ADAURA: Osimertinib triumphs in adjuvant treatment of EGFR-positive NSCLC
Osimertinib may become a new standard of care in the adjuvant treatment of early-stage EGFR-positive non-small-cell lung cancer (NSCLC) following complete resection, as the third-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) demonstrated superior survival benefits leading to early unblinding of the ADAURA study.
“Results of the ADAURA study suggest that osimertinib provides a highly effective, practice-changing adjuvant treatment for patients with stage IB/II/IIIA EGFR-positive NSCLC after complete resection,” said investigator Dr Roy Herbst of the Yale School of Medicine and Yale Cancer Center, New Haven, Connecticut, US. [Herbst R, et al, ASCO 2020, abstract LBA5]
The phase III, randomized, double-blind ADAURA study compared osimertinib 80 mg once daily vs placebo, with or without adjuvant chemotherapy, in 682 patients with completely resected stage IB/II/IIIA NSCLC. Treatment was given for a planned duration of 3 years.
“The study was unblinded early due to superior efficacy with osimertinib,” noted Herbst. “Enrolment had been completed at the time of unblinding. All patients were followed up for at least 1 year.”
“The primary endpoint of investigator-assessed disease-free survival [DFS] in patients with stage II/IIIA disease was longer with osimertinib vs placebo, with a high statistical significance [median, not reached vs 20.4 months; hazard ratio (HR), 0.17; 95 percent confidence interval (CI), 0.12 to 0.23; p<0.0001],” reported Herbst. “An early separation of DFS curves was noted. The DFS rates were 97 percent with osimertinib vs 61 percent with placebo at 1 year, 90 percent vs 44 percent at 2 years, and 80 percent vs 28 percent at 3 years.”
Likewise, DFS in the overall population (ie, patients with stage IB/II/IIIA disease) was significantly longer with osimertinib vs placebo (median, not reached vs 28.1 months; HR, 0.21; 95 percent CI, 0.16 to 0.28; p<0.0001).
“The DFS benefits were observed in all analyzed subgroups, including patients who had or had not received adjuvant chemotherapy,” Herbst pointed out.
At 2 years, DFS rates were 87 percent vs 73 percent (HR, 0.50; 95 percent CI, 0.25 to 0.96) in patients with stage IB disease, 91 percent vs 56 percent (HR, 0.17; 95 percent CI, 0.08 to 0.31) in those with stage II disease, and 88 percent vs 32 percent (HR, 0.12; 95 percent CI, 0.07 to 0.20) in those with stage IIIA disease. The DFS curves of the two arms also separated early when patients with stage II or stage IIIA disease were analyzed separately.
“The safety profile was consistent with the established safety profile of osimertinib,” said Herbst. “The most common adverse events [AEs] in the osimertinib arm included diarrhoea, paronychia and dry skin. Grade ≥3 AEs occurred in 20 percent of patients receiving osimertinib vs 14 percent of patients receiving placebo. Three percent of patients in the osimertinib arm had grade 1/2 interstitial lung disease. QTc prolongation was reported in 7 percent of patients in the osimertinib arm vs 1 percent in the placebo arm.”
“ADAURA is a well-designed study that successfully demonstrated the substantial DFS benefits across subsets and well tolerated safety profile of osimertinib after complete resection of early-stage EGFR-positive NSCLC,” commented discussant Dr David Spigel of Sarah Cannon Research Institute, Nashville, Tennessee, US.
“Given the impressive and substantial DFS improvements with adjuvant osimertinib in ADAURA, it should be considered the new standard of care after complete resection of early-stage EGFR-positive NSCLC,” he continued. “However, due to early unblinding of the study, it remains uncertain whether treatment with osimertinib eliminates or simply delays the growth of residual disease.”