MARLIN

SAFETY

Please see the serious Warnings and Precautions associated with IMFINZI.

Immune-mediated Adverse Events

Adverse events reported among urothelial carcinoma patients treated with IMFINZI1

Immune-mediated adverse events reported among patients treated with IMFINZI™ (durvalumab)Immune-mediated adverse events reported among patients treated with IMFINZI™ (durvalumab)

  • Safety data are based on 182 patients who received IMFINZI 10 mg/kg Q2W for a median duration of exposure of 10.2 weeks1
  • 8 patients (4.4%) who were treated with IMFINZI experienced Grade 5 adverse events of cardiorespiratory arrest, general physical health deterioration, sepsis, ileus, pneumonitis, or immune-mediated hepatitis1
  • 3 additional patients were experiencing infection and disease progression at the time of death1
  • Serious adverse reactions occurred in 46% of patients1
  • The most frequent serious adverse reactions (>2%) were acute kidney injury (4.9%), urinary tract infection (4.4%), musculoskeletal pain (4.4%), liver injury (3.3%), general physical health deterioration (3.3%), sepsis (2.7%), abdominal pain (2.7%), and pyrexia/tumor associated fever (2.7%)1

*Includes upper abdominal pain, lower abdominal pain, and flank pain.

Includes asthenia, lethargy, and malaise.

Includes edema, localized edema, peripheral edema, lymphedema, peripheral swelling, scrotal edema, and scrotal swelling.

§Includes cystitis, candiduria, and urosepsis.

||Includes back pain, musculoskeletal chest pain, musculoskeletal pain and discomfort, myalgia, and neck pain.

Includes dermatitis, acneiform dermatitis, psoriasiform dermatitis, psoriasis, maculopapular rash, pruritic rash, papular rash, pustular rash, skin toxicity, eczema, erythema, erythema multiforme, erythematous rash, acne, and lichen planus.

 

Discontinuation Rate

Few discontinuations due to adverse events with IMFINZI1

Discontinuations due to adverse eventsDiscontinuations due to adverse events

 

Laboratory Abnormalities

Early identification and intervention may help manage many immune-mediated adverse events1

  • Immune-mediated adverse reactions requiring systemic corticosteroids or hormone replacement therapy occurred in 8.2% of patients1
    • – Including 5.5% of patients who required systemic corticosteroid therapy and 2.7% of patients who required only hormone replacement therapy1
  • 3.8% of patients received an oral prednisone dose equivalent to ≥40 mg daily for an immune-mediated adverse reaction1

Grade 3–4 laboratory abnormalities reported1

Reported laboratory abnormalies in patientsReported laboratory abnormalies in patients

ALT: alanine aminotransferase; AST: aspartate aminotransferase.

 
 

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

 

Help your patients monitor their treatment experience, including immune-mediated adverse events (imAEs), with Lighthouse

 

Learn more about how Lighthouse can help support your patients

Download now

 

Important Safety Information

There are no contraindications for IMFINZI™ (durvalumab).

Monitor patients for clinical signs and symptoms of immune-mediated pneumonitis, hepatitis, colitis or diarrhea, endocrinopathies, nephritis, rash or dermatitis, other immune-mediated adverse reactions, and infection. Please refer to the full Prescribing Information for important dose management information specific to adverse reactions.

immune-Mediated Pneumonitis

In the combined safety database (n=1414), immune-mediated pneumonitis occurred in 32 patients (2.3%), including 1 fatal case (0.1%) and 6 Grade 3–4 cases (0.4%). In Study 1 (n=182), 1 patient (0.5%) died from immune-mediated pneumonitis. Monitor patients for signs and symptoms of pneumonitis and evaluate with radiographic imaging when suspected. Administer corticosteroids for ≥Grade 2 pneumonitis. Withhold IMFINZI for Grade 2 pneumonitis; permanently discontinue for Grade 3–4 pneumonitis.

