Results from the phase 3 ADAURA trial found extended disease-free survival for patients, irrespective of previous adjuvant chemotherapy received or disease stage.
An exploratory analysis of the pivotal phase 3 ADAURA trial (NCT02511106) found that treatment with adjuvant osimertinib (Tagrisso) led to improved disease-free survival (DFS) for patients with EGFR-mutated non-small cell lung cancer (NSCLC), irrespective of prior adjuvant chemotherapy received or disease stage, according to results presented during the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer (WCLC).1
In the overall patient population, adjuvant osimertinib resulted in an 84% reduction in the risk of disease recurrence or death in patients who had previously received adjuvant chemotherapy (HR, 0.16; 95% CI, 0.10-0.26); the reduction was slightly lower, at 77% (HR, 0.23; 95% CI, 0.13-0.40), in those who had not received chemotherapy. Notably, the DFS benefit achieved with adjuvant osimertinib proved to be comparable across all stages of disease examined.
“The overwhelming DFS benefit in patients in ADAURA already supported the role of [osimertinib] as a pioneering therapy in the adjuvant treatment of EGFR-mutated NSCLC,” principal investigator of the trial Yi-Long Wu, MD, FACS, tenured professor of the Lung Cancer Institute at Guangdong Provincial People’s Hospital and Academy of Medical Sciences, stated in a press release. “The latest analysis shows the magnitude of that benefit is consistent with or without prior adjuvant chemotherapy, and regardless of disease stage, reinforcing the critical role of [osimertinib] in this setting.”
The phase 3 trial enrolled a total of 682 patients with completely resected stage IB, II, IIIA NSCLC who had and had not received adjuvant chemotherapy. To be eligible for enrollment, patients had to be at least 18 years of age (20 years or older if from Japan/Taiwan), have a World Health Organization (WHO) performance status of 0 or 1, have confirmed primary nonsquamous disease and an EGFR exon 19 deletion or exon 21 L858R deletion.2
Participants were stratified based on disease stage (IB vs II vs IIIA), EGFR mutation (exon 19 deletion vs exon 21 L858R), and race (Asian vs non-Asian). In the trial, patients were randomized 1:1 to receive either osimertinib at a once-daily dose of 80 mg (n = 339) or once-daily placebo (n = 343). Patients continued to receive treatment until either disease recurrence, treatment was completed, or discontinuation criterion were met.
The primary objective of the trial was DFS per investigator assessment, while key secondary end points comprised DFS in the overall population; DFS at 2, 3, 4, and 5 years; overall survival, safety, and health-related quality of life (QoL).
The median age of study participants was 63 years; 30% were male and 64% were Asian. Approximately 72% of patients were never smokers and the majority(64%) had a WHO performance status of 0. Fifty-five percent of patients had tumors that harbored an EGFR exon 19 deletion, while 45% had an exon 21 L858R deletion. Sixty percent of patients had previously received adjuvant chemotherapy. Notably, younger patients and those with more advanced disease were more likely to have received prior adjuvant chemotherapy, and treatment with chemotherapy did not vary based on a patient’s performance status.
Early results from the trial presented during the 2020 ASCO Virtual Scientific Program showed that adjuvant osimertinib resulted in a statistically significant improvement in DFS in patients with stage IB/II/IIA EGFR-mutated NSCLC. The median DFS, per investigator assessment, had not been reached with osimertinib versus 19.6 months with placebo (HR, 0.17; 95% CI, 0.12-0.23; P <.0001).3 In the overall population, the median DFS also had not been reached in those who received the EGFR TKI versus 27.5 months with placebo (HR, 0.20; 95% CI, 0.15-0.27; P <.0001). These data resulted in the December 2020 FDA approval of osimertinib as adjuvant therapy in select patients with EGFR-mutated NSCLC.
Updated data presented during the 2020 ESMO Virtual Congress showed that treatment with adjuvant osimertinib also resulted in a clinically meaningful improvement in central nervous system (CNS) DFS compared with placebo (HR, 0.18; 95% CI, 0.10-0.33; P <.0001); this translated to an 82% reduction in the risk of CNS disease recurrence or death.2 The median CNS DFS in the overall population had not yet been reached in the investigative arm compared with 48.2 months in the control arm.
Additionally, CNS disease recurrence was found to be less likely with the EGFR TKI versus placebo, with a conditional probability of less than 1% at 18 months with osimertinib.
Additional results presented during the 2020 WCLC showed that in patients who had previously received adjuvant chemotherapy, the DFS HR was not computable in those with stage IB disease, 0.15 (95% CI, 0.06-0.32) in those with stage II disease, and 0.13 (95% CI, 0.06-0.23) in those with stage IIIA disease. In the subgroup of patients who did not previously receive chemotherapy, the DFS HR was 0.38 (95% CI, 0.15-0.88) in those with stage IB disease, 0.20 (95% CI, 0.07-0.52) in those with stage II disease, and 0.10 (95% CI, 0.02-0.29) in those with stage IIIA disease.
Moreover, data from a separate exploratory post-hoc analysis of patient-reported outcomes in the trial demonstrated that those who received the EGFR TKI maintained their QoL, with no clinically meaningful differences in physical or mental health measures observed between the 2 treatment arms.
Regarding safety, the data proved to be consistent with what had previously been reported with osimertinib. Per investigator assessment, all-grade toxicities that were grade 3 or higher in severity were reported in 20% of the patients who received osimertinib versus 13% of those who were given placebo.