Approval based on TOPAZ-1 Phase III trial results, which showed IMFINZI combination reduced risk of death by 20% vs. chemotherapy alone
AstraZeneca’s IMFINZI® (durvalumab) has been approved in the US for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC) in combination with chemotherapy (gemcitabine plus cisplatin).
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The approval by the Food and Drug Administration (FDA) was based on the results from the TOPAZ-1 Phase III trial. In an interim analysis of TOPAZ-1, IMFINZI plus chemotherapy reduced the risk of death by 20% versus chemotherapy alone (hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.66-0.97; p=0.021). An estimated one in four (25%) patients treated with IMFINZI plus chemotherapy were still alive at two years compared to one in 10 (10%) treated with chemotherapy alone. Results were consistent across all prespecified subgroups, regardless of PD-L1 expression or tumor location.
BTC is a group of rare and aggressive cancers that occur in the bile ducts and gallbladder.1,2 Approximately 23,000 people in the US are diagnosed with BTC each year.1 These patients have a poor prognosis, with approximately 5% to 15% of patients with BTC surviving five years.3
Aiwu Ruth He, MD, PhD, Associate Professor of Medicine, Leader of the GI Cancer Program, Georgetown Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington DC, and a lead investigator in the TOPAZ-1 Phase III trial, said: ” This approval represents a major step forward for patients with advanced biliary tract cancer, who urgently need new, well-tolerated and effective treatment options after more than a decade of limited innovation. The combination of durvalumab and chemotherapy should become a new standard of care in this setting, having demonstrated significantly improved survival for these patients who have historically faced a poor prognosis.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “For the first time, patients in the US with advanced biliary tract cancer have an immunotherapy-based treatment option that meaningfully extends survival and is well-tolerated. This approval for IMFINZI and chemotherapy advances our ambition to challenge treatment expectations and transform care for patients with gastrointestinal cancers with high unmet need.”
Stacie Lindsey, CEO, Cholangiocarcinoma Foundation, said: “Patients have been waiting a long time for a new, first-line treatment option for biliary tract cancer. The Foundation congratulates AstraZeneca for engaging in rare cancer research, which impacts patients and families nationwide. We are especially grateful to the patients who participated in this trial making it possible for the broader rare disease community to benefit from this treatment.”
The TOPAZ-1 Phase III trial results were presented at the 2022 American Society of Clinical Oncology Gastrointestinal Cancers (ASCO GI) Symposium and published in the New England Journal of Medicine Evidence. IMFINZI plus chemotherapy was generally well tolerated and did not increase the discontinuation rate due to adverse events compared to chemotherapy alone.
In July 2022, IMFINZI plus chemotherapy was added to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as a Category 1 preferred regimen as 1st-line therapy for locally advanced or metastatic BTC based on the data from TOPAZ-1.4
The US regulatory submission for TOPAZ-1 was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. As part of Project Orbis, IMFINZI plus chemotherapy is also under regulatory review for the same indication by the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency (ANVISA), Health Canada, Israel’s Ministry of Health Pharmaceutical Administration, Singapore’s Health Sciences Authority, Switzerland’s Swissmedic and the UK’s Medicines and Healthcare products Regulatory Agency.
The approval was granted after securing Priority Review and Orphan Drug Designation for IMFINZI in the US in this setting. Regulatory applications are also currently under review in Europe, Japan and several other countries based on the TOPAZ-1 results.
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 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.
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% ...