Tagrisso Reduces Risk of CNS Recurrence or Death by 82% in Adjuvant Treatment of Early-Stage EGFRm NSCLC

September 20, 2020 /BioValleyBIOON/ --AstraZeneca(AstraZeneca) recently announced positive results from the exploratory analysis of the Phase III ADAURA study of the targeted anticancer drug Tagrisso (Chinese brand name: Tai Rui Sha; generic name: osimertinib) at the 2020 European Society for Medical Oncology (ESMO) Virtual Congress. The data showed that, among patients who had received curative completeTumorIn patients with early-stage (Stage IB/II/IIIA) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) following resection, Tagrisso demonstrated a clinically meaningful improvement in central nervous system (CNS) disease-free survival (DFS) when used as adjuvant therapy. These data reinforce the established clinical efficacy of Tagrisso in treating CNS metastases.

Although up to 30% of NSCLC patients may beDiagnosisThe disease is at a sufficiently early stage with the potential for curative surgery, but disease recurrence remains common among patients with early-stage lung cancer. WhenTumorCentral nervous system (CNS) recurrence is a common complication of EGFR-mutated non-small cell lung cancer (EGFRm-NSCLC) when it spreads to the brain, and the prognosis for these patients is particularly poor.

Pre-specified analyses presented at the meeting indicated that, compared with placebo,Fewer patients receiving adjuvant Tagrisso therapy experienced recurrence events or death (11% vs. 46%).Among patients with cancer recurrence, 38% of those treated with Tagrisso experienced metastatic recurrence, compared with 61% of those treated with placebo. Furthermore,Tagrisso demonstrated an 82% reduction in the risk of CNS recurrence or death (HR=0.18; 95% CI: 0.10-0.33, p<0.0001). The median CNS DFS was not reached in either treatment group.

A post hoc analysis showed that among patients who had not experienced other types of recurrence, those treated with TagrissoThe estimated probability of brain disease recurrence observed at 18 months was <1%, compared with 9% in patients receiving placebo.. In terms of the primary endpoint of DFS in patients with stage II and IIIA disease,Tagrisso adjuvant therapy reduced the risk of disease recurrence or death by 83% (HR=0.17; 95% CI: 0.12-0.23; p<0.0001).

In this study, the safety and tolerability profile of Tagrisso was consistent with that observed in prior trials in metastatic EGFR-mutant NSCLC. According to investigator assessment, 10% of patients in the Tagrisso group experienced grade 3 or higher adverse events, compared with 3% in the placebo group.

It is worth noting that the ADAURA trial was the first global study to demonstrate statistically significant and clinically meaningful benefits of an EGFR inhibitor in the adjuvant treatment of lung cancer.Clinical Trial. The results provide the first proof that:An EGFR inhibitor can alter the course of early-stage EGFR-mutant lung cancer and offer hope for a cure to patients.

Dr. Masahiro Tsuboi, Chief Investigator of the ADAURA study, stated: “It is time to change the paradigm of treatment cessation after surgery for early-stage EGFR-mutated lung cancer, as recurrence rates remain high, even following adjuvant chemotherapy. These new data demonstrate that Tagrisso, when used as postoperative adjuvant therapy, is associated with low recurrence rates, particularly in the brain, along with a significant disease-free survival benefit. These findings clearly indicate that Tagrisso provides patients with more time free from disease.”

AstraZenecaTumorJosé Baselga, Executive Vice President of Research and Development, stated, “Once lung cancer spreads to the brain, the outcomes are typically devastating. We are now seeing that, due to Tagrisso’s ability to cross the blood-brain barrier, its efficacy in treating metastatic progression in brain tissue is expanding. These compelling new data demonstrate that Tagrisso can prevent brain metastases in patients with early-stage disease, further proving that this drug is truly transformative for patients with EGFR-mutated (EGFRm) lung cancer. Tagrisso should become the standard of care in the adjuvant setting, just as it is for patients with metastatic disease worldwide.”

Lung cancer is a devastating disease, although up to 30% of NSCLC patients mayDiagnosisearly enough and with the potential to undergo curative surgical resection, but disease recurrence is common in early-stage disease; nearly half of patients diagnosed at stage IB and more than three-quarters of those diagnosed at stage IIIA will experience recurrence within 5 years.

Tagrisso is an oral, small-molecule, third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that has been approved in multiple countries and regions worldwide, including the United States, Japan, China, and the European Union, for: (1) first-line treatment of patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC); and (2) second-line treatment of patients with locally advanced or metastatic NSCLC harboring EGFR T790M mutation-positive status.

Currently, Tagrisso has not been approved by any country for adjuvant therapy. This July, the United StatesFDAGranting of Breakthrough Therapy Designation (BTD) to Tagrisso for use as postoperative adjuvant therapy in patients with early-stage (Stage IB/II/IIIA) EGFRm NSCLC who have undergone curative complete tumor resection. This BTD is based on the unprecedented efficacy results from the Phase III ADAURA study. Data show that, in patients who received completeTumorIn patients with early-stage (Stage IB/II/IIIA) EGFR-mutated non-small cell lung cancer (EGFRm-NSCLC) who underwent resection, Tagrisso used as postoperative adjuvant therapy significantly prolonged disease-free survival (DFS) and reduced the risk of disease recurrence or death by 83%.

Based on the results of the ADAURA study, AstraZeneca has been advancing its regulatory submission plans for Tagrisso as adjuvant therapy for EGFR-mutated non-small cell lung cancer (EGFRm NSCLC). Currently, AstraZeneca is also progressing other studies on Tagrisso, including: treatment of locally advanced unresectable disease (LAURA study), combination with chemotherapy for metastatic disease (FLAURA2), and combination with potential new drugs to address resistance to EGFR TKIs (SAVANNAH study, ORCHARD study). (Bioon.com)

Original Source: Tagrisso reduced the risk of disease recurrence in the brain by 82% in the adjuvant treatment of early-stage EGFR-mutated lung cancer