SAFETY

Please see the serious Warnings and Precautions associated with IMFINZI® (durvalumab).

Adverse Reactions

Similar incidence of Grades 3 or 4 adverse reactions in the IMFINZI® (durvalumab) and placebo arms1*

Adverse reactions reported in ≥10% of patients in the PACIFIC study1

Adverse reaction

IMFINZI (n=475)

  • All grades (%)
  • Grades 3-4 (%)

Placebo (n=234)

  • All grades (%)
  • Grades 3-4 (%)

Respiratory, thoracic, and mediastinal disorders

Cough/productive cough

  • 40%
  • 0.6%
  • 30%
  • 0.4%

Pneumonitis/radiation pneumonitis

  • 34%
  • 3.4%
  • 25%
  • 3%

Dyspnea

  • 25%
  • 1.5%
  • 25%
  • 2.6%

Gastrointestinal disorders

Diarrhea

  • 18%
  • 0.6%
  • 19%
  • 1.3%

Abdominal pain§

  • 10%
  • 0.4%
  • 6%
  • 0.4%

Endocrine disorders

HypothyroidismII

  • 12%
  • 0.2%
  • 1.7%
  • 0%

Skin and subcutaneous tissue disorders

Rash

  • 23%
  • 0.6%
  • 12%
  • 0%

Pruritus#

  • 12%
  • 0%
  • 6%
  • 0%

General disorders

Fatigue**

  • 34%
  • 0.8%
  • 32%
  • 1.3%

Pyrexia

  • 15%
  • 0.2%
  • 9%
  • 0%

Infections

Upper respiratory tract infections††

  • 26%
  • 0.4%
  • 19%
  • 0%

Pneumonia‡‡

  • 17%
  • 7%
  • 12%
  • 6%
  • At the time of the primary 2-year overall survival analysis, the safety and tolerability profile for IMFINZI remained consistent with that reported at the time of the primary PFS analysis2
  • Serious adverse reactions occurred in 29% of patients receiving IMFINZI and in 23% of patients receiving placebo. The most frequent serious adverse reactions (≥2%) with IMFINZI were pneumonitis or radiation pneumonitis (7%) and pneumonia (6%)1,3
  • Fatal pneumonitis or radiation pneumonitis and fatal pneumonia occurred in <2% of patients and were similar across arms1
  • Pneumonitis or radiation pneumonitis led to discontinuation in 6% of patients receiving IMFINZI1

*The PACIFIC study was not designed to demonstrate a statistically significant difference in adverse reaction rates for IMFINZI, as compared to placebo, for any specific adverse reaction.1

Includes acute interstitial pneumonitis, interstitial lung disease, pneumonitis, and pulmonary fibrosis.1

Includes dyspnea and exertional dyspnea.1

§Includes abdominal pain, abdominal pain lower, abdominal pain upper, and flank pain.1

IIIncludes autoimmune hypothyroidism and hypothyroidism.1

Includes rash erythematous, rash generalized, rash macular, rash maculopapular, rash papular, rash pruritic, rash pustular, erythema, eczema, rash, and dermatitis.1

#Includes pruritus generalized and pruritus.1

**Includes asthenia and fatigue.1

††Includes laryngitis, nasopharyngitis, peritonsillar abscess, pharyngitis, rhinitis, sinusitis, tonsillitis, tracheobronchitis, and upper respiratory tract infection.1

‡‡Includes lung infection, pneumocystis jirovecii pneumonia, pneumonia, pneumonia adenoviral, pneumonia bacterial, pneumonia cytomegaloviral, pneumonia haemophilus, pneumonia klebsiella, pneumonia necrotizing, pneumonia pneumococcal, and pneumonia streptococcal.1

 

Discontinuation Rates

Discontinuation rates due to adverse events, regardless of causality3

 

Immune-Mediated Adverse Events

Early identification and proper management of immune-mediated adverse events (imAEs) may help patients resume treatment1,4

  • imAEs of any grade, regardless of cause, were reported in 24% of patients taking IMFINZI vs 8% of patients taking placebo3
 

See the IMFINZI Immune-Mediated Adverse Events Handbook for detailed information about best management practices

 

