For patients with advanced non-small cell lung cancer and a mutation in the epidermal
growth factor receptor (or EGFR), first line treatment is with an EGFR tyrosine kinase
inhibitor (an EGFR-TKI).
Some patients initially have a good response to this treatment but over time the cancer
progresses in most.
In up to 60% of patients who have a recurrence of lung cancer, a point mutation in the gene
coding region T790M has been identified.
The presence of this mutation is associated with reduced binding of the EGFR TKI therapy
to the receptor, leading to less inhibition and to cancer progression.
Osimertinib is an oral, irreversible EGFR-TKI that is selective for both EGFR and T790M
resistance variants with activity against metastases to the central nervous system.
The international, open-label, AURA3 trial included 419 patients with T790M-positive
advanced non-small cell lung cancer, who had progression of cancer after prior treatment
with EGFR-TKI therapy.
144 of the patients (34%) had asymptomatic brain metastases.
Patients were randomized to receive a daily dose of osimertinib or intravenous platinum-pemetrexed
chemotherapy every three weeks for 6 cycles, followed by maintenance pemetrexed.
The primary endpoint was investigator-assessed median progression-free survival, which was
10.1 months in the osimertinib group, as compared with 4.4 months among those treated with IV
chemotherapy.
The hazard ratio, 0.30 was statistically significant.
A subgroup analysis of the patients with CNS metastases showed a median progression-free
survival of 8.5 months in the osimertinib group, as compared with 4.2 months in the
IV chemotherapy group.
Patients in the osimertinib group had diarrhea, rash and dry skin.
Cases of severe myelotoxicity were less common with osimertinib than with IV chemotherapy.
The authors conclude that in patients with T790M-positive advanced non-small cell lung
cancer and prior EGFR-TKI therapy, treatment with osimertinib resulted in significantly
longer progression-free survival than did IV platinum-pemetrexed chemotherapy.
Full trial results are available at NEJM.org.