AstraZeneca’s Tagrisso (Osimertinib) Receives Approval in India for Adjuvant Treatment of Early-Stage EGFR-Mutated NSCLC

March 11, 2021 News /Bio ValleyBIOON/ --AstraZeneca(AstraZeneca) India recently announced that the targeted anticancer drug Tagrisso (Chinese brand name: Taisisha; generic name: osimertinib) has been approved in India for use in patients with non-small cell lung cancer (NSCLC) whose tumors harbor epidermal growth factor receptor (EGFR) mutations.TumorAdjuvant Therapy After Complete Resection.

Lung cancer is a highly aggressive and devastating disease. The rising mortality rate from lung cancer is attributed to the fact that nearly 80%–90% of cases are detected and diagnosed at advanced stages, when the five-year survival rate is less than 5%. Early detection before lung cancer spreads to other parts of the bodyDiagnosisand treatment is critically important. However, even when eligible patients receive optimal treatment in the early stages, such as surgery and postoperative chemotherapy, more than half of them experience disease/cancer recurrence within five years. This is primarily attributed to the tendency of cancer to recur and the limited progress in the treatment of early-stage lung cancer. This indicates that the need for patient management remains unmet in efforts to improve patient survival rates.

Tagrisso is a once-daily oral tablet for the treatment ofTumorPatients with EGFR mutations (EGFRm) who have undergone surgical resection for lung cancer. In the phase 3 ADAURA trial for early-stage lung cancerClinical TrialIn China, Tagrisso used as adjuvant therapy reduced the risk of cancer recurrence by nearly 83%. Tagrisso is the first targeted oral therapy to demonstrate such a significant benefit in disease-free survival in EGFRm-positive early-stage lung cancer. The spread of cancer cells to organs such as the brain is one of the important reasons for the recurrence of early-stage lung cancer. Tagrisso has been proven to reduce the likelihood of cancer spreading to the brain and other distant organs.

Notably, the ADAURA trial was the first global clinical trial to demonstrate statistically significant and clinically meaningful benefits of an EGFR inhibitor in the adjuvant treatment of lung cancer. The results provided the first confirmation that an EGFR inhibitor has the potential to alter the course of early-stage EGFR-mutated lung cancer and offer patients hope for a cure.

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

The primary results of this study were published in The New England Journal of Medicine in September 2020. The results showed that: (1) In patients with stage II and IIIA EGFR-mutated non-small cell lung cancer (EGFRm NSCLC), adjuvant therapy with Tagrisso reduced the risk of disease recurrence or death by 83% (HR=0.17; 95% CI: 0.12–0.23; p<0.0001). (2) In the overall study population (patients with stage IB/II/IIIA disease), adjuvant therapy with Tagrisso reduced the risk of disease recurrence or death by 80% (HR=0.20; 95% CI: 0.15, 0.27; p<0.0001). As demonstrated in the pre-specified exploratory analysis, there was a clinically meaningful improvement in central nervous system (CNS) disease-free survival (DFS) compared with placebo.

Based on the unprecedented efficacy results from the ADAURA study, the United StatesFDAApproved Tagrisso in December 2020 as an adjuvant (postoperative) therapy for the treatment of patients who have undergone complete resection with curative intentTumorAdult patients with early-stage (Stage IB/II/IIIA) EGFR-mutated NSCLC who have undergone resection.

In January this year, AstraZeneca at the 21st World Conference on Lung Cancer (WCLC) 2020, hosted by the International Association for the Study of Lung Cancer, onlineMeetingResults from an exploratory analysis of the ADAURA study were announced. The data demonstrated that adjuvant Tagrisso significantly prolonged disease-free survival (DFS) in patients with EGFR mutation-positive non-small cell lung cancer (NSCLC), regardless of prior adjuvant chemotherapy status or disease stage. In this exploratory analysis of the overall study population, adjuvant Tagrisso reduced the risk of disease recurrence or death by 84% in patients who had previously received adjuvant chemotherapy (HR=0.16; 95% CI: 0.10–0.26) and by 77% in those who had not previously received adjuvant chemotherapy (HR=0.23; 95% CI: 0.13–0.40). The DFS benefit was consistent across all disease stages. Furthermore, a separate exploratory post-hoc analysis of patient-reported outcomes from the ADAURA study indicated that patients treated with Tagrisso maintained their quality of life, with no clinically meaningful differences observed between the Tagrisso and placebo groups in terms of physical or mental health.

Tagrisso is a third-generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) capable of overcoming resistance to first- and second-generation EGFR-TKIs, including Roche/Astellas Tarceva, AstraZeneca Iressa, 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 multiple countries (including the United States, Japan, China, and the European Union) for first-line treatment of EGFR-mutated advanced NSCLC, and in multiple countries (including the United States, Japan, China, and the European Union) for second-line treatment of patients with EGFR T790M mutation-positive advanced NSCLC. Furthermore, in the United States and several other countries, Tagrisso is also approved: as an adjuvant (postoperative) therapy for the treatment of patients who have undergone complete resection with curative intentTumorAdult patients with early-stage (Stage IB/II/IIIA) EGFRm NSCLC who have undergone resection.

Currently, AstraZeneca is developing Tagrisso for 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: AstraZeneca receives marketing authorisation for Tagrisso (Osimertinib) for adjuvant treatment of EGFRm Non-Small Cell Lung Cancer (NSCLC) in India