AZ’s Tagrisso plus chemo get fast FDA review for lung cancer

AstraZeneca will hear back from the FDA in the first quarter of next year about its recent filing of Tagrisso in combination with chemotherapy as a first-line treatment for EGFR-positive non-small cell lung cancer (NSCLC).

The US regulator has granted the application a priority review, said AZ this morning, on the back of phase 3 data showing that adding chemo to standard first-line therapy with Tagrisso (osimertinib) improved progression-free survival (PFS), albeit at the expense of a higher side-effect burden.

AZ presented the results of the FLAURA-2 trial at the World Congress on Lung Cancer (WCLC) congress last month, showing that adding chemo to Tagrisso resulted in a 38% improvement in PFS compared to Tagrisso alone.

That equated to an extension of nearly nine months – from 16.7 months to 25.5 – that was described as potentially “practice-changing” by the International Association for the Study of Lung Cancer's (IASLC) president, Heather Wakelee.

AZ’s head of oncology, Susan Galbraith, said this morning that the FLAURA-2 results “reinforce Tagrisso as a backbone of standard of care in first-line EGFR-mutated non-small cell lung cancer.”

She highlighted the effect of the combination on patients whose lung cancer had metastasised to the brain – around 40% of the overall study population – who saw a 53% improvement in PFS, extending it by just over 11 months compared to Tagrisso monotherapy.

“We look forward to working with the FDA on an accelerated timeline to bring this treatment regimen to patients as quickly as possible,” said Galbraith.

Approval of the new regimen could help AZ defend Tagrisso in the face of rising competition in the market for first-line therapies for EGFR-mutated NSCLC, including a challenge from Johnson & Johnson’s bispecific EGFR/MET-targeting antibody Rybrevant (amivantamab).

Rybrevant is currently approved only for a subcategory of EGFR+ NSCLC patients with exon 20 mutations – a niche indication not on Tagrisso’s label – but J&J is working on expanding its use in the first-line setting.

Initially, that involves seeking approval for a combination of Rybrevant and chemo in the exon 20-positive population, but J&J is also running a head-to-head trial of Rybrevant and experimental tyrosine kinase inhibitor lazertinib in a broad EGFR-positive NSCLC population.

Tagrisso is AZ’s top-selling product, adding more than $2.9 billion to its top line in the first half of this year from use as a first-line monotherapy in EGFR-positive advanced NSCLC and as a post-surgery adjuvant therapy for earlier-stage disease.