immune-Mediated Hepatitis

In the combined safety database (n=1414), immune-mediated hepatitis occurred in 16 patients (1.1%), including 1 fatal case (<0.1%) and 9 Grade 3 cases (0.6%). Grade 3–4 elevations in ALT occurred in 40/1342 patients (3.0%), AST in 58/1336 patients (4.3%), and total bilirubin in 37/1341 patients (2.8%). In Study 1 (n=182), 1 patient (0.5%) died from immune-mediated hepatitis, and 2 patients (1.1%) experienced immune-mediated hepatitis, including 1 Grade 3 case (0.5%). Monitor patients for abnormal liver tests in each cycle during treatment with IMFINZI. Administer corticosteroids and withhold IMFINZI for Grade 2–3 ALT or AST >3–5X ULN or ≤8X ULN or total bilirubin >1.5–3X ULN or ≤5X ULN. Permanently discontinue IMFINZI in patients with Grade 3 ALT or AST >8X ULN or total bilirubin >5X ULN, or in patients with concurrent ALT or AST >3X ULN and total bilirubin >2X ULN with no other cause.

immune-Mediated Colitis

In the combined safety database (n=1414), immune-mediated colitis or diarrhea occurred in 18 patients (1.3%), including 1 Grade 4 case (<0.1%) and 4 Grade 3 cases (0.3%). In Study 1 (n=182), 23 patients (12.6%) experienced colitis or diarrhea, including 2 Grade 3–4 cases (1.1%). Monitor patients for signs and symptoms of colitis or diarrhea. Administer corticosteroids for ≥Grade 2 colitis or diarrhea. Withhold IMFINZI for Grade 2 colitis or diarrhea; permanently discontinue for Grade 3–4 colitis or diarrhea.

immune-Mediated Endocrinopathies

  • Immune-mediated thyroid disorders, adrenal insufficiency, type 1 diabetes mellitus and hypophysitis/hypopituitarism have occurred with IMFINZI. Monitor patients for clinical signs and symptoms of endocrinopathies. For Grade 2–4 endocrinopathies (except hypothyroidism) withhold dose until clinically stable and offer symptomatic management for hyperthyroidism. For Grade 2–4 hypothyroidism, initiate thyroid hormone replacement as needed
  • Thyroid disorders—In the combined safety database (n=1414), immune-mediated hypothyroidism and hyperthyroidism occurred in 136 patients (9.6%) and 81 patients (5.7%), respectively. Thyroiditis occurred in 10 patients (0.7%), including 1 Grade 3 case (<0.1%) in a patient who had a myocardial infarction. In 9 patients with thyroiditis, transient hyperthyroidism preceded hypothyroidism. Treatment with a beta-blocker and/or thioamide was administered for hyperthyroidism in five of these patients. In Study 1 (n=182), Grade 1–2 hypothyroidism or thyroiditis occurred in 10 patients (5.5%). Grade 1–2 hyperthyroidism or thyroiditis leading to hyperthyroidism occurred in 9 patients (4.9%). Monitor patients for abnormal thyroid function tests prior to and periodically during treatment
  • Immune-mediated adrenal insufficiency—In the combined safety database (n=1414), immune-mediated adrenal insufficiency occurred in 13 patients (0.9%), including 2 Grade 3 cases (0.1%). In Study 1 (n=182), Grade 1 adrenal insufficiency occurred in 1 patient (0.5%). Administer corticosteroids and hormone replacement as clinically indicated
  • Type 1 diabetes mellitus—In the combined safety database (n=1414), new onset type 1 diabetes mellitus without an alternative etiology occurred in 1 patient (<0.1%). For type 1 diabetes mellitus, initiate insulin as indicated and withhold IMFINZI until clinically stable
  • Hypophysitis—In the combined safety database (n=1414), hypopituitarism leading to adrenal insufficiency and diabetes insipidus occurred in 1 patient (<0.1%). Administer corticosteroids and hormone replacement as clinically indicated

