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

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.

_Reference

_{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}