India: Osimertinib Granted Breakthrough Designation By FDA For 1st-line Treatment Of Patients With EGFR (Epidermal Growth Factor Receptor) Mutation-Positive Non-Small Cell Lung Cancer (NSCLC)

AstraZeneca announced on 09-October-2017, that the United States Food and Drug Administration (US-FDA) has granted Breakthrough Therapy Designation (BTD) for Osimertinib for the 1st-line treatment of patients with metastatic epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC)¹¹.

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.

BTD is designed to expedite the development and regulatory review of new medicines that are intended to treat a serious condition and have shown encouraging early clinical results, which demonstrate substantial improvement on a clinically-significant endpoint over available medicines and when there is significant unmet medical need.

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 signaling 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 Breakthrough Therapy Designation acknowledges not only Osimertinib'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.

On September 28, 2017, the US National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology were updated to include the use of Osimertinib in the 1st-line treatment of patients with locally-advanced or metastatic EGFR mutation-positive NSCLC. The use of Osimertinib for the 1st-line treatment of patients with locally-advanced or metastatic EGFR mutation-positive NSCLC is not yet FDA approved. However, 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.

About NSCLC

Lung cancer is the leading cause of cancer death among both men and women, accounting for about onequarter of all cancer deaths. Deaths due to lung cancer surpass deaths due to breast, prostate and colorectal cancers combined together. Approximately 10-15% of patients in the US and Europe, and 30-40% of patients in Asia have EGFR-mutated NSCLC. These patients are particularly sensitive to treatment with currently-available EGFR TKIs, which block the cell-signaling 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 the patients develop resistance to approved EGFR TKIs such as Gefitinib and Erlotinib due to the resistance mutation, EGFR T790M. Tagrisso also targets this secondary mutation that leads to disease progression. There is also a need for medicines with improved CNS efficacy, since approximately 25% of patients with EGFR-mutated NSCLC have brain metastases at diagnosis, increasing to approximately 40% within two years of diagnosis.

About Osimertinib

Osimertinib is a third-generation, irreversible EGFR TKI (Tyrokinase Inhibitor) designed to inhibit both EGFRsensitizing and EGFR T790M-resistance mutations, with clinical activity against Central Nervous System (CNS) metastases.

Footnotes

11 https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2017/tagrisso-granted-breakthrough-ther apy-designation-by-us-fda-for-the-1st-line-treatment-of-patients-with-egfr-mutation-positive-non-small-cell-lungcancer- 09102017.html

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