Other immune-Mediated Adverse Reactions

  • IMFINZI has caused immune-mediated rash. Other immune-related adverse reactions, including aseptic meningitis, hemolytic anemia, immune thrombocytopenic purpura, myocarditis, myositis, nephritis, and ocular inflammatory toxicity including uveitis and keratitis, have occurred in ≤1.0% of patients treated with IMFINZI
  • Immune-mediated rash or dermatitis—In the combined safety database (n=1414), immune-mediated rash or dermatitis occurred in 220 patients (15.6%) and 4 patients (0.3%) developed vitiligo. In Study 1 (n=182), 20 patients (11.0%) developed rash, including 1 Grade 3 case (0.5%). Patients should be monitored for signs and symptoms of rash or dermatitis. Administer corticosteroids if indicated. Withhold IMFINZI for Grade 3 rash or dermatitis or Grade 2 rash or dermatitis lasting >1 week. Permanently discontinue IMFINZI in patients with Grade 4 rash or dermatitis
  • Immune thrombocytopenic purpura—In the combined safety database (n=1414), 1 fatal case (<0.1%) of immune thrombocytopenic purpura occurred. Monitor patients for signs and symptoms of immune thrombocytopenic purpura
  • Nephritis—In the combined safety database (n=1414), immune-mediated nephritis occurred in 3 patients (0.2%), including 2 Grade 3 cases (0.1%). Monitor patients for abnormal renal function tests prior to and during each cycle of IMFINZI. Administer corticosteroids for ≥Grade 2 nephritis (creatinine >1.5X ULN). Withhold IMFINZI for Grade 2 nephritis; permanently discontinue for ≥Grade 3 nephritis (creatinine >3X ULN)

Infection

Severe infections, including sepsis, necrotizing fasciitis, and osteomyelitis, occurred in patients receiving IMFINZI. In the combined safety database (n=1414), infections occurred in 531 patients (37.6%). In Study 1 (n=182), infections occurred in 54 patients (29.7%). 11 patients (6.0%) experienced Grade 3–4 infection and 5 patients (2.7%) were experiencing infection at the time of death. 8 patients (4.4%) experienced urinary tract infection, the most common ≥Grade 3 infection. Monitor patients for signs and symptoms of infection and treat with anti-infectives for suspected or confirmed infections. Withhold IMFINZI for ≥Grade 3 infection.

Infusion-Related Reactions

In the combined safety database (n=1414), severe infusion-related reactions occurred in 26 patients (1.8%). In Study 1 (n=182), infusion-related reactions occurred in 3 patients (1.6%). There were 5 Grade 3 (0.4%) and no Grade 4 or 5 reactions. Patients should be monitored for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1–2 infusion-related reactions and permanently discontinue for Grade 3–4 infusion-related reactions.

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.

Nursing Mothers

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 a lactating woman not to breastfeed during treatment and for at least 3 months after the last dose.

Most Common Adverse Reactions

  • The most common adverse reactions (≥15%) were fatigue (39%), musculoskeletal pain (24%), constipation (21%), decreased appetite (19%), nausea (16%), peripheral edema (15%), and urinary tract infection (15%). The most common Grade 3 or 4 adverse reactions (≥3%) were fatigue, urinary tract infection, musculoskeletal pain, abdominal pain, dehydration, and general physical health deterioration
  • Adverse reactions leading to discontinuation of IMFINZI occurred in 3.3% of patients. Serious adverse reactions occurred in 46% of patients. The most frequent serious adverse reactions (>2%) were acute kidney injury (4.9%), urinary tract infection (4.4%), musculoskeletal pain (4.4%), liver injury (3.3%), general physical health deterioration (3.3%), sepsis, abdominal pain, and pyrexia/tumor associated fever (2.7% each)

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

Indication

IMFINZI is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who:

  • have disease progression during or following platinum-containing chemotherapy
  • have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Please see complete Prescribing Information including Patient Information.

Reference: 1. IMFINZI [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.

Important Safety Information +

There are no contraindications for IMFINZI™ (durvalumab).

Monitor patients for clinical signs and symptoms of immune-mediated pneumonitis, hepatitis, colitis or diarrhea, endocrinopathies, nephritis, rash or dermatitis, other immune-mediated adverse reactions, and infection.

Important Safety Information +

There are no contraindications for IMFINZI™ (durvalumab).

