Department of Thoracic Head and Neck Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, USA.
State Key Laboratory of Translational Oncology, Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong, People's Republic of China.
Ann Oncol. 2020 Nov;31(11):1536-1544. doi: 10.1016/j.annonc.2020.08.2100. Epub 2020 Aug 27.
In AURA3 (NCT02151981), osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), significantly prolonged progression-free survival and improved response in patients with EGFR T790M advanced non-small-cell lung cancer (NSCLC) and progression on prior EGFR-TKI treatment. We report the final AURA3 overall survival (OS) analysis.
Adult patients were randomized 2 : 1 to osimertinib (80 mg orally, once daily) or pemetrexed plus carboplatin/cisplatin (platinum-pemetrexed) intravenously, every 3 weeks (≤6 cycles). Patients could crossover to osimertinib on progression confirmed by blinded independent central review. OS and safety were secondary end points.
A total of 279 patients were randomly assigned to receive osimertinib and 140 to platinum-pemetrexed (136 received treatment). At data cut-off (DCO; 15 March 2019), 188 patients (67%) receiving osimertinib versus 93 (66%) receiving platinum-pemetrexed had died. The hazard ratio (HR) for OS was 0.87 [95% confidence interval (CI) 0.67-1.12; P = 0.277]; the median OS was 26.8 months (95% CI 23.5-31.5) versus 22.5 months (95% CI 20.2-28.8) for osimertinib and platinum-pemetrexed, respectively. The estimated 24- and 36-month survival was 55% versus 43% and 37% versus 30%, respectively. After crossover adjustment, there was an HR of 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 < 0.001). At DCO, 99/136 (73%) patients in the platinum-pemetrexed arm had crossed over to osimertinib, 66/99 (67%) of whom had died. 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, versus nausea (47%; grade ≥3, 3%) in the platinum-pemetrexed arm.
In patients with 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.
ClinicalTrials.gov NCT02151981; https://clinicaltrials.gov/ct2/show/NCT02151981.
在 AURA3 研究（NCT02151981）中，第三代表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKI）奥希替尼显著延长了先前接受 EGFR-TKI 治疗后进展的伴有 EGFR T790M 突变的晚期非小细胞肺癌（NSCLC）患者的无进展生存期并改善了缓解率。我们报告了最终的 AURA3 总生存期（OS）分析结果。
成年患者以 2:1 的比例随机分配接受奥希替尼（80mg 口服，每日 1 次）或培美曲塞联合卡铂/顺铂（顺铂-培美曲塞）静脉滴注，每 3 周（≤6 个周期）。患者在经过盲法独立中心审查确认疾病进展后可以交叉使用奥希替尼。OS 和安全性是次要终点。
共 279 例患者随机分配接受奥希替尼治疗，140 例患者接受顺铂-培美曲塞治疗（136 例患者接受治疗）。截至数据截止日期（DCO；2019 年 3 月 15 日），188 例（67%）接受奥希替尼治疗的患者和 93 例（66%）接受顺铂-培美曲塞治疗的患者死亡。OS 的风险比（HR）为 0.87（95%CI 0.67-1.12；P=0.277）；奥希替尼组和顺铂-培美曲塞组的中位 OS 分别为 26.8 个月（95%CI 23.5-31.5）和 22.5 个月（95%CI 20.2-28.8）。估计 24 个月和 36 个月的生存率分别为 55%和 43%，37%和 30%。交叉调整后，HR 为 0.54（95%CI 0.18-1.6）。首次后续治疗或死亡的时间显示奥希替尼具有临床意义的优势（HR 0.21，95%CI 0.16-0.28；P<0.001）。在 DCO 时，顺铂-培美曲塞组的 136 例患者中有 99 例（73%）交叉至奥希替尼组，其中 66 例（67%）死亡。最常见的可能与研究治疗相关的不良事件是腹泻（32%；≥3 级，1%）和皮疹（分组术语；32%；≥3 级，<1%），奥希替尼组中，而顺铂-培美曲塞组中恶心（47%；≥3 级，3%）更为常见。
在伴有 T790M 突变的晚期 NSCLC 患者中，奥希替尼与顺铂-培美曲塞相比，OS 无统计学显著获益，这可能反映了从顺铂-培美曲塞交叉至奥希替尼的患者比例较高。
ClinicalTrials.gov NCT02151981；https://clinicaltrials.gov/ct2/show/NCT02151981。
