
In resectable EGFRm NSCLC
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
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
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
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
Grade 1Mild; no symptoms or only mild symptoms; no intervention necessary
Grade 2Moderate; minimal intervention required
Grade 3Severe/medically significant, but not life-threatening; may require hospitalization
Grade 4Life-threatening; urgent intervention required
Grade 5Death
Grade 1Mild; no symptoms or only mild symptoms; no intervention necessary
Grade 2Moderate; minimal intervention required
Grade 3Severe/medically significant, but not life-threatening; may require hospitalization
Grade 4Life-threatening; urgent intervention required
Grade 5Death
In resectable and metastatic EGFRm NSCLC
Partner with patients to help anticipate and manage adverse reactions1
Adverse Reactions
Potential ILD
actions
Potential QTC Interval prolongation/SYMPTOMATIC CONGESTIVE HEART FAILURE
Stevens-Johnson Syndrome (SJS), Erythema Multiforme Major (EMM)
any grade 3 or greater adverse reaction
Adverse Reactions
Potential ILD
actions
Adverse Reactions
Potential QTC
Interval
prolongation/
SYMPTOMATIC
CONGESTIVE HEART
FAILURE
actions
Adverse Reactions
Stevens-Johnson Syndrome (SJS), Erythema Multiforme Major (EMM)
actions
Adverse Reactions
any grade 3 or greateradverse reaction
actions
Taking action early may help resolve adverse reactions for optimal treatment
In resectable and metastatic EGFRm NSCLC
Monitor patients during treatment with TAGRISSO
if your patient
Has congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or takes medication known to prolong the QTc interval
actions
Has cardiac 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
if your patient
Has cardiac risk
factors
actions
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 dailyResume 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.
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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