AstraZeneca announced yesterday that the U.S. Food and Drug Administration (FDA) has approved its epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, Tagrisso (osimertinib), for the treatment of adult patients with locally advanced, unresectable (stage III) non-small cell lung cancer (NSCLC) who have not experienced disease progression during or after concurrent or consecutive platinum-based chemotherapy and radiotherapy (CRT), and whose tumors are detected by an FDA-approved test to have an EGFR exon 19 deletion or exon 21L858R mutation.
This approval is based on data from the randomized, double-blind, placebo-controlled phase 3 LAURA trial (ClinicalTrials.gov identifier: NCT03521154), which evaluated the efficacy and safety of osimertinib in 216 patients with locally advanced, unresectable, stage III EGFR mutation-positive NSCLC who had not experienced disease progression after clinical radiotherapy (CRT).
Students were randomized in a 2:1 ratio to receive osimertinib 80 mg once daily or placebo within 6 weeks after completion of CRT until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS).
Results showed that, compared with placebo, osimertinib treatment reduced the risk of disease progression or death by 84% (hazard ratio [HR], 0.16; 95% CI, 0.10–0.24; P < .001). The median progression-free survival (PFS) was 39.1 months (95% CI, 31.5, not estimable) in the osimertinib group and 5.6 months (95% CI, 3.7–7.4) in the placebo group.
Although overall survival (OS) data were immature at the time of analysis, no trend toward impairment was observed. According to AstraZeneca, the trial will continue to evaluate OS as a secondary endpoint.
The most common adverse events reported during the trial were lymphopenia, leukopenia, interstitial lung disease/pneumonia, thrombocytopenia, neutropenia, rash, diarrhea, nail poisoning, musculoskeletal pain, cough, and COVID-19.
"The approval of Tagrisso for patients with unresectable stage III EGFR-mutant non-small cell lung cancer addresses a pressing need for targeted therapy in patients with these mutations who have never previously had access to it," said Dave Fredrickson, Executive Vice President of AstraZeneca's Oncology division. "Results from the LAURA trial demonstrated the powerful impact Tagrisso can have as a backbone therapy for this disease, and with this approval, patients at all stages of EGFR-mutant non-small cell lung cancer can now benefit."
In addition to this new indication, Tagrisso is also indicated for:
1) Adjuvant therapy in adult patients with non-small cell lung cancer (NSCLC) who have undergone tumor resection and whose tumors have EGFR exon 19 deletion or exon 21L858R mutation, as determined by an FDA-approved trial;
2) First-line treatment in adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletion or exon 21L858R mutation, as determined by an FDA-approved test;
3) First-line treatment in adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have EGFR exon 19 deletion or exon 21L858R mutation, in combination with pemetrexed and platinum-based chemotherapy, as determined by an FDA-approved test; and
4) First-line treatment in adult patients with metastatic EGFR T790M mutation-positive non-small cell lung cancer (NSCLC) whose disease has progressed during or after treatment with an EGFR tyrosine kinase inhibitor, as determined by an FDA-approved trial.
