FDA designates AstraZeneca's Tagrisso breakthrough therapy in first-line, EGFR-mutated lung cancer

AstraZeneca announced Monday that the FDA granted breakthrough therapy status for Tagrisso (osimertinib) for the first-line treatment of patients with metastatic, EGFR-positive non-small-cell lung cancer (NSCLC). Sean Bohen, chief medical officer at AstraZeneca, said the designation "acknowledges not only Tagrisso's potential as a first-line standard of care in advanced EGFR mutation-positive NSCLC, but also the significant need for improved clinical outcomes in this disease."

According to the company, the designation follows positive results from the Phase III FLAURA trial, evaluating Tagrisso against current standard EGFR tyrosine kinase inhibitor (TKI) therapy with either AstraZeneca's Iressa (gefitinib) or with erlotinib, which Roche and Astellas market as Tarceva, in 556 previously-untreated patients with locally-advanced or metastatic EGFR-mutation-positive NSCLC. 

AstraZeneca said Tagrisso was associated with significantly improved progression-free survival (PFS), with patients achieving median PFS of 18.9 months, compared with 10.2 months for those receiving standard TKI therapy. "Improvements were seen in all pre-specified subgroups, including patients with and without brain metastases," the company stated, adding that Tagrisso's safety profile was also "consistent with previous experience." 

FirstWord reports in this therapy area - KOL Insight Non Small Cell Lung Cancer (NSCLC): Find out how KOLs expect the market to evolve, which pipeline treatments are most promising, and which clinical trials will shape treatment decisions. Learn more. 

UBS analyst Jack Scannell suggested the breakthrough therapy designation "means we may see sales accelerating in [the fourth quarter] from off-label usage," but that "it is unlikely to increase use in the long run." He added that consensus forecasts are for Tagrisso revenues to reach $3.1 billion in 2022, out of total sales of $29.3 billion. Meanwhile, analysts at HSBC commented "we view AstraZeneca's pivot towards oncology as high risk, given both the highly concentrated portfolio and several clinical failures of key pipeline assets." In July, AstraZeneca announced initial results from the Phase III MYSTIC trial, showing that the combination of its PD-L1 inhibitor Imfinzi (durvalumab) plus the CTLA-4 inhibitor tremelimumab failed to improve PFS versus platinum-based standard chemotherapy in previously-untreated patients with metastatic NSCLC. 

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

For additional analysis, see Spotlight On Interview: AstraZeneca strikes back.

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