EFFICACY

Overall Survival

IMFINZI® (durvalumab) demonstrated consistent overall survival in 2-year through 4 year analyses1-3

2-year primary OS analysis (25.2 months median follow-up): OS was statistically significant2,3*

  • Median OS: Not reached with IMFINZI (95% CI, 34.7-NR) vs 28.7 months with placebo (95% CI, 22.9-NR)
  • 32% reduction in risk of death vs placebo (HR=0.68; 95% CI, 0.53-0.87; P=0.0025)
  • 2-year OS rate was 66% with IMFINZI vs 55% with placebo

Updated post-hoc OS analysis at ~4 years after randomization1†

  • Median OS: 47.5 months with IMFINZI (95% CI, 38.4-52.6) vs 29.1 months with placebo (95% CI, 22.1-35.1)
  • 29% reduction in risk of death vs placebo (HR=0.71; 95% CI, 0.57-0.88)
  • 4-year OS rate was 50% with IMFINZI vs 36% with placebo

In unresectable Stage III NSCLC following chemoradiotherapy,

With IMFINZI® (durvalumab), 50% of patients were alive at 4 years1†

4-YEAR OVERALL SURVIVAL UPDATE1†

See 4-year overall survival for IMFINZI in unresectable Stage III NSCLC following CRT See 4-year overall survival for IMFINZI in unresectable Stage III NSCLC following CRT

IMFINZI® (durvalumab): Unprecedented 4 years median overall survival1

OS=overall survival; NR=not reached; CI=confidence interval; HR=hazard ratio.

*The primary 2-year OS analysis was conducted after 299 deaths for 42% maturity (61% of targeted events).2,3

The post-hoc 4-year OS analysis was conducted at ~4 years after last patient was randomized and was not powered to show statistical significance. OS rates with IMFINZI vs placebo were: 83% (95% CI, 79.4-86.2) vs 75% (95% CI, 68.5-79.7) at 12 months, 66% (95% CI, 61.8-70.4) vs 55% (95% CI, 48.6-61.4) at 24 months, 57% (95% CI, 52.3-61.4) vs 44% (95% CI, 37.0-49.9) at 36 months, and 50% vs 36% at 48 months.1,4

 

Progression-Free Survival

IMFINZI® (durvalumab) demonstrated consistent results in median PFS in 1-year through 4-year analyses1,2,5

1-year primary PFS analysis (14.5 months median follow-up): PFS was statistically significant2,5*

  • Median PFS: 16.8 months with IMFINZI (95% CI, 13.0-18.1) vs 5.6 months with placebo (95% CI, 4.6-7.8)
  • 48% reduction in the risk of progression or death vs placebo (HR=0.52; 95% CI, 0.42-0.65; P<0.0001)
  • 1-year PFS rate was 56% with IMFINZI vs 35% with placebo*

Updated post-hoc PFS analysis at ~4 years after randomization1†

  • Median PFS: 17.2 months with IMFINZI (95% CI, 12.3-23.8) vs 5.6 months with placebo (95% CI, 4.6-7.7)
  • 45% reduction in risk of progression or death vs placebo (HR=0.55; 95% CI, 0.44-0.67)
  • 4-year PFS rate was 35% with IMFINZI vs 20% with placebo

With IMFINZI® (durvalumab), 35% of patients remained progression free at 4 years1

4-YEAR PROGRESSION-FREE SURVIVAL UPDATE1†

IMFINZI progression-free survival rates IMFINZI progression-free survival rates

PFS=progression-free survival; RECIST=Response Evaluation Criteria in Solid Tumors; BICR=blinded independent central review.

*95% CI was 51% to 60% with IMFINZI vs 29% to 42% with placebo.1

Measured based on RECIST v1.1 criteria by BICR. The primary PFS analysis was conducted after 371 events (81% of targeted 458 events) with a median follow-up of 14.5 months. The post-hoc 4-year PFS analysis was conducted at ~4 years after last patient was randomized and was not powered to show statistical significance.1,5

 

Clinical Guidelines

National Comprehensive Cancer Network® (NCCN®) Category 1 recommendation for durvalumab (IMFINZI®) in unresectable Stage III NSCLC following chemoradiotherapy6*

National Comprehensive Cancer Network® (NCCN®) Category 1 recommendation for durvalumab (IMFINZI®) in unresectable Stage III NSCLC following CRTNational Comprehensive Cancer Network® (NCCN®) Category 1 recommendation for durvalumab (IMFINZI®) in unresectable Stage III NSCLC following CRT

NCCN

CATEGORY 1

Durvalumab (IMFINZI®) is the only Category 1 post-CRT consolidation immunotherapy for unresectable Stage III NSCLC6*

*Durvalumab (IMFINZI®) is recommended (Category 1) as consolidation immunotherapy for performance status 0 to 1 and no disease progression after 2 or more cycles of definitive concurrent CRT. The National Comprehensive Cancer Network® (NCCN®) makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. For detailed recommendations, see the NCCN Guidelines® for NSCLC at NCCN.org. Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Non-Small Cell Lung Cancer. V.8.2020. ©National Comprehensive Cancer Network, Inc. 2020. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of NCCN. To view the most recent and complete version of the NCCN Guidelines®, go online to NCCN.org. The NCCN Guidelines® are a work in progress that may be refined as often as new significant data becomes available.6

Some Stage III NSCLC is resectable.6

See the NCCN Guidelines® for detailed recommendations about concurrent chemoradiation regimens.

