ADAURA: Adjuvant osimertinib improves DFS in EGFR-positive NSCLC

Osimertinib as adjuvant therapy following complete resection of early-stage EGFR-positive non-small-cell lung cancer (NSCLC) has demonstrated superior disease-free survival (DFS) benefit vs placebo that led to early unblinding of the ADAURA study, according to results reported at the American Society of Clinical Oncology 2020 (ASCO20) Virtual Scientific Programme.

“The results 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, ASCO20 Virtual, abstract LBA5]

“Given the impressive and substantial DFS improvements with adjuvant osimertinib demonstrated in ADAURA, the third-generation EGFR-tyrosine kinase inhibitor [TKI] should be considered the new standard of care after complete resection of early-stage EGFR-positive NSCLC,” said discussant Dr David Spigel of Sarah Cannon Research Institute, Nashville, Tennessee, US.  

In the phase III, randomized, double-blind ADAURA study, 682 patients with completely resected stage IB/II/IIIA EGFR-positive NSCLC were randomized to receive osimertinib 80 mg once daily (n=339) or placebo (n=343), with or without adjuvant chemotherapy, for a planned duration of 3 years. The maximum interval between surgery and randomization was 10 weeks for patients not treated with adjuvant chemotherapy, and 26 weeks for those treated with adjuvant chemotherapy

“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 DFS in patients with stage II/IIIA disease was significantly improved with osimertinib vs placebo (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). “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,” reported Herbst.

The secondary endpoint of DFS in the overall population (ie, patients with stage IB/II/IIIA disease) was also significantly improved 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 with osimertinib were observed in all subgroups analyzed, including in patients treated or not treated with 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.

In the study, the safety profile of osimertinib was consistent with previous reports. The most commonly reported adverse events (AEs) in the osimertinib arm included diarrhoea (all grades, 46 percent vs 19 percent for placebo), paronychia (25 percent vs 1 percent) and dry skin (23 percent vs 6 percent). 

Grade ≥3 AEs occurred in 20 percent of patients receiving osimertinib vs 14 percent of those 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 of those in the placebo arm.

“ADAURA is a well-designed study that demonstrated the substantial DFS benefits across subsets of patients and the well tolerated safety profile of osimertinib after complete resection of early-stage EGFR-positive NSCLC,” commented Spigel. “However, due to early unblinding of the study, it remains uncertain whether treatment with osimertinib eliminates or simply delays the growth of residual disease.”