On May 16, 2023 Astrazeneca reported Positive high-level results from the FLAURA2 Phase III trial showed Tagrisso (osimertinib) in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to Tagrisso alone for patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) (Press release, AstraZeneca, MAY 17, 2023, View Source [SID1234631785]).

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Safety results and discontinuation rates due to adverse events were consistent with the established profiles of each medicine. At the time of this analysis, the overall survival (OS) data were immature and will be formally assessed at a subsequent analysis.

Each year, there are an estimated 2.2 million people diagnosed with lung cancer globally with 80-85% of patients diagnosed with NSCLC, the most common form of lung cancer.1-3 Approximately 70% of people are diagnosed with advanced NSCLC. Additionally, about 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.4-6

Pasi A. Jänne, MD, PhD, medical oncologist at Dana-Farber Cancer Institute and principal investigator for the FLAURA2 trial, said: "As the global standard of care for EGFR-mutated non-small cell lung cancer, osimertinib monotherapy has transformed the treatment landscape allowing many patients the opportunity to achieve improved survival. FLAURA2 provides compelling evidence that the addition of chemotherapy to osimertinib can provide a new option for patients and clinicians that further improves outcomes compared to osimertinib alone and as such, can further delay treatment resistance and disease progression."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "These significant FLAURA2 results show Tagrisso has the potential to offer patients in the first-line setting a new treatment option that can extend the time they live without their disease progressing. This meaningfully builds on successive trials which have demonstrated improved clinical benefit with Tagrisso in patients with EGFR-mutated lung cancer."​

The data will be presented at a forthcoming medical meeting and shared with global health authorities.

These results add to the extensive body of evidence for Tagrisso in EGFRm NSCLC, which has improved patient outcomes in both early-stage disease in the ADAURA Phase III trial and late-stage disease in the FLAURA Phase III trial. Tagrisso has also shown proven clinical activity in treating central nervous system (CNS) metastases across settings.

As part of AstraZeneca’s ongoing commitment to treating patients as early as possible in lung cancer, Tagrisso is also being investigated in unresectable NSCLC in the pivotal LAURA Phase III trial, with results expected later this year.

Notes

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.1 Lung cancer is broadly split into NSCLC and small cell lung cancer.2 The majority of all NSCLC patients are diagnosed with advanced disease.7

Patients with EGFRm NSCLC are particularly sensitive to treatment with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) which blocks the cell-signaling pathways that drive the growth of tumour cells.8

FLAURA2
FLAURA2 is a randomised, open-label, multi-centre, global Phase III trial in the 1st-line treatment of 586 patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) EGFRm NSCLC. Patients were treated with Tagrisso 80mg once daily oral tablets in combination with chemotherapy (pemetrexed (500mg/m2) plus cisplatin (75mg/m2) or carboplatin (AUC5)) every three weeks for four cycles, followed by Tagrisso with pemetrexed maintenance every three weeks.

The trial was enrolled in more than 150 centres across more than 20 countries, including in the US, Europe, South America and Asia. This is the final analysis of the primary endpoint of PFS. The trial is ongoing and will continue to assess the secondary endpoint of OS.

Tagrisso
Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against CNS metastases. AstraZeneca continues to explore Tagrisso as a treatment for patients across multiple stages of EGFRm NSCLC.

Tagrisso is approved as monotherapy in more than 100 countries including in the US, EU, China and Japan. These include for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC, locally advanced or metastatic EGFR T790M mutation-positive NSCLC, and adjuvant treatment of early-stage (IB, II and IIIA) EGFRm NSCLC, where Tagrisso recently demonstrated a statistically significant and clinically meaningful OS benefit.

In addition to investigating Tagrisso and chemotherapy in late-stage disease (FLAURA2), AstraZeneca has several ongoing Phase III trials focused on earlier stages of lung cancer. Tagrisso is being tested in the neoadjuvant resectable setting (NeoADAURA), in the Stage IA2-IA3 adjuvant resectable setting (ADAURA2), and in the Stage III locally advanced unresectable setting (LAURA).

The Company is also researching ways to address tumour mechanisms of resistance through the SAVANNAH and ORCHARD Phase II trials, and the SAFFRON Phase III trial, which test Tagrisso given concomitantly with savolitinib, an oral, potent and highly selective MET TKI, as well as other potential new medicines.