 

Consider IMFINZI® (durvalumab)

The only approved immunotherapy in unresectable Stage IIIA, IIIB, and IIIC NSCLC following chemoradiotherapy2,5*

The only approved immunotherapy in unresectable Stage IIIA, IIIB, and IIIC NSCLC following CRT The only approved immunotherapy in unresectable Stage IIIA, IIIB, and IIIC NSCLC following CRT

PD-1=programmed cell death protein 1; PD-L1=programmed death-ligand 1.

*In patients with unresectable Stage III NSCLC whose disease has not progressed following concurrent platinum-based chemoradiotherapy.2

PACIFIC study enrollment was based on the Staging Manual in Thoracic Oncology, version 7, of the International Association for the Study of Lung Cancer. The 8th edition includes the addition of Stage IIIC; in the PACIFIC study, these patients were categorized as Stage IIIB.5,10

Only PD-1 and PD-L1 inhibitors with approved NSCLC indications are included.2,7-9

§For performance status 0 to 1, and no disease progression after 2 or more cycles of definitive concurrent CRT.6

The National Comprehensive Cancer Network® (NCCN®) makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. For detailed recommendations, see the NCCN Guidelines® for NSCLC at NCCN.org.

 

Study Design

PACIFIC: Large, double-blind Phase III study powered to demonstrate significant overall survival and PFS vs placebo2

  • 713 patients with unresectable Stage III NSCLC were enrolled2,5
PACIFIC: Large, Phase III study of IMFINZI powered to demonstrate overall survival and PFS vs placebo PACIFIC: Large, Phase III study of IMFINZI powered to demonstrate overall survival and PFS vs placebo
  • Randomized, double-blind, placebo-controlled, international study2,5

Coprimary endpoints2,5‡

  • PFS§
  • OS

Select secondary endpoints2,5‡

  • 12-month PFS§
  • 18-month PFS§
  • 24-month OS
  • TTDM§
  • Overall response rate§
  • Duration of response§
  • Health-related quality of life (HRQoL)
  • The majority of patients received carboplatin + paclitaxel or cisplatin + etoposide as part of their CRT regimen2,5
    • Consolidation chemotherapy after radiation was not permitted5
    • 27% of patients received optional induction chemotherapy5
  • Patients with residual ≤Grade 2 CRT AEs or ≤Grade 1 CRT-induced pneumonitis were included in the study5∥

IMFINZI was evaluated in patients who had not progressed following CRT2,5,10

Unresectable Stage IIIA, IIIB, IIIC NSCLC

Patients with CR, PR, or SD

Squamous or Nonsquamous histology

Regardless of PD-L1 status (no testing required)

Patients were randomized to receive IMFINZI® (durvalumab) within 42 days of CRT completion2

Patients were enrolled regardless of PD-L1 expression, EGFR/ALK status, or histology2,5

Baseline Characteristics#

IMFINZI (n=476)

Placebo (n=237)

Gender

  • Male
  • 70%
  • 70%
  • Female
  • 30%
  • 30%

Age

  • <65 years
  • 55%
  • 55%
  • ≥65 years
  • 45%
  • 45%

Smoking history

  • Current/former smokers
  • 91%
  • 91%
  • Never
    smokers
  • 9%
  • 9%

Disease Characteristics

IMFINZI (n=476)

Placebo (n=237)

Stage at diagnosis

  • IIIA
  • 53%
  • 53%
  • IIIB
  • 45%
  • 45%

Histology

  • Squamous
  • 47%
  • 43%
  • Nonsquamous
  • 53%
  • 57%

PD-L1 expression**

  • ≥25%
  • 24%
  • 91%
  • <25%
  • 39%
  • 44%
  • Unknown
  • 37%
  • 37%

EGFR mutation††

  • Positive
  • 6%
  • 6%
  • Negative
  • 66%
  • 70%
  • Unknown
  • 28%
  • 24%
  • The PACIFIC study enrollment included patients with Stage IIIA and IIIB disease based on the Staging Manual in Thoracic Oncology, version 7, of the International Association for the Study of Lung Cancer5
    • Stage IIIC patients (a new categorization in the 8th edition guidelines) were categorized as Stage IIIB10

Baseline characteristics were well balanced across study groups5

AEs=adverse events; EGFR=epidermal growth factor receptor; ALK=anaplastic lymphoma kinase; TTDM=time to death or distant metastasis.

*Patients received cisplatin or carboplatin plus 1 of the following: etoposide, vinorelbine, paclitaxel, docetaxel, vinblastine, or pemetrexed with radiation. All patients received definitive radiotherapy as per protocol, of which 92% received a total radiation dose of 54 Gy to 66 Gy.2,5

Absence of progression following at least 2 cycles of chemotherapy concurrent with radiation and WHO performance status of 0 or 1.5

Measured from day of randomization and initiation of IMFINZI.5

§Measured based on RECIST v1.1 criteria by BICR.5

||Initially, patients with Grade 1 CRT-induced pneumonitis were excluded from the study.5

According to the AJCC Cancer Staging Manual, 8th edition of the TNM classification for lung cancer derived from databases for the International Association for the Study of Lung Cancer; the study included patients who are now classified as Stage IIIC.3,5,11,12

#Randomization at enrollment was stratified by baseline demographics.5

**Retrospectively analyzed in patients with available samples taken prior to concurrent CRT.5

††Assessment of archived tumor samples obtained before CRT.5

 

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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