1.1
Nail toxicity 35 0.4 33 0.7
Pruritus# 17 0.4 17 0
General Disorders and Administration Site Conditions
Fatigue** 21 1.4 15 1.4
Pyrexia 10 0 4 0.4
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
Infection and Infestation Disorders
Upper RT1 10 0 7 0

Clinically relevant adverse reactions in FLAURA in <10% of patients receiving TAGRISSO were alopecia (7%), epistaxis (6%), interstitial lung disease (3.9%), palmar-plantar erythrodysesthesia syndrome (1.4%), QTc interval prolongation (1.1%), and keratitis (0.4%). QTc interval prolongation represents the incidence of patients who had a QTcF prolongation >500 msec.1

Adverse reaction data are based on median duration of therapy of 16.2 months for first-line TAGRISSO and 11.5 months for erlotinib/gefitinib.3

  • In FLAURA, 2.9% of patients treated with once-daily TAGRISSO had a dose reduction1

The clinically relevant laboratory abnormality in FLAURA that occurred in <20% of patients receiving TAGRISSO was increased blood creatinine (9%).1


At 3 years, 28% of patients were still being treated with TAGRISSO vs 9% with erlotinib/gefitinib4‡‡

*NCI CTCAE v4.0.

†One Grade 5 (fatal) event was reported (diarrhea) for EGFR-TKI comparator.

‡Includes stomatitis and mouth ulceration.

§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, pustule.

IIIncludes dry skin, skin fissures, xerosis, eczema, xeroderma.

Includes 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.

**Includes fatigue, asthenia.

††Includes prolonged QT interval reported as adverse reaction.

‡‡In the FLAURA trial, treatment beyond the point of disease progression was allowed as long as there was continued clinical benefit, as judged by the investigator.3

In resectable and metastatic EGFRm NSCLC

The majority of adverse reactions reported in the FLAURA study were Grade 1 or 21,5

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 therapy1

In resectable and metastatic EGFRm NSCLC

Partner with patients to help anticipate and manage adverse reactions1

  • Uncommon but serious adverse reactions can occur while taking TAGRISSO, including ILD/pneumonitis, QTc interval prolongation, cardiomyopathy, keratitis, erythema multiforme and Stevens-Johnson syndrome, cutaneous vasculitis, and embryo-fetal toxicity
  • Use recommended dose modifications to help manage serious adverse reactions if they occur
  • Tell your patients to notify you or their oncologist right away if they have trouble breathing, a new or worsening cough, fever, dizziness, lightheadedness, fainting, target lesions (skin reactions that look like rings), severe blistering, peeling of skin, or purple spots or redness of your skin or large hives that do not go away within 24 hours and look bruised

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

In resectable and metastatic EGFRm NSCLC

Monitor patients during treatment with TAGRISSO

  • Monitor patients who take certain medicines or who have CV risk factors

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

In resectable and metastatic EGFRm NSCLC

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

ARs, adverse reactions; AUC, area under the curve; BCRP, breast cancer resistance protein; CTCAE, Common Terminology Criteria for Adverse Events; CV, cardiovascular; CYP, cytochrome P450; ECG, electrocardiogram; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation positive; ILD, interstitial lung disease; LVEF, left ventricular ejection fraction; L858R, exon 21 leucine 858 arginine substitution; msec, millisecond; NCI, National Cancer Institute; NSCLC, non-small cell lung cancer; P-GP, P-glycoprotein; RTI, respiratory tract infection; T790M, exon 20 threonine 790 methionine substitution; TKI, tyrosine kinase inhibitor.

References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020. 2. Data on File. REF-89081. TAGRISSO (osimertinib)—statement on diarrhoea. AstraZeneca Pharmaceuticals LP. 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. 4. Ramalingam SS, Vansteenkiste J, Planchard D, et al; FLAURA Investigators. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2020;382(1):41-50. 5. US Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) v4.03. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf. Published May 28, 2009. Accessed June 14, 2010.

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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