Third-Generation EGFR-TKI Superior to Standard Inhibitors in Advanced NSCLC

Submitted by onc_editor on Fri, 01/12/2018 - 14:18

A recent analysis found a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) to offer superior efficacy compared with standard EGFR-TKIs in the first-line setting for EGFR-positive advanced non-small cell lung cancer (NSCLC), published in The New England Journal of Medicine (online January 11, 2018; doi:10.1056/NEJMoa1713137).

Osimertinib is an oral, irreversible EGFR-TKI that is designed to inhibit both EGFR-TKI-sensitizing and EGFR T790M resistance mutations.

Jean-Charles Soria, MD, PhD, professor of medicine and medical oncology, South-Paris University (France), and colleagues conducted a study to compare osimertinib with standard EGFR-TKIs in patients with previously untreated, EGFR mutation-positive advanced NSCLC. The double-blind, phase III, randomly assigned 556 patients (1:1) to receive either osimertinib (80 mg, once daily) or a standard EGFR-TKI (gefitinib, 250 mg, once daily or erlotinib, 150 mg, once daily).

All patients exhibited either exon 19 deletion or L858R. The primary endpoint of the study was investigator-assessed progression-free survival (PFS).

Results of the study showed that the median PFS was significantly longer with osimertinib than with standard EGFR-TKIs (18.9 vs 10.2 months, respectively; HR, 0.46; 95% CI, 0.37-0.57; P < .001).

Additionally, researchers reported that while the objective response rate was similar in the two groups (80% vs 76%, respectively; odds ratio, 1.27; 95% CI, 0.85-1.90; P = .24), the median duration of response favored osimertinib (17.2 months, 95% CI, 13.8-22.0) over standard EGFR-TKIs (8.5 months, 95% CI, 7.3-9.8).

Furthermore, the data on overall survival were reportedly immature at the interim analysis (25% maturity). But the survival rate at 18 months was 83% (95% CI, 78%-87%) with osimertinib and 71% (95% CI, 65%-76%) with standard EGFR-TKIs, (HR, 0.63; 95% CI, 0.45-0.88; P = .007). This difference in survival rates was deemed not significant in the interim analysis.

Adverse events of grade 3 or higher were less frequent with osimertinib than with standard EGFR-TKIs (34% vs 45%, respectively).

Results of the study led Dr. Soria and colleagues to conclude that, “Osimertinib showed efficacy superior to that of standard EGFR-TKIs in the first-line treatment of EGFR mutation–positive advanced NSCLC, with a similar safety profile and lower rates of serious adverse events.”—Zachary Bessette