Medical Editor: John P. Cunha, DO, FACOEP
What Is Imfinzi?
Imfinzi (durvalumab) is a programmed death-ligand 1 (PD-L1) blocking antibody indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy; or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
What Are Side Effects of Imfinzi?
Common side effects of Imfinzi include:
- musculoskeletal pain,
- decreased appetite,
- swelling of extremities,
- urinary tract infection,
- abdominal pain,
- shortness of breath,
- cough, and
Dosage for Imfinzi
Administer Imfinzi in a dose of 10 mg/kg as an intravenous infusion over 60 minutes every 2 weeks.
What Drugs, Substances, or Supplements Interact with Imfinzi?
Imfinzi may interact with other drugs. Tell your doctor all medications and supplements you use.
Imfinzi During Pregnancy and Breastfeeding
Imfinzi is not recommended for use during pregnancy; it may harm a fetus. Females of reproductive are advised to use effective contraception during treatment with Imfinzi, and for at least 3 months following the last dose. It is unknown if Imfinzi passes into breast milk. Because of the potential for adverse reactions in breastfed infants, women are advised not to breastfeed during treatment with Imfinzi and for at least 3 months after the last dose.z
Our Imfinzi (durvalumab) Injection Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
The following adverse reactions are discussed in greater detail in other sections of the labeling.
- Immune-Mediated Pneumonitis [see WARNINGS AND PRECAUTIONS].
- Immune-Mediated Hepatitis [see WARNINGS AND PRECAUTIONS].
- Immune-Mediated Colitis [see WARNINGS AND PRECAUTIONS].
- Immune-Mediated Endocrinopathies [see WARNINGS AND PRECAUTIONS].
- Immune-Mediated Nephritis [see WARNINGS AND PRECAUTIONS].
- Immune-Mediated Dermatologic Reactions [see WARNINGS AND PRECAUTIONS].
- Other Immune-Mediated Adverse Reactions [see WARNINGS AND PRECAUTIONS].
- Infection [see WARNINGS AND PRECAUTIONS].
- Infusion-Related Reactions [see WARNINGS AND PRECAUTIONS].
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described in the Warnings and Precautions section reflect exposure to IMFINZI in 1889 patients from the PACIFIC study (a randomized, placebo-controlled study that enrolled 475 patients with Stage III NSCLC), Study 1108 (an open-label, single-arm, multicohort study that enrolled 191 patients with urothelial carcinoma and 779 patients with other solid tumors), and additional open-label, single-arm trial that enrolled 444 patients with metastatic lung cancer, an indication for which durvalumab is not approved. In these trials, IMFINZI was administered at a dose of 10 mg/kg every 2 weeks. Among the 1889 patients, 38% were exposed for 6 months or more and 18% were exposed for 12 months or more. The data also reflects exposure to IMFINZI in combination with chemotherapy in 265 patients from the CASPIAN study (a randomized, open-label study in patients with ES-SCLC). In the CASPIAN study, IMFINZI was administered at a dose of 1500 mg every 3 or 4 weeks.
The data described in this section reflect exposure to IMFINZI in patients with locally advanced or metastatic urothelial carcinoma enrolled in Study 1108, in patients with Stage III NSCLC enrolled in the PACIFIC study and in patients with ES-SCLC enrolled in the CASPIAN study.
The safety of IMFINZI was evaluated in 182 patients with locally advanced or metastatic urothelial carcinoma in the urothelial carcinoma cohort of Study 1108 whose disease has progressed during or after one standard platinum-based regimen. Patients received IMFINZI 10 mg/kg intravenously every 2 weeks [see Clinical Studies]. The median duration of exposure was 2.3 months (range: 1 day to 12.1 months).
Thirty-one percent (31%) of patients had a drug delay or interruption for an adverse reaction. The most common (> 2%) were liver injury (4.9%), urinary tract infection (3.3%), acute kidney injury (3.3%), and musculoskeletal pain (2.7%).
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.
Eight patients (4.4%) who were treated with IMFINZI experienced Grade 5 adverse reactions of cardiorespiratory arrest, general physical health deterioration, sepsis, ileus, pneumonitis, or immune-mediated hepatitis. Three additional patients were experiencing infection and disease progression at the time of death. IMFINZI was discontinued for adverse reactions 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).
Table 3 summarizes the adverse reactions that occurred in ≥ 10% of patients, while Table 4 summarizes the Grade 3 -4 laboratory abnormalities that occurred in ≥ 1% of patients treated with IMFINZI in the urothelial carcinoma cohort of Study 1108.
