Post operative chemotherapy is recommended in patients with NSCLC with stages II to IIIA. EGFR mutations are quite common at NSCLC and drive some of the therapeutic decisions particularly those with EGFR predominant related pathology.
Osimertinib, a third-generation oral EGFR-TKI, potently and selectively inhibits both EGFR-TKI sensitizing and EGFR p.Thr790Met resistance mutations.
In patients with resected disease, the main challenge is to increase free survival rate. The current study is a phase 3, randomized trial which actually assessed the efficacy and safety of osimertinib as compared with placebo in patients with completely resected stage IB to IIIA NSCLC. All patients were EGFR mutation–positive and received adjuvant chemotherapy, according to physician and patient choice.
682 patients were randomized. 339 received osimertinib g and 343 placebo. Most of them were females, with mean age 64 years old, approximately 75% non smokers, with adenocarcinoma, and with equal distribution among the three stages, IB, II and IIIA. 60% received adjuvant chemotherapy, 90% underwent lobectomy.
At 24 months, a statistical significant difference was observed in terms of being alive and disease free. 90% of the patients of the patients with stage II to IIIA disease in the osimertinib group vs 44% of those in the placebo group were alive and disease-free. Interestingly, in the overall population at 24 months 98% in the osimertinib group vs 85% in the placebo group were alive and did not have central nervous system disease. Finally, 29 patients died (9 in the osimertinib group and 20 in the placebo group). No severe adverse events were reported.
- The main message from this study is that patients with resected EGFR mutation–positive NSCLC who received osimertinib had significantly longer disease-free survival than those who received placebo.
- EGFR mutations are considered as critical ones for the post operative adjuvant chemotherapy.