In patients with epidermal growth factor receptor (EGFR) T790M advanced non–small cell lung cancer (NSCLC), no statistically significant benefit in overall survival was observed with osimertinib vs pemetrexed plus carboplatin/cisplatin (platinum/pemetrexed) treatment, which possibly reflects the high crossover rate of patients from platinum/pemetrexed to osimertinib. The final results from the AURA3 study were reported by Vassiliki Papadimitrakopoulou, MD, and colleagues in Annals of Oncology.
The hazard ratio (HR) for median overall survival was 0.87, while analysis of overall survival adjusted for crossover showed an HR of 0.54. A high percentage (73%) of patients treated with platinum/pemetrexed chemotherapy were subsequently treated with osimertinib in this study.
Vassiliki Papadimitrakopoulou, MD
Osimertinib is a third-generation, irreversible, oral EGFR tyrosine kinase inhibitor that potently and selectively inhibits both EGFR tyrosine kinase inhibitor–sensitizing and T790M resistance mutations and has demonstrated efficacy in patients with NSCLC, including those with central nervous system metastases.
AURA3
The authors wrote in the study background that in the AURA3 trial, osimertinib significantly prolonged progression-free survival and improved response in patients with EGFR T790M advanced NSCLC who disease had progressed following prior EGFR tyrosine kinase inhibitor treatment. In their article in Annals of Oncology, the investigators reported the final overall survival analysis of this study.
In AURA3, adult patients were randomly assigned 2:1 to receive oral osimertinib at 80 mg once daily or pemetrexed plus carboplatin/cisplatin given intravenously every 3 weeks for up to 6 cycles. Patients could cross over to the osimertinib arm after disease progression confirmed by blinded independent central review. The secondary endpoints were overall survival and safety.
In total, 279 patients were randomly assigned to receive osimertinib; 140 patients were randomly assigned to receive platinum/pemetrexed, of whom 136 received the doublet. At data cut-off in March 2019, 188 patients (67%) receiving osimertinib and 93 patients (66%) receiving platinum/pemetrexed had died.
Overall Survival Analysis
The HR for overall survival was 0.87 (95% confidence interval [CI] = 0.67–1.12, P = .277), with a median overall survival of 26.8 months (95% CI = 23.5–31.5) vs 22.5 months (95% CI = 20.2–28.8), respectively. The estimated 24- and 36-month survival rates were 55% vs 43% and 37% vs 30%, respectively.
After crossover adjustment, the HR was 0.54 (95% CI = 0.18–1.6). Time to first subsequent therapy or death showed a clinically meaningful advantage toward osimertinib (HR = 0.21, 95% CI = 0.16–0.28, P < .001). At data cut-off, 99 of 136 patients (73%) in the platinum/pemetrexed arm had crossed over to osimertinib, and 66 of 99 (67%) had died. Among patients receiving subsequent anticancer therapy, platinum chemotherapy was most common after osimertinib (65%).
The most common adverse events possibly related to study treatment were diarrhea (32%; grade ≥ 3, 1%) and rash (grouped term; 32%; grade ≥ 3, < 1%) in the osimertinib arm vs nausea (47%; grade ≥ 3, 3%) in the platinum/pemetrexed arm. Grade ≥ 3 possibly treatment-related adverse events were observed less frequently with osimertinib (9%) than with platinum/pemetrexed (34%).
The authors concluded that no statistically significant benefit in overall survival was observed for treatment with osimertinib vs platinum/pemetrexed in AURA3, possibly reflecting the high crossover rate of patients from the platinum/pemetrexed arm to receive osimertinib. However, the continued tolerable safety profile reported for osimertinib, together with superior progression-free survival, improved patient quality of life and resulted in a longer time to symptom deterioration vs platinum/pemetrexed, they noted. This reinforces osimertinib as standard-of-care second-line treatment for patients with EGFR T790M advanced NSCLC and disease progression on a prior EGFR tyrosine kinase inhibitor treatment.
Disclosure: The study was funded by AstraZeneca. For full disclosures of the study authors, visit annalsofoncology.org.
