Overall Survival Improved with Adjuvant Osimertinib in Resected EGFR-Mutated NSCLC

1. The 5-year overall survival had a hazard ratio of 0.49, and this benefit was generally consistent across subgroups (stage, EGFR mutation, race) as well as adjuvant chemotherapy status

2. Safety was consistent with prior analysis and no new adverse events were reported.

Evidence Rating Level: 1 (Excellent)  

Study Rundown: Resectable non-small cell lung cancer (NSCLC) was traditionally treated with surgical resection followed by adjuvant chemotherapy. However, the efficacy of adjuvant chemotherapy was limited, especially in patients with EGFR-mutated disease, who have a higher risk of recurrence. Osimertinib, a targeted treatment, has shown significant disease-free survival benefits in patients with EGFR-mutated NSCLC after complete tumour resection, however, evidence of overall survival benefit was still lacking in the context of adjuvant therapy. This study was a final analysis of a phase three trial that investigated the outcomes of osimertinib in EGFR-mutated NSCLC. The overarching primary endpoint was disease-free survival (DFS) and secondary endpoints included overall survival (OS) and safety, but this study focused on the final analysis of the OS. The 5-year OS in the overall population was 88% (95%CI, 83 to 91) in the osimertinib group vs 78% (95%CI, 73 to 82) in the placebo group, with an HR 0.49 (95%CI, 0.34 to 0.70, P<0.001). The OS benefit with adjuvant osimertinib was generally consistent across subgroups (stage, EGFR mutation, race) as well as adjuvant chemotherapy status. HR for the first subsequent treatment or death in the overall population was 0.28 (95%CI, 0.22 to 0.35). An updated safety analysis was carried out and was consistent with prior analysis, with no new adverse events of special interest reported. The strengths of this study included its comprehensive analysis and methodology, and the limitations included the potential underrepresentation of racial and ethnic subgroups, Overall, in patients with EGFR-mutated stage IB-IIIA NSCLC who underwent complete tumour resection, adjuvant osimertinib demonstrated an improvement in overall survival and will likely shift the treatment paradigm of early-stage EGFR-mutated NSCLC.

Click to read the study in NEJM

Relevant Reading: Adjuvant Osimertinib for Resected EGFR-Mutated Stage IB-IIIA Non–Small-Cell Lung Cancer: Updated Results From the Phase III Randomized ADAURA Trial

In-Depth [randomized controlled trial]: This international, phase 3, double-blind, placebo-controlled trial investigated postsurgical adults with stage IB-IIIA NSCLC with a confirmed EGFR mutation who were randomly assigned to oral osimertinib (339 patients) or placebo (343). Baseline characteristics were balanced between the groups. Analysis was split between patients with stage II-IIIA and the overall population (stage IB-IIIA). The median duration of follow-up in patients with stage II to IIIA disease was 59.9 months in the osimertinib group and 56.2 in the placebo group, whereas median follow-up in the overall population was 60.4 months in the osimertinib group and 59.4 months in the placebo group. The 5-year overall survival in the stage II-IIIA subpopulation was 85% (95%CI, 79 to 89) in the osimertinib group vs 73% (95%CI, 66 to 78) in the placebo group, with an HR 0.49 (95%CI, 0.33 to 0.73, P<0.001) and in the overall population was 88% (95%CI, 83 to 91) in the osimertinib group vs 78% (95%CI, 73 to 82) in the placebo group, with an HR 0.49 (95%CI, 0.34 to 0.70, P<0.001). The overall survival benefit with adjuvant osimertinib was generally consistent across subgroups (stage, EGFR mutation, race) as well as adjuvant chemotherapy status. HR for the first subsequent treatment or death in the overall population was 0.28 (95%CI, 0.22 to 0.35). An updated safety analysis was done and was consistent with prior analysis (mainly low-grade adverse events over an extended treatment duration), with no new adverse events of special interest reported. Overall, in patients with EGFR-mutated stage IB-IIIA NSCLC who underwent complete tumour resection, adjuvant osimertinib demonstrated an improvement in overall survival.

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