Monitor patients for clinical signs and symptoms of immune-mediated pneumonitis, hepatitis, colitis or diarrhea, endocrinopathies, nephritis, rash or dermatitis, other immune-mediated adverse reactions, and infection. Please refer to the full Prescribing Information for important dose management information specific to adverse reactions.

immune-mediated Pneumonitis

In the combined safety database (n=1414), immune-mediated pneumonitis occurred in 32 patients (2.3%), including 1 fatal case (0.1%) and 6 Grade 3–4 cases (0.4%). In Study 1 (n=182), 1 patient (0.5%) died from immune-mediated pneumonitis. Monitor patients for signs and symptoms of pneumonitis and evaluate with radiographic imaging when suspected. Administer corticosteroids for ≥Grade 2 pneumonitis. Withhold IMFINZI for Grade 2 pneumonitis; permanently discontinue for Grade 3–4 pneumonitis.

immune-mediated Hepatitis

In the combined safety database (n=1414), immune-mediated hepatitis occurred in 16 patients (1.1%), including 1 fatal case (<0.1%) and 9 Grade 3 cases (0.6%). Grade 3–4 elevations in ALT occurred in 40/1342 patients (3.0%), AST in 58/1336 patients (4.3%), and total bilirubin in 37/1341 patients (2.8%). In Study 1 (n=182), 1 patient (0.5%) died from immune-mediated hepatitis, and 2 patients (1.1%) experienced immune-mediated hepatitis, including 1 Grade 3 case (0.5%). Monitor patients for abnormal liver tests in each cycle during treatment with IMFINZI. Administer corticosteroids and withhold IMFINZI for Grade 2–3 ALT or AST >3–5X ULN or ≤8X ULN or total bilirubin >1.5–3X ULN or ≤5X ULN. Permanently discontinue IMFINZI in patients with Grade 3 ALT or AST >8X ULN or total bilirubin >5X ULN, or in patients with concurrent ALT or AST >3X ULN and total bilirubin >2X ULN with no other cause.

immune-mediated Colitis

In the combined safety database (n=1414), immune-mediated colitis or diarrhea occurred in 18 patients (1.3%), including 1 Grade 4 case (<0.1%) and 4 Grade 3 cases (0.3%). In Study 1 (n=182), 23 patients (12.6%) experienced colitis or diarrhea, including 2 Grade 3–4 cases (1.1%). Monitor patients for signs and symptoms of colitis or diarrhea. Administer corticosteroids for ≥Grade 2 colitis or diarrhea. Withhold IMFINZI for Grade 2 colitis or diarrhea; permanently discontinue for Grade 3–4 colitis or diarrhea.

immune-mediated Endocrinopathies

  • Immune-mediated thyroid disorders, adrenal insufficiency, type 1 diabetes mellitus and hypophysitis/hypopituitarism have occurred with IMFINZI. Monitor patients for clinical signs and symptoms of endocrinopathies. For Grade 2–4 endocrinopathies (except hypothyroidism) withhold dose until clinically stable and offer symptomatic management for hyperthyroidism. For Grade 2–4 hypothyroidism, initiate thyroid hormone replacement as needed
  • Thyroid disorders—In the combined safety database (n=1414), immune-mediated hypothyroidism and hyperthyroidism occurred in 136 patients (9.6%) and 81 patients (5.7%), respectively. Thyroiditis occurred in 10 patients (0.7%), including 1 Grade 3 case (<0.1%) in a patient who had a myocardial infarction. In 9 patients with thyroiditis, transient hyperthyroidism preceded hypothyroidism. Treatment with a beta-blocker and/or thioamide was administered for hyperthyroidism in five of these patients. In Study 1 (n=182), Grade 1–2 hypothyroidism or thyroiditis occurred in 10 patients (5.5%). Grade 1–2 hyperthyroidism or thyroiditis leading to hyperthyroidism occurred in 9 patients (4.9%). Monitor patients for abnormal thyroid function tests prior to and periodically during treatment
  • Immune-mediated adrenal insufficiency—In the combined safety database (n=1414), immune-mediated adrenal insufficiency occurred in 13 patients (0.9%), including 2 Grade 3 cases (0.1%). In Study 1 (n=182), Grade 1 adrenal insufficiency occurred in 1 patient (0.5%). Administer corticosteroids and hormone replacement as clinically indicated
  • Type 1 diabetes mellitus—In the combined safety database (n=1414), new onset type 1 diabetes mellitus without an alternative etiology occurred in 1 patient (<0.1%). For type 1 diabetes mellitus, initiate insulin as indicated and withhold IMFINZI until clinically stable
  • Hypophysitis—In the combined safety database (n=1414), hypopituitarism leading to adrenal insufficiency and diabetes insipidus occurred in 1 patient (<0.1%). Administer corticosteroids and hormone replacement as clinically indicated

