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EFFICACY

NEW APPROVAL

Overall Survival in ES-SCLC

INTERIM ANALYSIS: Half of patients were still alive at 13 months with IMFINZI + EP1,2*

Superior overall survival in first-line ES-SCLC
(median duration of follow-up 14.2 months)1,2

 

UPDATED ANALYSIS: OVERALL SURVIVAL RESULTS WITH >2 YEARS OF MEDIAN FOLLOW-UP3

Consistent overall survival at updated analysis
(median duration of follow-up 25.1 months)3†

 

  • OS rate at 18 months was a secondary endpoint2
  • At the time of updated analysis, mOS was 12.9 months (95% CI, 11.3-14.7) with IMFINZI + EP vs 10.5 months (95% CI, 9.3-11.2) with EP alone3

*Overall survival was the primary endpoint. At the time of the planned interim overall survival analysis with a median duration of follow-up of 14.2 months, mOS was 13 months (95% CI, 11.5-14.8) with IMFINZI + EP vs 10.3 months (95% CI, 9.3-11.2) with EP alone (HR=0.73; 95% CI, 0.59-0.91; P=0.0047).1,2

†The updated OS analysis was conducted with a median duration of follow-up of 25.1 months. OS rates at 12, 18, and 24 months are the estimated proportion of patients alive based on the updated analysis.3

Months matter in ES-SCLC—Start with IMFINZI + EP for all eligible patients1

UPDATED ANALYSIS: Overall survival demonstrated across patient subgroups with IMFINZI + EP3||

Prespecified subgroup overall survival analysis3

 

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IMFINZI + EP was evaluated in key patient subgroups reflective of clinical practice in ES-SCLC2,4-8

  • Patients over 65
  • Former and active smokers
  • Patients with brain/CNS metastases
  • Cisplatin- and carboplatin-eligible patients

ES-SCLC=extensive-stage small cell lung cancer; EP=etoposide and either carboplatin or cisplatin; mOS=median overall survival; HR=hazard ratio; CI=confidence interval; OS=overall survival; ECOG=Eastern Cooperative Oncology Group; WHO=World Health Organization; PS=performance status; CNS=central nervous system; AJCC=American Joint Committee on Cancer.

||OS subgroup analysis was not powered to show a statistically significant difference between or within individual subgroups.2

 

Progression-Free Survival in ES-SCLC

INTERIM ANALYSIS: At 1 year, 18% of patients were progression free with IMFINZI + EP2

Percentage of patients alive and progression free at 1 year
(median duration of follow-up 14.2 months)2

 

  • Median PFS: 5.1 months (95% CI, 4.7-6.2) with IMFINZI + EP and 5.4 months (95% CI, 4.8-6.2) with EP alone (HR=0.78; 95% CI, 0.65-0.94; 96% of total planned events)1
  • PFS was not formally tested for statistical significance at the interim analysis2
  • PFS rate at 12 months was a secondary endpoint2

UPDATED ANALYSIS: Landmark progression-free survival data for IMFINZI + EP with >2 years of median follow-up3

Progression-free survival with IMFINZI + EP and EP alone
(median duration of follow-up 25.1 months)3*

 

  • Median PFS did not change at the updated analysis1,3
  • PFS was not formally tested for statistical significance at the updated analysis3
  • PFS rate at 12 months was a secondary endpoint2

PFS=progression-free survival.

*PFS rates at 12, 18, and 24 months are the estimated proportion of patients alive and progression free based on the updated analysis.3

Objective Response Rate in ES-SCLC

INTERIM ANALYSIS: IMFINZI + EP provided a high response rate1,2

Confirmed objective response rate in first-line ES-SCLC (post-hoc analysis)1,2

 

  • Complete responses: 2% with IMFINZI + EP and 1% with EP alone2
  • Partial responses: 66% with IMFINZI + EP and 57% with EP alone2

Study Design and Patient Characteristics in ES-SCLC

The Phase III CASPIAN study compared IMFINZI + EP against real-world treatment with EP in ES-SCLC2,5

A large, randomized, open-label, multicenter study of IMFINZI + etoposide and platinum-based chemotherapy (EP) vs EP alone1,2

Phase III CASPIAN study design^IMFINZI + tremelimumab + EP arm failed to reach its primary endpoint.

Primary endpoint1,2

Overall survival

Key secondary endpoints1,2

  • PFS§
  • ORR (unconfirmed)§
  • OS at 18 months
  • PFS at 6 and 12 months
  • HRQoL patient-reported outcomes
CASPIAN allowed for

Investigator’s choice of platinum-based chemotherapy2||

Patients with asymptomatic or treated brain metastases

Patients with asymptomatic or treated brain metastases2¶

The control arm allowed for

Up to 6 cycles of EP 57% of patients received 6 cycles1

PCI per investigator’s discretion1

Baseline patient characteristics were well balanced between the IMFINZI + EP and EP arms2

Patient characteristics3

 

  IMFINZI + EP
(n=268)		 EP alone
(n=269)
Median age (years) (range) 62 (28-82) 62 (35-82)
Male, % 70.9 68.4
Race, %    
White 85.4 82.2
Asian 13.4 15.6
Other 1.1 2.2
WHO PS, %
0 36.9 33.5
1 63.1 66.5
Disease stage, %
III 10.4 8.9
IV 89.6 91.1
Smoking history, %
Current smoker/former smoker 44.8 46.8
Former smoker 47.0 47.6
Never smoker 8.2 5.6
Brain or CNS metastases, % 10.4 10.0
Liver metastases, % 40.3 38.7

*All patient's were confirmed as having ES-SCLC.

