EFFICACY

Progression-Free Survival

11.2-month improvement in median progression-free survival (PFS) See study design

Median PFS was 16.8 months with IMFINZI vs 5.6 months with placebo (p<0.0001)*1

Probability of PFS

IMFINZI® (durvalumab) progression-free survival IMFINZI® (durvalumab) progression-free survival

IMFINZI (n=476)

Placebo (n=237)

16.8

months

(95% CI, 13–18.1)

5.6

months

(95% CI, 4.6–7.8)

Time from randomization (months)

Number of patients at risk

IMFINZI47637730126415986442141

Placebo23716310687522815430

12-month PFS: 56% with IMFINZI vs 35% with placebo†2

18-month PFS: 44% with IMFINZI vs 27% with placebo‡2

48% REDUCTION

in risk of progression or death vs placebo
(HR=0.52) (95% CI, 0.42–0.65)

*Measured based on RECIST v1.1 criteria by blinded independent central review (BICR).2

95% CI was 51%–60% with IMFINZI vs 29%–42% with placebo.2

95% CI was 38%–51% with IMFINZI vs 20%–35% with placebo.2

Overall Survival

Statistically significant overall survival (OS) benefit

Median OS had not yet been reached with IMFINZI vs 28.7 months with placebo (p=0.0025)3

IMFINZI® (durvalumab) overall survival IMFINZI® (durvalumab) overall survival
  • At time of first planned OS analysis, median OS had not yet been reached with IMFINZIII3

NR: not reached.

§95% CI was 62%–70% with IMFINZI vs 49%–62% with placebo.3

IIFor OS, the final analysis was planned when approximately 491 deaths had occurred out of 713 randomized patients (69% maturity). The first planned OS analysis was after 285 deaths. The actual analysis was conducted after 299 deaths for 42% maturity (61% of planned events).3

Median time to death or distant metastasis (TTDM) was over 23 months

Median TTDM2,3

IMFINZI median time to death or distant metastasis was
over 23 months IMFINZI median time to death or distant metastasis was
over 23 months
  • TTDM was evaluated at first planned PFS and OS analyses2,3
  • TTDM is defined as the time from the date of randomization until the first date of distant metastasis or death in the absence of distant metastasis2
  • Distant metastasis is defined as any new lesion that is outside of the radiation field using BICR according to RECIST v1.1 or proven by biopsy2

Incidence and location of new lesions

Incidence of new lesions (%) in the intent-to-treat population at first planned PFS and OS analyses2,3

Incidence and location of new lesions Incidence and location of new lesions
  • New lesions were assessed by RECIST v1.1 criteria by blinded independent central review2,3
  • The presence of one or more new lesions is assessed as progression2,3
  • A lesion identified at a follow-up assessment in an anatomical location that was not scanned at baseline is considered a new lesion2,3

Patients may have had more than one new lesion site.2,3

Clinical Guidelines

National Comprehensive Cancer Network® (NCCN®) recommendations*

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend (Category 1) durvalumab (IMFINZI®) as the only consolidation immunotherapy for patients with unresectable Stage III NSCLC whose disease has not progressed following chemoradiation therapy†4

NSCLC Clinical guidelines NSCLC Clinical guidelines
  • NCCN recommends multidisciplinary evaluations be done before treatment4

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

*For detailed recommendations, see the NCCN Guidelines for NSCLC (available at NCCN.org).

For performance status 0–1.

Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Non-Small Cell Lung Cancer. V.3.2019.

© National Comprehensive Cancer Network, Inc. 2019. 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.

The National Comprehensive Cancer Network 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.

 

Study Design

PACIFIC: A pivotal Phase III study powered to demonstrate significant PFS and OS vs placebo

The PACIFIC study was a randomized, double-blind, placebo-controlled, international study of 713 patients with unresectable Stage III (locally advanced) NSCLC1,2

IMFINZI® (durvalumab) PACIFIC Study design IMFINZI® (durvalumab) PACIFIC Study design
  • PACIFIC study enrollment included patients with Stage IIIA and IIIB disease based on American Joint Committee on Cancer (AJCC) 7th Edition Guidelines2
  • Stage IIIC patients (a new categorization in the AJCC 8th Edition Guidelines) were categorized as Stage IIIB5

    Coprimary endpoints§1

  • Progression-free survival (PFS)II
  • Overall survival (OS)

    Select secondary endpoints§1,2

  • 12-month and 18-month PFSII
  • 24-month OS
  • Time to death or distant metastasisII
  • Overall response rateII

Baseline demographics and disease characteristics of patients in the PACIFIC study

  • Baseline demographics were equal and disease characteristics were well balanced across study groups (IMFINZI, n=476; placebo, n=237)1,2

IMFINZI® (durvalumab) PACIFIC Study baseline demographics and disease characteristicsIMFINZI® (durvalumab) PACIFIC Study baseline demographics and disease characteristics

PD-L1: programmed cell death ligand-1; EGFR: epidermal growth factor receptor.

*Patients received cisplatin or carboplatin plus one 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.1,2

Absence of progression following at least 2 cycles of chemotherapy concurrent with radiation and a WHO performance status of 0 or 1.2

Patients determined to be eligible for randomization within 6 weeks (42 days) following the completion of last dose of platinum-based CRT.2

§Measured from day of randomization and initiation of IMFINZI.2

IIMeasured based on RECIST v1.1 criteria by blinded independent central review (BICR).2

Randomization at enrollment was stratified by baseline demographics.2

#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.2,5

**Retrospectively analyzed in patients with available samples taken prior to concurrent CRT.2

††Assessment of archived tumor samples obtained before CRT.2

 

Read the latest publication for the PACIFIC study in The New England Journal of Medicine.

DOI: 10.1056/NEJMoa1809697

 

Important Safety Information

There are no contraindications for IMFINZI® (durvalumab).

IMFINZI can cause serious, potentially fatal adverse reactions including immune-mediated pneumonitis, hepatitis, colitis or diarrhea, endocrinopathies, nephritis, rash or dermatitis, 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 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. In the PACIFIC study, the incidence of pneumonitis (including radiation pneumonitis) was 34%, including Grade 3 (3.4%) and Grade 5 (1.1%) pneumonitis in the IMFINZI arm. In the PACIFIC study, pneumonitis led to discontinuation of IMFINZI in 6% of patients.

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%) 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%). 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. Bullous dermatitis and Stevens Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN) have 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. 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%). 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 reaction (≥3%) was 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 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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