Other immune-mediated Adverse Reactions

  • IMFINZI has caused immune-mediated rash. Other immune-related adverse reactions, including aseptic meningitis, hemolytic anemia, immune thrombocytopenic purpura, myocarditis, myositis, nephritis, and ocular inflammatory toxicity including uveitis and keratitis, have occurred in ≤1.0% of patients treated with IMFINZI
  • Immune-mediated rash or dermatitis—In the combined safety database (n=1414), immune-mediated rash or dermatitis occurred in 220 patients (15.6%) and 4 patients (0.3%) developed vitiligo. In Study 1 (n=182), 20 patients (11.0%) developed rash, including 1 Grade 3 case (0.5%). Patients should be monitored for signs and symptoms of rash or dermatitis. Administer corticosteroids if indicated. Withhold IMFINZI for Grade 3 rash or dermatitis or Grade 2 rash or dermatitis lasting >1 week. Permanently discontinue IMFINZI in patients with Grade 4 rash or dermatitis
  • Immune thrombocytopenic purpura—In the combined safety database (n=1414), 1 fatal case (<0.1%) of immune thrombocytopenic purpura occurred. Monitor patients for signs and symptoms of immune thrombocytopenic purpura
  • Nephritis—In the combined safety database (n=1414), immune-mediated nephritis occurred in 3 patients (0.2%), including 2 Grade 3 cases (0.1%). Monitor patients for abnormal renal function tests prior to and during each cycle of IMFINZI. Administer corticosteroids for ≥Grade 2 nephritis (creatinine >1.5X ULN). Withhold IMFINZI for Grade 2 nephritis; permanently discontinue for ≥Grade 3 nephritis (creatinine >3X ULN)

Infection

Severe infections, including sepsis, necrotizing fasciitis, and osteomyelitis, occurred in patients receiving IMFINZI. In the combined safety database (n=1414), infections occurred in 531 patients (37.6%). In Study 1 (n=182), infections occurred in 54 patients (29.7%). 11 patients (6.0%) experienced Grade 3–4 infection and 5 patients (2.7%) were experiencing infection at the time of death. 8 patients (4.4%) experienced urinary tract infection, the most common ≥Grade 3 infection. Monitor patients for signs and symptoms of infection and treat with anti-infectives for suspected or confirmed infections. Withhold IMFINZI for ≥Grade 3 infection.

Infusion-Related Reactions

In the combined safety database (n=1414), severe infusion-related reactions occurred in 26 patients (1.8%). In Study 1 (n=182), infusion-related reactions occurred in 3 patients (1.6%). There were 5 Grade 3 (0.4%) and no Grade 4 or 5 reactions. Patients should be monitored for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1–2 infusion-related reactions and permanently discontinue for Grade 3–4 infusion-related reactions.

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.

Nursing Mothers

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 a lactating woman not to breastfeed during treatment and for at least 3 months after the last dose.

Most Common Adverse Reactions

  • The most common adverse reactions (≥15%) were fatigue (39%), musculoskeletal pain (24%), constipation (21%), decreased appetite (19%), nausea (16%), peripheral edema (15%), and urinary tract infection (15%). The most common Grade 3 or 4 adverse reactions (≥3%) were fatigue, urinary tract infection, musculoskeletal pain, abdominal pain, dehydration, and general physical health deterioration
  • Adverse reactions leading to discontinuation of IMFINZI occurred in 3.3% of patients. Serious adverse reactions occurred in 46% of patients. The most frequent serious adverse reactions (>2%) were acute kidney injury (4.9%), urinary tract infection (4.4%), musculoskeletal pain (4.4%), liver injury (3.3%), general physical health deterioration (3.3%), sepsis, abdominal pain, and pyrexia/tumor associated fever (2.7% each)

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

Indication

IMFINZI is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who:

  • have disease progression during or following platinum-containing chemotherapy
  • have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Please see complete Prescribing Information including Patient Information.

Top