Osimertinib Granted Full Approval by EU for EGFR T790M-Positive NSCLC


Osimertinib has been granted a full approval by the European Union for the treatment of patients with locally advanced or metastatic <em>EGFR T790M&nbsp;</em>mutation-positive non&ndash;small cell lung cancer, regardless of prior treatment with an EGFR TKI.

Sean Bohen, MD, PhD

Sean Bohen, MD, PhD

Osimertinib (Tagrisso) has been granted a full approval by the European Union (EU) for the treatment of patients with locally advanced or metastaticEGFR T790Mmutation-positive non—small cell lung cancer (NSCLC), regardless of prior treatment with an EGFR TKI.

This full approval comes a bit more than a year after osimertinib became the new first medicine to win clearance under the European Commission&rsquo;s expedited process. The FDA in March awarded full approval to AstraZeneca to market the drug in the United States.

&ldquo;The full approval of Tagrisso in the EU is further evidence of our exciting progress in transforming the science of cancer care to deliver life-changing medicines to people most in need,&rdquo; said AstraZeneca chief medical officer Sean Bohen, MD, PhD, said in a statement. &ldquo;Having demonstrated its superiority over chemotherapy inEGFR T790Mmutation-positive non—small cell lung cancer, Tagrisso has the potential to become the new standard of care for patients with this difficult-to-treat form of lung cancer.&rdquo;

Osimertinib is a third-generation, irreversible EGFR tyrosine kinase inhibitor designed to inhibit both EGFR sensitizing andEGFR T790M resistance mutations and to have activity in the central nervous system.

In granting the approval, the EU relied on data from the open-label, phase III AURA3 trial, which demonstrated statistically-significant improvements in progression-free survival (PFS) over standard platinum-based doublet chemotherapy. Median PFS was 10.1 months for osimertinib compared with 4.4 months for standard platinum-based chemotherapy (HR, 0.30; 95% CI, 0.23-0.41;P<.001).

PFS was 8.5 months for patients with CNS metastases in the osimertinib group compared with 4.2 months in the chemotherapy group (HR, 0.32; 95% CI, 0.21-0.49).

Osimertinib produced an objective response rate more than twice that of chemotherapy, 71% vs 31% (odds ratio = 5.39; 95% CI, 3.47-8.48;P<.001). Six-month PFS was 69% with osimertinib compared with 37% with chemotherapy. At 12 months, PFS in the osimertinib arm was more than 4-times greater than in the chemotherapy group (44% vs 10%).

In AURA3, patients were randomly assigned to a 21-day cycle of once-daily 80 mg osimertinib (n = 279) or pemetrexed plus carboplatin or pemetrexed plus cisplatin (n = 140). In the control arm, patients were assigned to 500 mg/m2pemetrexed, 5 AUC carboplatin, and 75 mg/m2cisplatin.

The median age of patients in the osimertinib arm was 62 years compared with 63 years in the chemotherapy cohort. Nearly all the patients had metastatic disease, and about one-third of patients in both groups had CNS metastases. Approximately 60% of the participants had been treated with gefitinib (Iressa), 35% had been treated with erlotinib (Tarceva), and nearly 6% had been prescribed afatinib (Gilotrif).

In the osimertinib group, adverse events (AEs) of any grade reported by >10% of participants included diarrhea (41%), rash (34%), dry skin (23%), and paronychia (22%). In the chemotherapy group, the most common toxicities of any grade were nausea (49%), decreased appetite (36%), constipation (35%), and fatigue (28%).

Osimertinib patients reported fewer grade &ge;3 AEs, 23% vs 47%. The most frequently reported grade &ge;3 events in the chemotherapy arm were neutropenia (12%), anemia (12%), and thrombocytopenia (7%). Incidence of each was less than 1% in the osimertinib group.


Mok TS, Wu YL, Ahn MJ, et al. The AURA3 Investigators. Osimertinib or platinum—pemetrexed in EGFR T790M&ndash;positive lung cancer.N Engl J Med.2017; 376:629-640.

Related Videos
Related Content