FDA Grants Breakthrough Therapy Designation, Priority Review to AstraZeneca’s Imfinzi for the Treatment of Limited-Stage Small Cell Lung Cancer

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The FDA has granted Breakthrough Therapy Designation and Priority Review to AstraZeneca’s Infimzi (durvalumab), indicated for the treatment of limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following platinum-based concurrent chemoradiotherapy (cCRT). According to the company, both the Breakthrough Therapy designation and Priority Review were based on results from the Phase III ADRIATIC trial, which demonstrated a significant improvement in overall survival (OS) and progression-free survival (PFS) compared to placebo in patients with LS-SCLC.¹

“This Priority Review reinforces the potential of Imfinzi to transform outcomes for patients as the first and only immunotherapy to demonstrate a survival benefit in limited-stage small cell lung cancer. There is an urgent need for new treatment options that improve upon the standard of care in this setting, which has not changed in forty years, and we look forward to working with the FDA to bring IMFINZI to patients as quickly as possible,” said Susan Galbraith, EVP, oncology, R&D, AstraZeneca, in a press release.

The ADRIATIC trial is a randomized, double-blind, placebo-controlled, multi-center global trial that evaluated Imfinzi monotherapy and Imfinzi plus Imjudo (tremelimumab-actl) versus placebo in 730 patients with LS-SCLC who had not progressed following cCRT. Patients were randomized to receive a 1500 mg fixed dose of Imfinzi as a monotherapy or with Imjudo 75 mg every four weeks for up to four doses/cycles each, followed by Imfinzi every four weeks for up to 24 months. The primary endpoints of the study were PFS and OS for monotherapy versus placebo, while secondary endpoints OS and PFS for Imfinzi plus Imjudo versus placebo, safety and quality of life measures.

Results found that Imfinzi reduced the risk of death by 27% versus placebo. Additionally, the median OS was 55.9 months for Imfinzi compared to 33 months for placebo. Further, an estimated 57% of patients treated with Imfinzi were alive three years after starting treatment as opposed to 48% in the placebo group, Imfinzi reduced the risk of disease progression or death by 24%, median PFS was 16.6 months, and 46% of patients treated with Imfinzi had not experienced disease progression at two years.

AstraZeneca stated that the safety profile of Imfinzi was manageable and consistent with the known profile of this medicine, while no new safety signals were identified. AstraZeneca warned that immune-mediated adverse events (AEs) can occur in at any time after starting treatment or after discontinuation in any organ system or tissue. AEs included pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, dermatology reactions, pancreatitis, infusion-related reactions, complications of allogeneic HSCT, and embryo-fetal toxicity. Common AEs included upper respiratory tract infections, dyspnea, rash, pneumonia, nausea, fatigue, musculoskeletal pain, and decreased appetite.¹

According to Yale Medicine, SCLC accounts for approximately 15% of all lung cancers in the United States on a yearly basis. It is more aggressive than non-small cell lung cancer, and rapidly spreads throughout the body.²

“Due to how quickly it grows and spreads, in 60% of SCLC cases the cancer has already metastasized to other areas in the body by the time it is diagnosed. Common sites for metastasis are the lymph nodes, liver, bones, adrenal glands and brain. When SCLC metastasizes, the cancer can cause symptoms that are not typically associated with lung cancer, including bone pain, seizures, confusion and paralysis,” reports Yale Medicine.

References

1. IMFINZI® (durvalumab) granted Priority Review and Breakthrough Therapy Designation for patients with limited-stage small cell lung cancer in the US. Business Wire. August 15, 2024. Accessed August 15, 2024. https://www.businesswire.com/news/home/20240815340200/en/IMFINZI%C2%AE-durvalumab-granted-Priority-Review-and-Breakthrough-Therapy-Designation-for-patients-with-limited-stage-small-cell-lung-cancer-in-the-US

2. Small Cell Lung Cancer. Yale Medicine. Accessed August 15, 2024. https://www.yalemedicine.org/conditions/small-cell-lung-cancer#:~:text=There%20are%20two%20primary%20forms,the%20United%20States%20each%20year.