Editors' ChoiceCancer

Early stage EGFR-mutated lung cancer gets a targeted treatment

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Science Translational Medicine  28 Oct 2020:
Vol. 12, Issue 567, eabf2637
DOI: 10.1126/scitranslmed.abf2637

Abstract

Osimertinib improves disease-free survival for patients with early stage EGFR-mutated non-small cell lung cancer after complete tumor resection.

About 30% of patients with non-small cell lung cancer (NSCLC) present at diagnosis with resectable tumors for which surgery has curative treatment intent. However, recurrence rates are high, and adjuvant chemotherapy only moderately improves survival at 5 years, with only 5% decrease in the risk of death. Currently there are no targeted treatments available in the adjuvant setting after complete tumor resection for patients with NSCLC. Although epidermal growth factor receptor (EGFR) mutations are one of the most common alterations in NSCLC, EGFR inhibitors such as osimertinib are targeted therapies currently approved only for patients with advanced or metastatic NSCLC with EGFR mutations.

Wu et al. report the results of a phase III, double-blinded, placebo-controlled, randomized trial where patients were randomly assigned in a 1:1 ratio to receive either oral osimertinib or placebo. Eligible patients had EGFR-mutated stage IB to IIIA NSCLC, and they could have received prior adjuvant chemotherapy. Endpoints of the study included disease-free survival, overall survival, and safety. Overall, 682 patients were randomized, with 339 patients in the osimertinib group and 343 in the placebo arm. For patients with stage IB to IIIA EGFR-mutated NSCLC, disease-free survival was significantly longer (89% of the patients in the osimertinib group vs 52% in the placebo group were disease-free at 24 months), and central nervous relapses were significantly reduced among those who received osimertinib compared to those who received placebo. Patients in the osimertinib arm had a higher overall rate of grade 3 toxicity (20% vs 13% of patients receiving placebo); however, this was expected and was similar to previously published data.

These findings highlight that patients with early stage EGFR-mutated NSCLC could benefit from adjuvant targeted treatment with osimertinib after surgery with longer disease-free survival and lower recurrence rates. Osimertinib will likely be approved for adjuvant treatment of early stage EGFR-mutated NSCLC.

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