IMFINZI Demonstrated Unprecedented Survival in Unresectable Stage III Lung Cancer With 43% Of Patients Surviving Five Years
WILMINGTON, Del.--(BUSINESS WIRE)--Updated results from the positive PACIFIC Phase III trial showed AstraZeneca?s IMFINZI??(durvalumab) demonstrated a sustained, clinically meaningful overall survival (OS) and progression-free survival (PFS) benefit at five years in patients with unresectable Stage III non-small cell lung cancer (NSCLC) who had not progressed following concurrent chemoradiation therapy (CRT).
Lung cancer is the leading cause of cancer death in the US, accounting for about a quarter of all cancer deaths, and 80-85% of patients with lung cancer have NSCLC.1?One in four patients with NSCLC are diagnosed at Stage III, where the majority of tumors are unresectable (cannot be removed with surgery).2-3?The approval of IMFINZI?in this setting, based on the results of this trial, was the first new treatment to be available to these patients in decades.4-6
Results from the updated post-hoc analyses showed an estimated five-year OS rate of 42.9% for patients treated with IMFINZI?versus 33.4% for those on placebo after CRT. Median OS was 47.5 months for IMFINZI?versus 29.1 for placebo. Following a maximum treatment course of one year, an estimated 33.1% of patients treated with IMFINZI?had not progressed five years after enrollment versus 19% for placebo. These results build on the primary PFS and OS analyses published in?The New England Journal of Medicine?in?2017?and?2018, which demonstrated a sustained, significant benefit with IMFINZI?for these primary endpoints.7,8
David Spigel, MD, Chief Scientific Officer at the Sarah Cannon Research Institute, and investigator in the PACIFIC trial, said: ?This trial has once again set a new precedent in the treatment of patients with unresectable Stage III non-small cell lung cancer. Historically, only 15-30% of these patients survived five years but these results show that with up to one year of treatment with IMFINZI, an estimated 43% of patients are still alive at five years. Moreover, three quarters of these patients had also not progressed in that time. This is a momentous achievement at the five-year landmark in this curative-intent setting.?
Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: ?Five-year survival is a clinically significant and emotionally meaningful milestone for people with cancer and their families, and it's incredible to see the majority of patients surviving that long have not progressed four years after completing treatment. These results ? the first of their kind in Stage III unresectable lung cancer ? reinforce the long-term benefit of IMFINZI?as the established standard of care in this curative-intent setting. With trials like PACIFIC and our comprehensive development program in early-stage disease across cancer settings, our strategy is to improve cancer outcomes by treating patients as early as possible, aiming to deliver life-changing treatments that increase the potential for cure.?
In the primary OS analysis of the PACIFIC Phase III trial, the most common adverse events (AEs) (greater than or equal to 20%) among patients treated with IMFINZI?versus placebo were cough (35.2% versus 25.2%), fatigue (24.0% versus 20.5%), dyspnea (22.3% versus 23.9%) and radiation pneumonitis (20.2% versus 15.8%). A grade 3 or 4 AE was experienced by 30.5% of patients treated with IMFINZI?versus 26.1% for placebo, and 15.4% of patients discontinued treatment due to AEs with IMFINZI?versus 9.8% for placebo.8
These results were presented on June 4 during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.
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 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 2.0% (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 1.0% (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.
- Cardiac/vascular: Myocarditis, pericarditis, vasculitis.
- Nervous system: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barr? 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.
- 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
- In patients with extensive-stage SCLC in the CASPIAN study receiving IMFINZI plus chemotherapy (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 receiving IMFINZI plus chemotherapy (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
US-52747 Last Updated 6/21