IMFINZI plus chemotherapy tripled patient survival at three years in the CASPIAN Phase III trial in extensive-stage small cell lung cancer
WILMINGTON, Del.--(BUSINESS WIRE)--Updated results from the CASPIAN Phase III trial showed AstraZeneca?s IMFINZI??(durvalumab) in combination with a choice of chemotherapies, etoposide plus either carboplatin or cisplatin, demonstrated a sustained, clinically meaningful overall survival (OS) benefit at three years for adults with extensive-stage small cell lung cancer (ES-SCLC) treated in the 1st-line setting.
These data, which show the longest survival update ever reported for an immunotherapy treatment in this setting, were presented during a mini-oral session on September 18, 2021, at the European Society of Medical Oncology (ESMO) Congress 2021.
The CASPIAN trial met the primary endpoint of OS in?June 2019, reducing the risk of death by 27% (based on a hazard ratio [HR] of 0.73; 95% confidence interval [CI] 0.59-0.91; p=0.0047), which has formed the basis of regulatory approvals in many countries around the world. Updated results were previously presented during the ASCO20 Virtual Scientific Program in?May 2020?with a median follow up of more than two years.
The latest results for IMFINZI?plus chemotherapy showed sustained efficacy after a median follow up of more than three years for censored patients, with a 29% reduction in the risk of death versus chemotherapy alone (based on an HR of 0.71; 95% CI 0.60-0.86; nominal p=0.0003). Updated median OS was 12.9 months versus 10.5 for chemotherapy.
The results included a planned exploratory analysis, where an estimated 17.6% of patients treated with IMFINZI plus chemotherapy were alive at three years, versus 5.8% of patients treated with chemotherapy alone. The survival benefits were consistent across all subgroups, in line with previous analyses.
Luis Paz-Ares, MD, PhD, Chair, Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain and principal investigator in the CASPIAN Phase III trial said: ?Patients with extensive-stage small cell lung cancer historically have had limited treatment options and still face a dire prognosis, which makes these data showing that three times as many patients survive three years following IMFINZI treatment especially meaningful. These results reinforce IMFINZI plus platinum chemotherapy as an important standard of care in this setting.?
Susan Galbraith, Executive Vice President, Oncology R&D, said: ?This remarkable improvement in survival is an unprecedented achievement at three years for patients with extensive-stage small cell lung cancer. We are deeply committed to helping improve survival rates in this disease with research into new treatment options to transform outcomes at various stages, not only with the CASPIAN trial, but also with the ADRIATIC trial in limited-stage disease.?
IMFINZI plus chemotherapy continued to demonstrate a well-tolerated safety profile consistent with the known profiles of these medicines. Results showed 32.5% of patients experienced a serious adverse event (all causality) with IMFINZI plus chemotherapy versus 36.5% with chemotherapy alone.
IMFINZI in combination with etoposide and either carboplatin or cisplatin is approved in the 1st-line setting of ES-SCLC in more than 55 countries, including the US, Japan, China and across the EU.
IMFINZI is also being tested following concurrent chemoradiation therapy (CRT) in patients with limited-stage SCLC in the ADRIATIC Phase III trial as part of a broad development program. In addition, IMFINZI is also approved to treat non-small cell lung cancer (NSCLC) in the curative-intent setting of unresectable, Stage III disease after CRT in the US, Japan, China, across the EU and in many other countries, based on results from the PACIFIC Phase III trial.
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 2.4% (34/1414), 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 18.3% (87/475) in patients receiving IMFINZI and 12.8% (30/234) in patients receiving placebo. Of the patients who received IMFINZI (475), 1.1% were fatal and 2.7% were Grade 3 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 2% (37/1889) of patients receiving IMFINZI, including Grade 4 (<0.1%) and Grade 3 (0.4%) adverse reactions.
Immune-Mediated Hepatitis
IMFINZI can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 2.8% (52/1889) of patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%) and Grade 3 (1.4%) 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 0.5% (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 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 0.5% (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.
- 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 (34%), fatigue/asthenia (32%), and alopecia (31%). 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
- American Cancer Society. Key Statistics for Lung Cancer. Available at?https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html. Accessed September 2021.
- American Cancer Society. What is Lung Cancer?. Available at?https://www.cancer.org/cancer/lung-cancer/about/what-is.html. Accessed September 2021.
- National Cancer Institute. NCI Dictionary ? Small Cell Lung Cancer. Available at?https://www.cancer.gov/publications/dictionaries/cancer-terms/def/small-cell-lung-cancer. Accessed September 2021.
- Kalemkerian GP,?et al. Treatment Options for Relapsed Small-Cell Lung Cancer: What Progress Have We Made??JCO Oncol Pract. 2018;14:369-370.
- Cancer.Net. Lung Cancer - Small Cell. Available at?https://www.cancer.net/cancer-types/33776/view-all. Accessed September 2021.