Posted by Carla Rothaus
Did osimertinib prolong disease-free survival as compared with placebo in the ADAURA trial?
The phase 3, randomized ADAURA trial assessed the efficacy and safety of osimertinib as compared with placebo in patients with completely resected stage IB to IIIA EGFR mutation–positive non–small-cell lung cancer (NSCLC), after adjuvant chemotherapy, according to physician and patient choice. After a planned review by the independent data monitoring committee in April 2020, the committee recommended that the trial be unblinded at a trial level 2 years early because of evidence of an efficacy benefit; the results of this interim analysis were recently reported, based on this recommendation. Read the NEJM Original Article here.
Q: How effective is adjuvant cisplatin-based chemotherapy in patients with resected NSCLC?
A: Approximately 30% of patients with NSCLC present with resectable disease. Postoperative adjuvant cisplatin-based chemotherapy is recommended in patients with completely resected stage II to IIIA disease and — subject to postoperative evaluation to assess benefits and risks — in selected patients with stage IB disease. However, this therapy is associated with only a 16% decrease in the risk of disease recurrence or death; at 5 years, it is associated with a 5% decrease in the risk of death.
Q: What are some of the common oncogenic driver mutations in NSCLC?
A: Epidermal growth factor receptor (EGFR) mutations such as exon 19 deletions (Ex19del) and exon 21 codon p.Leu858Arg (L858R) point mutations are common oncogenic driver mutations in NSCLC. EGFR tyrosine kinase inhibitors (EGFR-TKIs) are the recommended first-line treatment for EGFR mutation–positive advanced NSCLC. The efficacy of EGFR-TKIs in patients with advanced disease led to investigation of their use as an adjuvant treatment for resectable disease.
Morning Report Questions
Q: Did osimertinib prolong disease-free survival as compared with placebo in the ADAURA trial?
A: In the ADAURA trial, patients with resected EGFR mutation–positive NSCLC who received osimertinib had significantly longer disease-free survival than those who received placebo. With respect to the primary end point of disease-free survival, among patients with stage II to IIIA disease, 90% of those in the osimertinib group and 44% of those in the placebo group were alive and disease-free at 24 months (overall hazard ratio for disease recurrence or death, 0.17; 99.06% CI, 0.11 to 0.26; P<0.001). With respect to the key secondary end point of disease-free survival in the overall population of patients with stage IB to IIIA disease, 89% of those in the osimertinib group and 52% of those in the placebo group were alive and disease-free at 24 months (overall hazard ratio for disease recurrence or death, 0.20; 99.12% CI, 0.14 to 0.30; P<0.001), equating to an 80% reduction in the risk of disease recurrence or death with osimertinib. Patients who received osimertinib had fewer locoregional and distant relapses and fewer CNS recurrence events than those who received placebo (1% vs. 10%). Overall survival results were immature at the time of this interim analysis.
Q: Did the ADAURA trial raise any new safety concerns associated with the use of osimertinib?
A: A low frequency of dose modifications and discontinuations of osimertinib and no new safety concerns were reported. All interstitial lung disease (grouped terms) events were mild or moderate in severity and were generally considered to be less clinically severe than those previously observed in patients with advanced disease, and all patients recovered. Furthermore, no notable differences between the trial groups were observed with respect to cardiac adverse events.
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