Laboratory Abnormalities

Incidence of laboratory abnormalities in the IMFINZI® (durvalumab) and placebo arms1

Laboratory abnormalities worsening from baseline occurring in ≥20% of patients

Laboratory abnormalities

IMFINZI

  • All grades*
  • Grades 3 or 4

Placebo

  • All grades*
  • Grades 3 or 4

Chemistry

Hyperglycemia

  • 52%
  • 8%
  • 51%
  • 8%

Hypocalcemia

  • 46%
  • 0.2%
  • 41%
  • 0%

Increased ALT

  • 39%
  • 2.3%
  • 22%
  • 0.4%

Increased AST

  • 36%
  • 2.8%
  • 21%
  • 0.4%

Hyponatremia

  • 33%
  • 3.6%
  • 30%
  • 3.1%

Hyperkalemia

  • 32%
  • 1.1%
  • 29%
  • 1.8%

Increased GGT

  • 24%
  • 3.4%
  • 22%
  • 1.7%

Hematology

Lymphopenia

  • 43%
  • 17%
  • 39%
  • 18%

ALT=alanine aminotransferase; AST=aspartate aminotransferase; GGT=gamma-glutamyl transferase; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events.

*Graded according to NCI CTCAE version 4.0.1

Each test incidence is based on the number of patients who had both baseline and at least 1 on-study laboratory measurement available: IMFINZI (range: 464-470) and placebo (range: 224-228).1

 

Help your patients monitor their treatment experience, including immune-mediated adverse events, by calling 1-855-LHOUSE1 (1-855-546-8731)

 

Important Safety Information

There are no contraindications for IMFINZI® (durvalumab).

IMFINZI can cause serious, potentially fatal adverse reactions including immune-mediated pneumonitis, hepatitis, colitis, endocrinopathies, nephritis, dermatologic reactions, other immune-mediated adverse reactions, infection, and infusion-related reactions. Please refer to the full Prescribing Information for important dosage modification and management information specific to adverse reactions.

Indication

IMFINZI is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.

Immune-Mediated Pneumonitis

IMFINZI can cause immune-mediated pneumonitis, defined as requiring use of corticosteroids. Fatal cases have been reported. Monitor patients for signs and symptoms of pneumonitis and evaluate with radiographic imaging when suspected. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold IMFINZI for Grade 2 pneumonitis; permanently discontinue for Grade 3 or 4 pneumonitis.

In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, pneumonitis occurred in 5% of patients, including Grade 3 (0.8%), Grade 4 (<0.1%), and Grade 5 (0.3%) pneumonitis. Pneumonitis led to discontinuation of IMFINZI in 1.5% of the 1889 patients. The incidence of pneumonitis (including radiation pneumonitis) was higher in patients in the PACIFIC study who completed treatment with definitive chemoradiation within 42 days prior to initiation of IMFINZI (34%) compared to patients in other clinical studies (2.3%) in which radiation therapy was generally not administered immediately prior to initiation of IMFINZI. In the PACIFIC study, the incidence of Grade 3 pneumonitis was 3.4% and of Grade 5 pneumonitis was 1.1% in the IMFINZI arm. In the PACIFIC study, pneumonitis led to discontinuation of IMFINZI in 6% of patients.

The frequency and severity of immune-mediated pneumonitis were similar whether IMFINZI was given as a single agent in patients with various cancers or in combination with chemotherapy in patients with ES-SCLC.

Immune-Mediated Hepatitis

IMFINZI can cause immune-mediated hepatitis, defined as requiring use of corticosteroids. Fatal cases have been reported. Monitor patients for signs and symptoms of hepatitis during and after discontinuation of IMFINZI, including clinical chemistry monitoring. Administer corticosteroids for Grade 2 or higher elevations of ALT, AST, and/or total bilirubin. Withhold IMFINZI for ALT or AST greater than 3 but less than or equal to 8 times the ULN or total bilirubin greater than 1.5 but less than or equal to 5 times the ULN; permanently discontinue IMFINZI for ALT or AST greater than 8 times the ULN or total bilirubin greater than 5 times the ULN or concurrent ALT or AST greater than 3 times the ULN and total bilirubin greater than 2 times the ULN with no other cause.

