EFFICACY

Overall Survival

In unresectable Stage III NSCLC following chemoradiotherapy

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

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 survival in unresectable Stage III NSCLC1

NSCLC=non-small cell lung cancer; OS=overall survival; CI=confidence interval; NR=not reached; 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

In unresectable Stage III NSCLC following chemoradiotherapy

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.5

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*

PFTs=pulmonary function tests; FDG=fluorodeoxyglucose; PET=positron emission tomography; CT=computed tomography; MRI=magnetic resonance imaging; CRT=chemoradiotherapy.

*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.2.2021. ©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 ARs 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

Gy=gray; TTDM=time to death or distant metastasis; ARs=adverse reactions; CR=complete response; PR=partial response; SD=stable disease; EGFR=epidermal growth factor receptor; WHO=World Health Organization; RECIST=Response Evaluation Criteria in Solid Tumors; BICR=blinded independent central review; AJCC=American Joint Committee on Cancer.

*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).

Immune-Mediated Adverse Reactions

Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible

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.

severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment or after discontinuation. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue IMFINZI depending on severity. See Dosing and Administration for specific details. In general, if IMFINZI requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Adverse Reactions

Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment or after discontinuation. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue IMFINZI depending on severity. See Dosing and Administration for specific details. In general, if IMFINZI requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

IMFINZI can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients who did not receive recent prior radiation, the incidence of immune-mediated pneumonitis was 2% (28/1414), including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions. In patients who received recent prior radiation, the incidence of pneumonitis (including radiation pneumonitis) in patients with unresectable Stage III NSCLC following definitive chemoradiation within 42 days prior to initiation of IMFINZI in PACIFIC was 16.6% (79/475) in patients receiving IMFINZI and 13.2% (31/234) in patients receiving placebo. Of the 79 patients who received IMFINZI, 1.1% were fatal and 2.5% were Grade 3-4 adverse reactions. The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to IMFINZI were similar in patients who received IMFINZI as a single agent or with ES-SCLC when in combination with chemotherapy.

Immune-Mediated Colitis

IMFINZI can cause immune-mediated colitis that is frequently associated with diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.6% (31/1889) of patients receiving IMFINZI, including Grade 4 (0.1%) and Grade 3 (0.3%) adverse reactions.

Immune-Mediated Hepatitis

IMFINZI can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 1% (19/1889) of patients receiving IMFINZI, including fatal (<0.1%) and Grade 3 (0.6%) adverse reactions.

Immune-Mediated Endocrinopathies

  • Adrenal Insufficiency: IMFINZI can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Immune-mediated adrenal insufficiency occurred in 0.4% (7/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
  • Hypophysitis: IMFINZI can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate symptomatic treatment including hormone replacement as clinically indicated. Grade 3 hypophysitis/hypopituitarism occurred in <0.1% (1/1889) of patients who received IMFINZI.
  • Thyroid Disorders: IMFINZI can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated.
  • Thyroiditis: Immune-mediated thyroiditis occurred in 0.4% (7/1889) of patients receiving IMFINZI.
  • Hyperthyroidism: Immune-mediated hyperthyroidism occurred in 1.4% (27/1889) of patients receiving IMFINZI.
  • Hypothyroidism: Immune-mediated hypothyroidism occurred in 7.3% (137/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
  • Type 1 Diabetes Mellitus, which can present with diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Grade 3 immune-mediated type 1 diabetes mellitus occurred in <0.1% (1/1889) of patients receiving IMFINZI.

Immune-Mediated Nephritis with Renal Dysfunction

IMFINZI can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (5/1889) of patients receiving IMFINZI, including Grade 3 (0.1%) adverse reactions.

Immune-Mediated Dermatology Reactions

IMFINZI can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), have occurred with PD-1/L-1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Immune-mediated rash or dermatitis occurred in 1.6% (30/1889) of patients receiving IMFINZI, including Grade 3 (0.4%) adverse reactions.

Other Immune-Mediated Adverse Reactions

The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in patients who received IMFINZI or were reported with the use of other PD-1/PD-L1 blocking antibodies.

  • Cardiac/vascular: Myocarditis, pericarditis, vasculitis.
  • Nervous system: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy.
  • Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.
  • Gastrointestinal: Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis.
  • Musculoskeletal and connective tissue disorders: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatic.
  • Endocrine: Hypoparathyroidism
  • Other (hematologic/immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection.

Infusion-Related Reactions

IMFINZI can cause severe or life-threatening infusion-related reactions. Monitor for signs and symptoms of infusion-related reactions. Interrupt, slow the rate of, or permanently discontinue IMFINZI based on the severity. See Dosing and Administration for specific details. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses. Infusion-related reactions occurred in 2.2% (42/1889) of patients receiving IMFINZI, including Grade 3 (0.3%) adverse reactions.

Complications of Allogeneic HSCT after IMFINZI

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/L-1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT.

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. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with IMFINZI 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.

Adverse Reactions

  • In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), the most common adverse reactions (≥20%) 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 receiving 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%) 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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