The New England Journal of MedicineOsimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC

Evidence suggests that the addition of chemotherapy may extend the benefits of EGFR-TKI therapy — does this trial prove the theory?

A recent phase 3, international, open-label trial investigated the efficacy of osimertinib, a third-generation epidermal growth factor receptor–tyrosine kinase inhibitor (EGFR-TKI), with and without chemotherapy in patients with EGFR-mutated advanced non–small-cell lung cancer (NSCLC). The study demonstrated a significant improvement in progression-free survival with the combination of osimertinib and chemotherapy.

Study Design

• The trial involved 557 patients with EGFR-mutated (exon 19 deletion or L858R mutation) advanced NSCLC who had not previously received treatment for advanced disease.
• Patients were randomly assigned to receive osimertinib (80 mg once daily) with chemotherapy (pemetrexed [500 mg per square meter of body-surface area] plus either cisplatin [75 mg per square meter] or carboplatin [pharmacologically guided dose]) or osimertinib monotherapy (80 mg once daily).
• The primary end point was investigator-assessed progression-free survival.

Key Findings

• Progression-free survival was significantly longer in the osimertinib–chemotherapy group than in the osimertinib group (hazard ratio for disease progression or death, 0.62; 95% CI, 0.49 to 0.79; P<0.001).
• At 24 months, 57% of the patients in the osimertinib–chemotherapy group and 41% of those in the osimertinib group were alive and progression-free.
• An objective (complete or partial) response was observed in 83% of the patients in the osimertinib–chemotherapy group and in 76% of those in the osimertinib group.
• The median response duration was longer in the osimertinib–chemotherapy group (24.0 months) compared to the osimertinib group (15.3 months).
• The incidence of grade 3 or higher adverse events from any cause was higher with the combination than with monotherapy.

The rate of new lung cancer cases has fallen an average of 2 percent a year over the last 10 years.

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