In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, hepatitis occurred in 12% of patients, including Grade 3 (4.4%), Grade 4 (0.4%), and Grade 5 (0.2%) hepatitis. Hepatitis led to discontinuation of IMFINZI in 0.7% of the 1889 patients.

Immune-Mediated Colitis

IMFINZI can cause immune-mediated colitis, defined as requiring use of corticosteroids. Administer corticosteroids for Grade 2 or greater colitis or diarrhea. Withhold IMFINZI for Grade 2 colitis or diarrhea; permanently discontinue for Grade 3 or 4 colitis or diarrhea.

In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, colitis or diarrhea occurred in 18% of patients, including Grade 3 (1.0%) and Grade 4 (0.1%) immune-mediated colitis. Diarrhea or colitis led to discontinuation of IMFINZI in 0.4% of the 1889 patients.

Immune-Mediated Endocrinopathies

IMFINZI can cause immune-mediated endocrinopathies, including thyroid disorders, adrenal insufficiency, type 1 diabetes mellitus, and hypophysitis/hypopituitarism. Monitor patients for clinical signs and symptoms of endocrinopathies.

  • Thyroid disordersMonitor thyroid function prior to and periodically during treatment. Initiate hormone replacement therapy or medical management of hyperthyroidism as clinically indicated. Withhold IMFINZI for Grades 2–4 hyperthyroidism, until clinically stable. Continue IMFINZI for hypothyroidism.

    In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, hypothyroidism occurred in 11% of patients, while hyperthyroidism occurred in 7% of patients. Thyroiditis occurred in 0.9% of patients, including Grade 3 (<0.1%) thyroiditis. Hypothyroidism was preceded by thyroiditis or hyperthyroidism in 25% of patients.

  • Adrenal insufficiencyAdminister corticosteroids as clinically indicated and withhold IMFINZI until clinically stable for Grade 2 or higher adrenal insufficiency. In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, adrenal insufficiency occurred in 0.7% of patients, including Grade 3 (<0.1%) adrenal insufficiency.
  • Type 1 diabetes mellitusInitiate treatment with insulin as clinically indicated. Withhold IMFINZI for Grades 2–4 type 1 diabetes mellitus, until clinically stable. In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, type 1 diabetes mellitus occurred in <0.1% of patients.
  • HypophysitisAdminister corticosteroids and hormone replacement as clinically indicated and withhold IMFINZI until clinically stable for Grade 2 or higher hypophysitis. Hypopituitarism leading to adrenal insufficiency and diabetes insipidus occurred in <0.1% of 1889 patients with various cancers who received IMFINZI.

Immune-Mediated Nephritis

IMFINZI can cause immune-mediated nephritis, defined as evidence of renal dysfunction requiring use of corticosteroids. Fatal cases have occurred. Monitor patients for abnormal renal function tests prior to and periodically during treatment with IMFINZI. Administer corticosteroids as clinically indicated. Withhold IMFINZI for creatinine greater than 1.5 to 3 times the ULN; permanently discontinue IMFINZI and administer corticosteroids in patients with creatinine greater than 3 times the ULN.

In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, nephritis (reported as any of the following: increased creatinine or urea, acute kidney injury, renal failure, decreased glomerular filtration rate, tubulointerstitial nephritis, decreased creatinine clearance, glomerulonephritis, and nephritis) occurred in 6.3% of the patients including Grade 3 (1.1%), Grade 4 (0.2%), and Grade 5 (0.1%) nephritis. IMFINZI was discontinued in 0.3% of the 1889 patients.

Immune-Mediated Dermatologic Reactions

IMFINZI can cause immune-mediated rash. Stevens Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN) has occurred with other products in this class. Administer corticosteroids for Grade 2 rash or dermatitis lasting for more than 1 week or for Grade 3 or 4 rash or dermatitis. Withhold IMFINZI for Grade 2 rash or dermatitis lasting longer than 1 week or Grade 3 rash or dermatitis; permanently discontinue IMFINZI in patients with Grade 4 rash or dermatitis.

In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, 26% of patients developed rash or dermatitis and 0.4% of the patients developed vitiligo. Rash or dermatitis led to discontinuation of IMFINZI in 0.1% of the 1889 patients.

