Osimertinib Shows No OS Benefit Versus Chemotherapy in EGFR T790M-Mutant Advanced NSCLC Study

A statistically significant overall survival benefit was not observed with osimertinib compared with platinum-pemetrexed therapy as treatment of patients with EGFR T790M-mutated advanced non–small cell lung cancer.

A statistically significant benefit was not observed in terms of overall survival (OS) with the EGFR tyrosine kinase inhibitor (TKI) osimertinib (Tagrisso) compared with platinum-pemetrexed therapy as treatment of patients with EGFR T790M-mutated advanced non–small cell lung cancer (NSCLC), according to the final OS data from the AURA3 clinical trial (NCT02151981).1

The hazard ratio (HR) for median OS was 0.87, but the analysis had an HR of 0.54 when OS was adjusted for crossover. Additionally, 73% of patients who had been treated with platinum-pemetrexed chemotherapy received subsequent treatment with osimertinib.

“In patients with [EGFR] T790M advanced NSCLC, no statistically significant benefit in OS was observed for osimertinib versus platinum-pemetrexed, which possibly reflects the high crossover rate of patients from platinum-pemetrexed to osimertinib,” wrote the study authors.2

Osimertinib also significantly improved progression-free survival (PFS), as well as the responses, in patients with EGFR T790M-mutated advanced NSCLC who progressed on a prior EGFR TKI.1

The median OS with osimertinib was 26.8 months (95% CI, 23.5-31.5) versus 22.5 months (95% CI, 20.2-28.8) with the chemotherapy (95% CI, 0.67-1.12; P =.277). The estimated 24-month survival rates were 55% with osimertinib versus 43% with chemotherapy, and the estimated 36-month survival rates were 37% versus 30%, respectively.

The time to first subsequent therapy or death demonstrated a clinically meaningful advantage favoring osimertinib (HR, 0.21; 95% CI, 0.16-0.28; P =.001). At the data cut-off date, 99 patients (73%) in the chemotherapy arm had crossed over to osimertinib, and 66 (67%) had died. Platinum chemotherapy was the most common subsequent anticancer treatment (65%) to follow osimertinib.

The most common adverse event (AEs) that were possibly related to the study treatment included diarrhea in 32% and rash in 32% for the osimertinib arm compared with nausea in 47% in the platinum-pemetrexed arm. Grade 3 or higher diarrhea and rash occurred in 1% each in the osimertinib arm versus grade 3 or higher nausea in the platinum-pemetrexed arm (3%). Grade 3 or higher treatment-related AEs were observed less frequently in this study for osimertinib (9%) versus platinum-pemetrexed treatment (34%).

Patients were randomized 2:1 to receive either oral osimertinib (n = 136) at 80 mg once daily or pemetrexed with carboplatin/cisplatin intravenously every 3 weeks for up to 6 cycles (n = 140). The patients were allowed to cross over to the osimertinib treatment upon progression, confirmed by a blinded independent central review. The primary end point of the study was PFS, while OS and safety were secondary end points.

At the data cut-off date of March 15, 2019, a total of 188 patients (67%) who received osimertinib and 93 (66%) who received the chemotherapy had died.


1. No OS benefit in EGFR T790M advanced NSCLC treated with osimertinib vs chemotherapy. News Release. ESMO. September 2, 2020. Accessed September 3, 2020. https://bit.ly/2ENYsrw

2. Papadimitrakopoulou VA, Mok TS, Han J-Y, et al. Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis. Annals of Oncology. Published online 27 August 2020. doi: https://doi.org/10.1016/j.annonc.2020.08.2100