AstraZeneca's Tagrisso Shows Overwhelming Efficacy in Phase III ADAURA Trial for Early-Stage EGFR-Mutated NSCLC, Leading to Early Unblinding

April 11, 2020 News /BioValleyBIOON/ --AstraZeneca(AstraZeneca) recently announced that the Phase III ADAURA study, evaluating the targeted anticancer drug Tagrisso (Chinese brand name: Taisisha; generic name: osimertinib) as adjuvant therapy for early-stage (Stage IB/II/IIIA) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC), will be unblinded ahead of schedule due to its overwhelming efficacy. Tagrisso is an oral, small-molecule, third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). It is estimated that slightly more than 60% of NSCLC patients are diagnosed with early-stage (Stage I–III) disease.

It is worth mentioning that,ADAURA is the first global study to demonstrate statistically significant and clinically meaningful benefits of an EGFR inhibitor in the adjuvant treatment of lung cancer.Clinical Trials。Based on the study results, AstraZeneca has already advanced its regulatory submission plan for Tagrisso as adjuvant therapy for EGFRm NSCLC.

The ADAURA study is a randomized, double-blind, global, placebo-controlled Phase III trial conducted in 682 patients with early-stage (Stage IB/II/IIIA) EGFR-mutant non-small cell lung cancer (EGFRm-NSCLC) who had receivedTumorComplete resection and optional standard postoperative adjuvant chemotherapy were used to evaluate the efficacy and safety of Tagrisso in the adjuvant setting. In the study, patients in the experimental arm received Tagrisso 80 mg orally once daily for three years or until disease recurrence. The trial was conducted at more than 200 clinical centers across over 20 countries in Europe, South America, Asia, and the Middle East. The primary endpoint was disease-free survival (DFS), with initial data readout expected in 2022.

The Independent Data Monitoring Committee (IDMC) determined, following its assessment, that the study had achieved overwhelmingly positive efficacy results. Based on the IDMC’s recommendation, AstraZeneca made the decision to unblind the study early. The study will continue to evaluate the secondary endpoint of overall survival (OS). During communications with AstraZeneca, the IDMC did not raise any new safety concerns. The study data will be presented at an upcoming medicalConferencepublished above.

AstraZenecaTumorJosé Baselga, Executive Vice President of Research and Development, stated: “We are very excited about the recommendation to unblind the Phase III ADAURA trial early and by these unprecedented results achieved in patients with early-stage EGFRm NSCLC. Lung cancer is a devastating disease, and for the first time, EGFR-targeted therapies can offer the hope of a cure.”

Last September, AstraZeneca in 2019 EuropeTumorThe European Society for Medical Oncology (ESMO) Annual Congress announced the overall survival (OS) results from the Phase III FLAURA study of Tagrisso in lung cancer. Based on these results,Tagrisso is the only drug with a median overall survival (OS) exceeding 3 years in the first-line treatment of EGFR-mutated, locally advanced or metastatic non-small cell lung cancer (NSCLC).Furthermore, Tagrisso also prolonged progression-free survival in patients with central nervous system metastases.

The specific data are as follows: Compared with the gefitinib or erlotinib (previous standard EGFR-TKI drugs) treatment groups, the Tagrisso treatment group demonstrated statistically and clinically significant improvements in the key secondary endpoint of overall survival (OS) (HR=0.799, 95% CI: 0.641–0.997, p=0.0462). The median OS was 38.6 months in the Tagrisso group versus 31.8 months in the control group. After three years of treatment, 28% of patients in the Tagrisso group and 9% of patients in the control group were still receiving first-line study medication. Furthermore, Tagrisso reduced the risk of central nervous system (CNS) disease progression by 52% and prolonged the time to CNS disease progression or death in patients with CNS metastases (HR=0.48, 95% CI: 0.26–0.86, p=0.014). In this study, the safety and tolerability profiles of Tagrisso and standard EGFR-TKIs were consistent with the known properties of each drug.

Lung cancer is the leading cause of cancer-related deaths in both men and women, accounting for approximately one-fifth of all cancer deaths, surpassingBreast Cancer, the sum of prostate cancer and colorectal cancer. Lung cancer is broadly classified into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), with NSCLC accounting for 80–85%.

Approximately 10–15% of NSCLC patients in the United States and Europe, and approximately 30–40% in Asia, have EGFR-mutated (EGFRm) NSCLC. These patients are particularly sensitive to treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), which block the driverTumorCell signaling pathways involved in growth.

According to AstraZeneca’s estimates, slightly more than 60% of NSCLC patients areDiagnosisfor early-stage (Stage I–III) disease.Approximately 25% of patients with EGFR-mutant non-small cell lung cancer (NSCLC) present with brain metastases at diagnosis, with the incidence rising to around 40% within two years of diagnosis. The presence of brain metastases typically reduces median survival to less than 8 months.

Tagrisso is a third-generation irreversible EGFR-TKI that can overcome resistance to first- and second-generation EGFR-TKIs, including Roche/Astellas Tarceva (erlotinib), AstraZeneca Iressa (gefitinib), and Boehringer Ingelheim Gilotrif (afatinib).

Tagrisso inhibits EGFR sensitizing mutations and the EGFR T790M resistance mutation, demonstrating clinical activity against central nervous system metastases. To date, Tagrisso 40 mg and 80 mg once-daily oral tablets have been approved in 80 countries (including the United States, Japan, China, and the European Union) for first-line treatment of EGFR-mutated advanced NSCLC, and in 87 countries (including the United States, Japan, China, and the European Union) for second-line treatment of patients with EGFR T790M mutation-positive advanced NSCLC.

Currently, AstraZeneca is also developing Tagrisso for adjuvant therapy (ADAURA study), locally advanced unresectable disease (LAURA study), in combination with chemotherapy for metastatic disease (FLAURA2), and in combination with potential new drugs to address resistance to EGFR TKIs (SAVANNAH study, ORCHARD study). (Bioon.com)

Original source:Tagrisso Phase III ADAURA trial will be unblinded early after overwhelming efficacy in the adjuvant treatment of patients with EGFR-mutated lung cancer