Other Immune-Mediated Adverse Reactions

IMFINZI can cause severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any organ system. While immune-mediated reactions usually manifest during treatment with IMFINZI, immune-mediated adverse reactions can also manifest after discontinuation of IMFINZI. For suspected immune-mediated adverse reactions, exclude other causes and initiate corticosteroids as clinically indicated. Withhold IMFINZI for Grade 3 immune-mediated adverse reactions, unless clinical judgment indicates discontinuation; permanently discontinue IMFINZI for Grade 4 adverse reactions.

The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in 1889 patients who received IMFINZI: aseptic meningitis, hemolytic anemia, immune thrombocytopenic purpura, myocarditis, myositis, and ocular inflammatory toxicity, including uveitis and keratitis. In patients who received IMFINZI in clinical studies outside of the pooled dataset, myasthenia gravis occurred at an incidence of less than 0.1%. Permanently discontinue IMFINZI if myasthenia gravis does not resolve to ≤ Grade 1 within 30 days or if there are signs of respiratory and/or autonomic insufficiency. Additional clinically significant immune-mediated adverse reactions have been seen with other products in this class (see Warnings and Precautions Section 5.7 of IMFINZI full Prescribing Information).

Infection

IMFINZI can cause serious infections, including fatal cases. Monitor patients for signs and symptoms of infection and treat as clinically indicated. Withhold IMFINZI for Grade 3 or 4 infection, until clinically stable.

In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, infections occurred in 43% of patients, including Grade 3 (8%), Grade 4 (1.9%), and Grade 5 (1.0%). The overall incidence of infections in IMFINZI-treated patients in the PACIFIC study (56%) was higher compared to patients in other clinical studies (38%) in which radiation therapy was generally not administered immediately prior to initiation of IMFINZI. In patients with UC in Study 1108 (n=182), the most common Grade 3 or higher infection was urinary tract infections, which occurred in 4% of patients. In patients with Stage III NSCLC in the PACIFIC study, the most common Grade 3 or higher infection was pneumonia, which occurred in 5% of patients.

Infusion-Related Reactions

IMFINZI can cause severe or life-threatening infusion-related reactions. Monitor patients for signs and symptoms of an infusion-related reaction. Interrupt or slow the rate of infusion for Grades 1–2 infusion-related reactions; permanently discontinue for Grades 3–4 infusion-related reactions.

In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, infusion-related reactions occurred in 2.2% of patients, including Grade 3 (0.3%).

Embryo-Fetal Toxicity

Based on its mechanism of action and data from animal studies, IMFINZI can cause fetal harm when administered to a pregnant woman. There are no data on the use of IMFINZI in pregnant women. Advise pregnant women of the potential risk to a fetus and advise women of reproductive potential to use effective contraception during treatment and for at least 3 months after the last dose of IMFINZI.

Lactation

There is no information regarding the presence of IMFINZI in human milk; however, because of the potential for adverse reactions in breastfed infants from IMFINZI, advise women not to breastfeed during treatment and for at least 3 months after the last dose.

Most Common Adverse Reactions

  • In patients with Stage III NSCLC in the PACIFIC study (IMFINZI n=475), the most common adverse reactions (≥20% of patients) were cough (40%), fatigue (34%), pneumonitis or radiation pneumonitis (34%), upper respiratory tract infections (26%), dyspnea (25%), and rash (23%). The most common Grade 3 or 4 adverse reactions (≥3%) were pneumonitis/radiation pneumonitis (3.4%) and pneumonia (7%)
  • In patients with Stage III NSCLC in the PACIFIC study (IMFINZI n=475), discontinuation due to adverse reactions occurred in 15% of patients in the IMFINZI arm. Serious adverse reactions occurred in 29% of patients receiving IMFINZI. The most frequent serious adverse reactions (≥2% of patients) were pneumonitis or radiation pneumonitis (7%) and pneumonia (6%). Fatal pneumonitis or radiation pneumonitis and fatal pneumonia occurred in <2% of patients and were similar across arms

The safety and effectiveness of IMFINZI have not been established in pediatric patients.

Indication

IMFINZI is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.

Please see complete Prescribing Information, including Medication Guide.

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