The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for osimertinib for the 1st-line treatment of patients with metastatic epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC).

The FDA granted the BTD based on data from the Phase III FLAURA trial of osimertinib versus standard-of-care EGFR tyrosine kinase inhibitor (TKI) therapy in previously-untreated patients with locally-advanced or metastatic EGFR mutation-positive NSCLC.

In the trial, median progression-free survival was 18.9 months for osimertinib compared with 10.2 months for EGFR-TKIs (erlotinib or gefitinib).

Improvements were seen in all pre-specified subgroups, including patients with and without brain metastases.

Approximately 10% to 15% of lung cancer patients in the US and Europe, and 30% to 40% of patients in Asia have epidermal growth factor receptor mutation-positive (EGFRm) NSCLC.

These patients are particularly sensitive to treatment with currently-available EGFR tyrosine kinase inhibitors (TKIs), which block the cell signalling pathways that drive the growth of tumour cells.

However, tumours almost always develop resistance to EGFR-TKI treatment, leading to disease progression.

Approximately half of patients develop resistance to approved EGFR-TKIs, such as gefitinib and erlotinib, due to the resistance mutation, EGFR T790M.

Osimertinib targets this secondary mutation that leads to disease progression.

The safety profile of osimertinib was consistent with previous experience.

In patients treated with osimertinib, the most common AEs were diarrhea (58%, any grade [2% Grade ≥3]) and dry skin (32%, any grade [<1% Grade ≥3]), and in the comparator arm group the most common AEs were diarrhea (57%, any grade [2% Grade ≥3]) and dermatitis acneiform (48%, any grade [5% Grade ≥3]).

Of the patients on osimertinib, 34% had a Grade ≥3 AE, compared to 45% in the comparator arm, and 13% of patients on osimertinib had an AE leading to treatment discontinuation compared to 18% in the comparator arm.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “The Breakthrough Designation acknowledges not only TAGRISSO’s potential as a 1st-line standard of care in advanced EGFR mutation-positive NSCLC, but also the significant need for improved clinical outcomes in this disease. The results of the FLAURA trial have the potential to redefine clinical expectations and offer new hope for patients who currently have a poor prognosis.”

Osimertinib is currently approved in more than 50 countries, including the US, EU, Japan and China, as 2nd-line treatment for patients with advanced NSCLC who progress following treatment with an EGFR-TKI due to the EGFR T790M resistance mutation.

Once-daily osimertinib tablets are approved by the FDA for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after an EGFR TKI therapy.

It is the first and only approved medicine in the US indicated for NSCLC patients who have tested positive for the EGFR T790M mutation.

Source: BusinessWire