Table 3. Adverse Reactions in ≥ 10% of Patients in Study 1108 Urothelial Carcinoma Cohort
N = 182
|Grades 3 -4|
|General Disorders and Administration|
|Pyrexia/Tumor associated fever||14||0.5|
|Urinary tract infection4||15||4.4|
|Metabolism and Nutrition Disorders|
|Musculoskeletal and Connective Tissue Disorders|
|Respiratory, Thoracic, and Mediastinal Disorders|
|Skin and Subcutaneous Tissue Disorders|
|1 Includes abdominal pain upper, abdominal pain lower, and flank pain|
2 Includes asthenia, lethargy, and malaise
3 Includes edema, localized edema, edema peripheral, lymphedema, peripheral swelling, scrotal edema, and scrotal swelling
4 Includes cystitis, candiduria, and urosepsis
5 Includes back pain, musculoskeletal chest pain, musculoskeletal pain and discomfort, myalgia, and neck pain
6 Includes dermatitis, dermatitis acneiform, dermatitis psoriasiform, psoriasis, rash maculo-papular, rash pruritic, rash papular, rash pustular, skin toxicity, eczema, erythema, erythema multiforme, rash erythematous, acne, and lichen planus
Table 4. Grade 3-4 Laboratory Abnormalities Worsened from Baseline Occurring in ≥ 1% Patients in Study 1108 Urothelial Carcinoma Cohort
|Laboratory Abnormality||Grades 3 -4|
|Increased alkaline phosphatase||4.1|
Non-Small Cell Lung Cancer
The safety of IMFINZI in patients with Stage III NSCLC who completed concurrent platinum-based chemoradiotherapy within 42 days prior to initiation of study drug was evaluated in the PACIFIC study, a multicenter, randomized, double-blind, placebo-controlled study. A total of 475 patients received IMFINZI 10 mg/kg intravenously every 2 weeks. The study excluded patients who had disease progression following chemoradiation, with active or prior autoimmune disease within 2 years of initiation of the study or with medical conditions that required systemic immunosuppression [see Clinical Studies].
The study population characteristics were: median age of 64 years (range: 23 to 90), 45% age 65 years or older, 70% male, 69% White, 27% Asian, 75% former smoker, 16% current smoker, and 51% had WHO performance status of 1. All patients received definitive radiotherapy as per protocol, of which 92% received a total radiation dose of 54 Gy to 66 Gy. The median duration of exposure to IMFINZI was 10 months (range: 0.2 to 12.6).
IMFINZI was discontinued due to adverse reactions in 15% of patients. The most common adverse reactions leading to IMFINZI discontinuation were pneumonitis or radiation pneumonitis in 6% of patients. Serious adverse reactions occurred in 29% of patients receiving IMFINZI. The most frequent serious adverse reactions reported in at least 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 most common adverse reactions (occurring in ≥ 20% of patients) were cough, fatigue, pneumonitis or radiation pneumonitis, upper respiratory tract infections, dyspnea, and rash.
Table 5 summarizes the adverse reactions that occurred in at least 10% of patients treated with IMFINZI.
Table 5. Adverse Reactions Occurring in ≥ 10% Patients in the PACIFIC Study
N = 475
N = 234
|Respiratory, Thoracic, and Mediastinal Disorders|
|Skin and Subcutaneous Tissue Disorders|
|Upper respiratory tract infections9||26||0.4||19||0|
|1 The PACIFIC study was not designed to demonstrate statistically significant difference in adverse reaction rates for IMFINZI, as compared to placebo, for any specific adverse reaction listed in Table 4|
2 Includes acute interstitial pneumonitis, interstitial lung disease, pneumonitis, pulmonary fibrosis
3 Includes dyspnea, and exertional dyspnea
4 Includes abdominal pain, abdominal pain lower, abdominal pain upper, and flank pain
5 Includes autoimmune hypothyroidism and hypothyroidism
6 Includes rash erythematous, rash generalized, rash macular, rash maculopapular, rash papular, rash pruritic, rash pustular, erythema, eczema, rash, and dermatitis
7 Includes pruritus generalized and pruritus
8 Includes asthenia and fatigue
9 Includes laryngitis, nasopharyngitis, peritonsillar abscess, pharyngitis, rhinitis, sinusitis, tonsillitis, tracheobronchitis, and upper respiratory tract infection
10 Includes lung infection, pneumocystis jirovecii pneumonia, pneumonia, pneumonia adenoviral, pneumonia bacterial, pneumonia cytomegaloviral, pneumonia haemophilus, pneumonia klebsiella, pneumonia necrotising, pneumonia pneumococcal, and pneumonia streptococcal
Other adverse reactions occurring in less than 10% of patients treated with IMFINZI were dysphonia, dysuria, night sweats, peripheral edema, and increased susceptibility to infections.
Table 6 summarizes the laboratory abnormalities that occurred in at least 20% of patients treated with IMFINZI.
