Tagrisso Plus Chemotherapy Reduces Intracranial Progression Risk by 42% in EGFR-Mutated Advanced NSCLC Patients with Baseline Brain Metastases

III Phase Clinical StudyFLAURA2The results showed,59%Patients achieved complete remission of brain tumors while receiving treatment with Tagrisso combined with chemotherapy.

ShanghaiOctober 23, 2023PR Newswire -- Pre-specified exploratory analysis results from the Phase III FLAURA2 clinical trial show that, according to assessments by the Blinded Independent Central Review (BICR), in patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) and baseline brain metastases (accounting for 40% of the total number of patients enrolled in the study), the combination of Tagrisso (osimertinib) and chemotherapy reduced the risk of intracranial progression by 42% compared to Tagrisso monotherapy.

These results were presented as an oral report at the European Society for Medical Oncology Annual Meeting (ESMO) (Abstract #LBA68), held from October 20 to 24 this year in Madrid, Spain.

In these patients, according to the BICR assessment results, compared with osimertinib monotherapy, the combination of osimertinib and chemotherapy reduced the risk of CNS disease progression or death by 42% (hazard ratio [HR]: 0.58; 95% confidence interval [CI] 0.33-1.01). After two years of follow-up, 74% of patients in the osimertinib plus chemotherapy group had not experienced CNS disease progression or death, compared to 54% in the osimertinib monotherapy group. The results also showed that the proportion of patients achieving complete CNS response (CR) was higher in the osimertinib plus chemotherapy group than in the osimertinib monotherapy group (59% vs. 43%).

"FLAURA2 study lead investigator Dr. David Planchard, a thoracic oncologist at the Gustave Roussy Cancer Center, stated: 'Osimertinib has been shown to cross the blood-brain barrier and improve outcomes for lung cancer patients with brain metastases, whose prognosis is typically worse than those without brain metastases. In the FLAURA2 study, more than half of the patients in the osimertinib plus chemotherapy group achieved complete response and intracranial tumor disappearance.'"

Susan Galbraith, Executive Vice President of AstraZeneca and Head of Oncology R&D, stated: "In the FLAURA2 trial, patients with baseline brain metastases achieved meaningful and significant benefits from osimertinib combined with chemotherapy, bringing new hope to patients with brain metastases. These data build on the recent positive results of progression-free survival from the FLAURA2 study, further demonstrating that osimertinib is a cornerstone therapy for EGFRm NSCLC."

The safety of osimertinib combined with chemotherapy is generally manageable and consistent with the established safety profiles of the two drugs. The incidence of adverse events (AEs) was higher in the osimertinib plus chemotherapy group, mainly due to chemotherapy-related adverse events. The discontinuation rate of osimertinib was low in both the experimental and control groups (11% in the osimertinib plus chemotherapy group and 6% in the osimertinib monotherapy group).

In the osimertinib plus chemotherapy group, the median duration of osimertinib treatment was 22.3 months, the median exposure time to platinum-based chemotherapy was 2.8 months, and the median exposure time to pemetrexed was 8.3 months.

Summary of CNS Efficacy in FLAURA2 Study:

Tagrisso plus chemotherapy

(n=118)

Osimertinib Combined with Chemotherapy Group (n=118)

Tagrisso monotherapy

(n=104)

Osimertinib MonotherapyGroup (n=104)

PFS HR (95% CI)

Progression-Free Survival Hazard Ratio (95% CI)

0.58 (0.33-1.01)

Median PFS (months; 95% CI)

Median Progression-Free Survival (Unit: Month;95% CI）

30.2 (28.4-NCⁱⁱ)

27.6 (22.1-NC)

CNS objective response rate, n (%)

CNSObjective Response Rate,n (%)

86 (73)

72 (69)

CR, n (%)

Complete remission,n (%)

70 (59)

45 (43)

Median CNS duration of response (in months; 95% CI)

CNSMedian Duration of Relief (Unit: Month,95% CI）

NRⁱⁱⁱ (23.8-NC)

26.2 (19.4-NC)

i Data cut-off date is2023Year4Month3Day.

ii NC, Incalculable

iii NR, Not reached

In August 2023, the FDA granted breakthrough therapy designation to osimertinib in combination with chemotherapy for the first-line treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC). Earlier this month, based on the recent PFS data from the FLAURA2 Phase III clinical trial presented at the International Association for the Study of Lung Cancer (IASLC)/2023 World Conference on Lung Cancer (WCLC), the U.S. Food and Drug Administration (FDA) granted priority review to osimertinib in combination with chemotherapy for the first-line treatment of adult patients with locally advanced or metastatic EGFR-mutated NSCLC.