WILMINGTON, Del.–(BUSINESS WIRE)–AstraZeneca’s TAGRISSO® (osimertinib) has received acceptance for its supplemental New Drug Application (sNDA) and has also been granted Priority Review in the US for the adjuvant treatment of patients with early-stage (IB, II and IIIA) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after complete tumor resection with curative intent.
While up to 30% of all patients with NSCLC may be diagnosed early enough to have potentially curative surgery, disease recurrence is still common in early-stage disease and nearly half of patients diagnosed in Stage IB, and over three quarters of patients diagnosed in Stage IIIA, experience recurrence within five years.1-4
The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions, or enhancing patient compliance. The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is during the first quarter of 2021.
Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: “Patients with early-stage EGFR-mutated lung cancer are still at considerable risk of recurrence after surgery and adjuvant chemotherapy, and new targeted treatment options are critical to improving outcomes for these patients. This expedited review underscores the unprecedented disease-free survival benefit TAGRISSO brings to patients in the adjuvant setting, and we will continue working with the FDA to provide this practice-changing treatment to patients as quickly as possible.”
The sNDA was based on results from the ADAURA Phase III trial showing TAGRISSO demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) in the primary analysis population of patients with Stage II and IIIA EGFRm NSCLC, and also in the overall trial population of patients with Stage IB-IIIA disease, a key secondary endpoint.
In April 2020, an Independent Data Monitoring Committee recommended for the trial to be unblinded two years early, based on its determination of overwhelming efficacy. Investigators and patients continue to participate in the trial and remain blinded to treatment. The results from the ADAURA trial were presented during the plenary session of the American Society of Clinical Oncology ASCO20 Virtual Scientific Program in May 2020 and were recently published in The New England Journal of Medicine.
TAGRISSO received Breakthrough Therapy Designation in this setting in July 2020. TAGRISSO is approved for both the 1st-line treatment of patients with metastatic EGFRm NSCLC and for the treatment of metastatic EGFR T790M mutation-positive NSCLC in the US, Japan, China, the EU and many other countries around the world.
SELECT SAFETY INFORMATION
- Interstitial lung disease (ILD)/pneumonitis occurred in patients treated with TAGRISSO, some of which were fatal. Withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening respiratory symptoms. Permanently discontinue if confirmed
- Monitor patients who have a history or predisposition for QTc prolongation or those who are taking medications that are known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia
- Cardiomyopathy occurred in TAGRISSO-treated patients, some of which were fatal. Monitor patients with cardiac risk factors and assess left ventricular ejection fraction in patients who develop symptoms during treatment. Permanently discontinue TAGRISSO in patients with symptomatic congestive heart failure
- Promptly refer patients with signs and symptoms of keratitis to an ophthalmologist
- Withhold TAGRISSO if Stevens-Johnson syndrome or erythema multiforme major is suspected and permanently discontinue if confirmed
- Verify pregnancy status of women prior to use. Advise women to use effective contraception during treatment with TAGRISSO and for 6 weeks after the final dose. Advise men to use effective contraception during treatment with TAGRISSO and for 4 months after the final dose
- Most common adverse reactions (≥20%) were diarrhea, rash, dry skin, nail toxicity, stomatitis, fatigue, and decreased appetite
- TAGRISSO is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
- TAGRISSO is indicated for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy
For additional information, please see the full Prescribing Information, including Patient Information.
About Lung cancer
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.5 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.6 The majority of all NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.1-3
For those with resectable tumors, the majority of patients eventually develop recurrence despite complete tumor resection and adjuvant chemotherapy.4 Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition.7-8
Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.9-11 These patients are particularly sensitive to treatment with EGFR-tyrosine kinase inhibitors (TKIs) which block the cell-signalling pathways that drive the growth of tumor cells.12
ADAURA is a randomized, double-blinded, global, placebo-controlled Phase III trial in the adjuvant treatment of 682 patients with Stage IB, II, IIIA EGFRm NSCLC following complete tumor resection and adjuvant chemotherapy as indicated. Patients were treated with TAGRISSO 80mg once-daily oral tablets or placebo for three years or until disease recurrence.
The trial enrolled in more than 200 centers across more than 20 countries, including the US, in Europe, South America, Asia and the Middle East. The primary endpoint is DFS in Stage II and IIIA patients and a key secondary endpoint is DFS in Stage IB, II and IIIA patients. The data readout was originally anticipated in 2022. The trial will continue to assess overall survival.
TAGRISSO® (osimertinib) is a third-generation, irreversible EGFR-TKI with clinical activity against central nervous system metastases. TAGRISSO 40mg and 80mg once-daily oral tablets have received approval in the US, Japan, China, the EU and many countries around the world for 1st-line EGFRm metastatic NSCLC and EGFR T790M mutation-positive metastatic NSCLC.
AstraZeneca in lung cancer
AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage development for the treatment of different forms of lung cancer spanning different histologies, several stages of disease, lines of therapy and modes of action.
AstraZeneca aims to address the unmet needs of patients with EGFRm tumors as a genetic driver of disease with the approved medicines gefitinib and TAGRISSO and its ongoing LAURA, NeoADAURA and FLAURA2 Phase III trials.
AstraZeneca is committed to addressing tumor mechanisms of resistance through the ongoing Phase II trials SAVANNAH and ORCHARD, which test TAGRISSO in combination with savolitinib, a selective inhibitor of c-MET receptor tyrosine kinase, along with other potential new medicines.
AstraZeneca in oncology
AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.
By harnessing the power of six scientific platforms – Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics and Cell Therapies – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas – Oncology, Cardiovascular, Renal & Metabolism and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit https://www.astrazeneca-us.com/ and follow us on Twitter @AstraZenecaUS.
1. Cagle P, et al. Lung Cancer Biomarkers: Present Status and Future Developments. Arch Path Lab Med. 2013;137:1191-1198.
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4. Pignon et al. Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group. J Clin Oncol 2008;26:3552-3559.
5. World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf. Accessed August 2020.
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11. Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a Review of Available Methods and Their Use for Analysis of Tumour Tissue and Cytology Samples. J Clin Pathol. 2013:66;79-89.
12. Cross DA, et al. AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer. Cancer Discov. 2014;4(9):1046-1061.