Table 6. Laboratory Abnormalities Worsening from Baseline Occurring in ≥ 20% of Patients in the PACIFIC Study
|Grade 3 or 4|
|Grade 3 or 4|
|1 Graded according to NCI CTCAE version 4.0|
2 Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: IMFINZI (range: 464 to 470) and placebo (range: 224 to 228)
Small Cell Lung Cancer
The safety of IMFINZI in combination with etoposide and either carboplatin or cisplatin in previously untreated ES-SCLC was evaluated in CASPIAN, a randomized, open-label, multicenter, active-controlled trial. A total of 265 patients received IMFINZI 1500 mg in combination with chemotherapy every 3 weeks for 4 cycles followed by IMFINZI 1500 mg every 4 weeks until disease progression or unacceptable toxicity. The trial excluded patients with active or prior autoimmune disease or with medical conditions that required systemic corticosteroids or immunosuppressants [see Clinical Studies]. Among 265 patients receiving IMFINZI, 49% were exposed for 6 months or longer and 19% were exposed for 12 months or longer.
Among 266 patients receiving chemotherapy alone, 57% of the patients received 6 cycles of chemotherapy and 8% of the patients received PCI after chemotherapy.
IMFINZI was discontinued due to adverse reactions in 7% of the patients receiving IMFINZI plus chemotherapy. These include pneumonitis, hepatotoxicity, neurotoxicity, sepsis, diabetic ketoacidosis and pancytopenia (1 patient each). Serious adverse reactions occurred in 31% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 1% of patients were febrile neutropenia (4.5%), pneumonia (2.3%), anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%) and COPD (1.1%). Fatal adverse reactions occurred in 4.9% of patients receiving IMFINZI plus chemotherapy. These include pancytopenia, sepsis, septic shock, pulmonary artery thrombosis, pulmonary embolism, and hepatitis (1 patient each) and sudden death (2 patients). The most common adverse reactions (occurring in ≥ 20% of patients) were nausea, fatigue/asthenia and alopecia.
Table 7 summarizes the adverse reactions that occurred in patients treated with IMFINZI plus chemotherapy.
Table 7. Adverse Reactions Occurring in ≥ 10% Patients in the CASPIAN study
|IMFINZI with etoposide and either carboplatin or cisplatin|
N = 265
|Etoposide and either carboplatin or cisplatin|
N = 266
|Adverse Reaction||All Grades (%)||Grade 3-4 (%)||All Grades (%)||Grade 3-4 (%)|
|Respiratory, thoracic and mediastinal disorders|
|Skin and subcutaneous tissue disorders|
|General disorders and administration site conditions|
|Metabolism and nutrition disorders|
|a Includes hyperthyroidism and Basedow's disease|
b Includes rash erythematous, rash generalized, rash macular, rash maculopapular, rash papular, rash pruritic, rash pustular, erythema, eczema, rash and dermatitis
Table 8 summarizes the laboratory abnormalities that occurred in at least 20% of patients treated with IMFINZI plus chemotherapy.
Table 8. Laboratory Abnormalities Worsening from Baseline Occurring in ≥ 20%1 of Patients in the CASPIAN study
|IMFINZI with Etoposide and either Carboplatin or Cisplatin||Etoposide and either Carboplatin or Cisplatin|
|Laboratory Abnormality||Grade2 3 or 4 (%)3||Grade2 3 or 4 (%)3|
|Increased Alkaline Phosphatase||4.9||3.5|
|Blood creatinine increased||3.4||1.1|
|TSH decreased < LLN4 and ≥ LLN at baseline||NA||NA|
|1 The frequency cut off is based on any grade change from baseline|
2 Graded according to NCI CTCAE version 4.03
3 Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: IMFINZI (range: 258 to 263) and chemotherapy (range: 253 to 262) except magnesium IMFINZI + chemotherapy (18) and chemotherapy (16)
4 LLN = lower limit of normal
As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to durvalumab to the incidence of antibodies to other products may be misleading.
Of 2280 patients who received IMFINZI 10 mg/kg every 2 weeks or 20 mg/kg every 4 weeks as a single-agent, 69 patients (3%) tested positive for treatment-emergent anti-drug antibodies (ADA) and 12 (0.5%) tested positive for neutralizing antibodies. The development of ADA against durvalumab appears to have no clinically relevant effect on its pharmacokinetics or safety.
Of 201 patients in the CASPIAN study who received IMFINZI 1500 mg every 3 weeks in combination with chemotherapy for four doses followed by IMFINZI 1500 mg every 4 weeks no patients tested positive for treatment-emergent ADA.
Read the entire FDA prescribing information for Imfinzi (Durvalumab Injection)