IMFINZI-based treatment before and after surgery reduced the risk of disease recurrence, progression events or death by 32% in resectable non-small cell lung cancer in the AEGEAN Phase III trial
AstraZeneca's IMFINZI® (durvalumab) has demonstrated promising results in the AEGEAN Phase III trial for resectable early-stage non-small cell lung cancer (NSCLC). The trial reported that patients receiving IMFINZI plus neoadjuvant chemotherapy achieved a pathologic complete response (pCR) rate of 17.2%, significantly higher than the 4.3% for chemotherapy alone—a difference of 13% (p=0.000036). Additionally, event-free survival (EFS) showed a 32% risk reduction in recurrence compared to chemotherapy alone. The trial, involving 802 patients across 264 centers globally, aims to provide a new treatment option for lung cancer patients. There were no new safety signals observed. AstraZeneca plans to discuss these data with regulatory authorities in pursuit of approval.
- IMFINZI plus neoadjuvant chemotherapy resulted in a pCR rate of 17.2% vs. 4.3% for chemotherapy alone.
- Statistically significant EFS improvement with a 32% reduction in risk compared to chemotherapy alone.
- Successful treatment completion rate for IMFINZI was 77.6%, comparable to 76.7% for chemotherapy alone.
- None.
Results presented at AACR 2023 found that four times as many patients treated with Imfinzi plus chemotherapy before surgery achieved pathologic complete response versus those treated with neoadjuvant chemotherapy alone
The combination of IMFINZI and neoadjuvant chemotherapy also demonstrated a statistically significant and meaningful improvement in pathologic complete response (pCR), a dual primary endpoint, compared to neoadjuvant chemotherapy alone, at a previously reported interim analysis. The final analysis was consistent with these previously announced positive results.
Results will be presented today in a plenary session at the
In a planned interim analysis of EFS, patients treated with the IMFINZI-based regimen before and after surgery showed a
Summary of results: AEGEAN
|
IMFINZI-based regimen
|
Chemotherapy alone
|
pCR |
||
Number of patients |
63 (17.2) |
16 (4.3) |
Difference in pCR rate % ( |
13.0 (8.7–17.6)a |
|
p-value |
p=0.000036
|
|
EFS |
||
Number of patients with event (%) |
98 (26.8) |
138 (36.9) |
Median EFS ( |
NR (31.9-NR) c |
25.9 (18.9-NR) |
Hazard ratio ( |
0.68 (0.53-0.88)d |
|
p-value |
0.003902e |
|
Data maturity |
|
|
aCIs by stratified Miettinen and Nurminen’s method.
|
IMFINZI was generally well tolerated and no new safety signals were observed in the neoadjuvant and adjuvant settings. Further, adding IMFINZI to neoadjuvant chemotherapy was consistent with the known profile for this combination and did not compromise patients' ability to complete surgery versus chemotherapy alone. Of patients treated with the IMFINZI-based regimen,
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 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 USPI 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
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
Immune-Mediated Hepatitis
IMFINZI can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in
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
0.5% (9/1889) 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 patientswho 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
0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1% ) adverse reactions. -
Hyperthyroidism: Immune-mediated hyperthyroidism occurred in
2.1% (39/1889) of patients receiving IMFINZI. -
Hypothyroidism: Immune-mediated hypothyroidism occurred in
8.3% (156/1889) 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
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
Other Immune-Mediated Adverse Reactions
The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than
- 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 USPI 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
Complications of Allogeneic HSCT after IMFINZI
Fatal and other serious complications can occur in patients
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. In females of reproductive potential, verify pregnancy status prior to initiating IMFINZI and advise them to use effective contraception during treatment with IMFINZI and for 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 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 in29% 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 refer to the full Prescribing Information and Medication Guide for important dosage modification and management information specific to adverse reactions.
Notes
Lung cancer
Each year, an estimated 2.2 million people are diagnosed with lung cancer globally.1 Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.1 Lung cancer is broadly split into NSCLC and small cell lung cancer (SCLC), with 80
The majority of NSCLC patients are diagnosed with advanced disease while approximately 25
The majority of patients with resectable disease eventually develop recurrence despite complete tumor resection and adjuvant chemotherapy.4 Only around 56
AEGEAN
AEGEAN is a randomized, double-blind, multi-center, placebo-controlled global Phase III trial evaluating IMFINZI as perioperative treatment for patients with resectable Stage IIA-IIIB (Eighth Edition AJCC Cancer Staging Manual) NSCLC, irrespective of PD-L1 expression. Perioperative therapy includes treatment before and after surgery, also known as neoadjuvant/adjuvant therapy. In the trial, 802 patients were randomised to receive a 1500mg fixed dose of IMFINZI plus chemotherapy or placebo plus chemotherapy every three weeks for four cycles prior to surgery, followed by IMFINZI or placebo every four weeks (for up to 12 cycles) after surgery. Patients with known EGFR or ALK genomic tumor aberrations were excluded from the primary efficacy analyses.
In the AEGEAN trial, the primary endpoints were pCR, defined as no viable tumor in the resection specimen (including lymph nodes) following neoadjuvant therapy, and EFS, defined as the time from randomization to an event like tumor recurrence, progression precluding definitive surgery, or death. Key secondary endpoints were major pathologic response, defined as residual viable tumor of less than or equal to
IMFINZI®
IMFINZI® (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumor's immune-evading tactics and releasing the inhibition of immune responses.
IMFINZI is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after chemoradiation therapy based on the PACIFIC Phase III trial.
IMFINZI is also approved in the US, EU,
In addition to its indications in lung cancer, IMFINZI is also approved in combination with chemotherapy in locally advanced or metastatic biliary tract cancer in the US, EU,
Since the first approval in
As part of a broad development program, IMFINZI is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, several gastrointestinal (GI) cancers, ovarian cancer, endometrial cancer and other solid tumors.
The Company's comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including tremelimumab-actl and gefitinib; IMFINZI and tremelimumab-actl; fam-trastuzumab deruxtecan-nxki and datopotamab deruxtecan in collaboration with Daiichi Sankyo; savolitinib in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.
The Company's focus is on some of the most challenging cancers. It is through persistent innovation that
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References
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World Health Organization . International agency for research on cancer. lung fact sheet. AccessedMarch 2023 . Available at: https://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf. -
LUNGevity Foundation . Types of lung cancer. AccessedMarch 2023 . Available at: https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer. - Cheema PK, et al. Perspectives on treatment advances for stage III locally advanced unresectable non-small-cell lung cancer. Curr Oncol. 2019;26(1):37-42.
- Cagle PT, et al. Lung cancer biomarkers: present status and future developments. Arch Pathol Lab Med. 2013;137(9):1191-1198.
- Le Chevalier T. Adjuvant chemotherapy for resectable non-small-cell lung cancer: where is it going? Ann Oncol. 2010;21 Suppl 7:vii196-198.
- Goldstraw P, et al. The IASLC lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer. J Thorac Oncol. 2016;11(1):39-51.
- Sethi S, et al. Incidental nodule management – should there be a formal process? J Thorac Dis. 2016;8(Suppl 6):S494-S497.
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LUNGevity Foundation . Screening and early detection. AccessedMarch 2023 . Available at: https://lungevity.org/for-patients-caregivers/lung-cancer-101/screening-early-detection. - Pignon JP, et al. Lung adjuvant cisplatin evaluation: A pooled analysis by the LACE collaborative group. J Clin Oncol. 2008;26(21):3552-3559.
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