Q3W=once every 3 weeks; Q4W=once every 4 weeks; PCI=prophylactic cranial irradiation; ORR=objective response rate; HRQoL=health-related quality of life; PD-L1=programmed death-ligand 1; AUC=area under the curve; RECIST=Response Evaluation Criteria in Solid Tumors; CT=computed tomography; MRI=magnetic resonance imaging.

*IMFINZI 1500 mg + either carboplatin (AUC 5 mg/mL/min or 6 mg/mL/min) or cisplatin (75 mg/m2-80 mg/m2) on Day 1 and etoposide (80 mg/m2-100 mg/m2) intravenously on Days 1, 2, and 3 of each 21-day cycle for 4 cycles, followed by IMFINZI 1500 mg every 4 weeks until disease progression or unacceptable toxicity.1,2

†Either carboplatin (AUC 5 mg/mL/min or 6 mg/mL/min) or cisplatin (75 mg/m2-80 mg/m2) on Day 1 and etoposide (80 mg/m2-100 mg/m2) intravenously on Days 1, 2, and 3 of each 21-day cycle for 4 to 6 cycles.1,2

‡8% of patients who were treated with EP alone received PCI post-EP.1,2

§Assessed using investigator assessments according to RECIST v1.1.2

||78% received carboplatin and 25% received cisplatin in the IMFINZI + EP arm; 78% received carboplatin and 25% received cisplatin in the EP alone arm.2

Patients with confirmed brain metastases had to be treated and stable off steroids and anticonvulsants for at least 1 month prior to study treatment. Patients with suspected brain metastases at screening should have a CT/MRI of the brain prior to study entry.2

References: 1. IMFINZI SmPC, September 2020. 2. Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum–etoposide versus platinum–etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394(10212):1929-1939. 3. Paz-Ares LG, Dvorkin M, Chen Y, et al. Durvalumab ± tremelimumab + platinumetoposide in first-line extensive-stage SCLC: Updated results from the phase 3 CASPIAN study. J Clin Oncol. 2020;38(15 suppl). Published online May 25, 2020. 4. Foster NR. Renfro LA. Schi ld SE. et al. Multi trial evaluation of progression-free survival as a surrogate end point for overall survival in first-line extensive stage small·cell lung cancer. J Thorac Oncol. 2015;10{7):1099-1106. 5. Rudin CM, lsmaila N, Hann CL, et al. Treatment of small-cell lung cancer: American Society of Clinical Oncology endorsement of the American College of Chest Physicians Guideline. J Clin Oncol 2015;33(34):4106-4111. 6. Wang S, Zimmermann s. Parikh K. Mansfield AS, Adjei AA. Current diagnosis and management of small·cell lung cancer. Mayo Clin Proc. 2019;94(8):1599· 1622. 7. Seute T. Leffers P, Wilmink JT. ten Velde GPM, Twijnstra A Response of asymptomatic brain metastases from small·cell lung cancer to systemic first-line chemotherapy. J Clin Oncol. 2006;24(13):2079·2083. 8. Parsons HM, Harlan LC, Stevens J L, et al. Treatment of small cell lung cancer in academic and community settings: factors associated with receiving standard therapy and survival. Cancer J. 2014;20(2):97-104.
IMPORTANT SAFETY INFORMATION
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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, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).

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 diarrhoea. Withhold IMFINZI for Grade 2 colitis or diarrhoea; permanently discontinue for Grade 3 or 4 colitis or diarrhoea.

In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, colitis or diarrhoea occurred in 18% of patients, including Grade 3 (1.0%) and Grade 4 (0.1%) immune-mediated colitis. Diarrhoea 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 disorders—Monitor 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 insufficiency—Administer 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 mellitus—Initiate 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.
  • Hypophysitis—Administer 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 extensive-stage SCLC in the CASPIAN study (n=265), the most common adverse reactions (≥20%) were nausea, fatigue/asthenia, and alopecia. The most common Grade 3 or 4 adverse reaction (≥3%) was fatigue/asthenia (3.4%)
  • In patients with extensive-stage SCLC in the CASPIAN study (n=265), IMFINZI was discontinued due to adverse reactions in 7% of the patients receiving IMFINZI plus chemotherapy. 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

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


Please see complete Prescribing Information, including Medication Guide
.

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, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).

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 diarrhoea. Withhold IMFINZI for Grade 2 colitis or diarrhoea; permanently discontinue for Grade 3 or 4 colitis or diarrhoea.

In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, colitis or diarrhoea occurred in 18% of patients, including Grade 3 (1.0%) and Grade 4 (0.1%) immune-mediated colitis. Diarrhoea 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 disorders—Monitor 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 insufficiency—Administer 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 mellitus—Initiate 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.
  • Hypophysitis—Administer 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 extensive-stage SCLC in the CASPIAN study (n=265), the most common adverse reactions (≥20%) were nausea, fatigue/asthenia, and alopecia. The most common Grade 3 or 4 adverse reaction (≥3%) was fatigue/asthenia (3.4%)
  • In patients with extensive-stage SCLC in the CASPIAN study (n=265), IMFINZI was discontinued due to adverse reactions in 7% of the patients receiving IMFINZI plus chemotherapy. 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

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


Please see complete Prescribing Information, including Medication Guide
.

Read More