medwireNews: The third-generation tyrosine kinase inhibitor (TKI) osimertinib significantly improves outcomes relative to platinum-based chemotherapy plus pemetrexed in advanced non-small-cell lung cancer (NSCLC) patients who have acquired the epidermal growth factor receptor (EGFR) T790M mutation after initial treatment with an EGFR TKI, show the AURA3 results.
The phase III trial findings were simultaneously presented at the IASLC 17th World Conference on Lung Cancer, held in Vienna, Austria, and published in The New England Journal of Medicine.
Progression-free survival (PFS) was a median of 10.1 months for the 279 patients with locally advanced or metastatic disease who were randomly assigned to receive oral osimertinib (80 mg/day). This was significantly longer than the 4.4 months observed for the 140 participants given either carboplatin (target area under the curve 5 mg/mL per min) or cisplatin (75 mg/m2) plus pemetrexed (500 mg/m2), equating to a hazard ratio (HR), after accounting for Asian and non-Asian (around 65% in either arm) ethnicity, of 0.30.
The PFS advantage accorded by osimertinib was observed in all prespecified subgroups, including in patients with central nervous system metastases. In this subgroup, median PFS was 8.5 months for participants given osimertinib and 4.2 months for those given chemotherapy (HR=0.32).
Osimertinib-treated participants also had a significantly higher objective response rate than those who received chemotherapy, at 71% and 31%, respectively. And the median duration of response was longer in the osimertinib treatment arm, at 9.7 months compared with 4.1 months for the chemotherapy group.
Lead author Tony Mok, from the Chinese University of Hong Kong, and colleagues note that the outcomes of this phase III trial are “in line with results of the phase 1/2 AURA and AURA2 studies.”
The safety profile of osimertinib was also consistent with previous reports, and differed from that of chemotherapy, the team writes. Specifically, the incidence of grade 3 or worse adverse events was lower in osimertinib- than chemotherapy-treated patients (23 vs 47%), as was the rate of toxicity-related discontinuation (7 vs 10%).
Study author Vassiliki Papadimitrakopoulou, from The University of Texas MD Anderson Cancer Center in Houston, USA, told the press in Vienna that in light of the statistically superior and clinically meaningful efficacy of osimertinib over chemotherapy, the TKI could be considered the “standard of care” for this patient population.
She emphasized, however, that to deliver osimertinib, one needs to know whether or not the T790M mutation is present, which “should provide the impetus for us to test either the tumour or plasma.”
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