美国埃默里大学温希普癌症研究所Suresh S. Ramalingam研究组近日取得一项新成果。他们研究了奥希替尼对未经治疗的EGFR突变的晚期非小细胞肺癌患者总生存期的影响。相关论文2019年11月21日发表在《新英格兰医学杂志》上。

奥希替尼是表皮生长因子受体的第三代不可逆酪氨酸激酶抑制剂（EGFR-TKI），可选择性抑制EGFR-TKI-致敏与EGFR-T790M耐药的突变。此前的一项临床3期试验比较了奥希替尼与其他EGFR-TKIs一线治疗EGFR突变阳性的晚期非小细胞肺癌（NSCLC），结果显示奥希替尼的无进展生存期更长，但尚未报告总生存期。

在这项试验中，研究组招募了556名先前未经治疗的EGFR突变型（外显子19缺失或L858R等位基因突变）晚期NSCLC患者，将其按1：1随机分配，其中279名接受奥希替尼治疗，277名接受其他两种EGFR-TKI（对照组，即吉非替尼或厄洛替尼）治疗。

奥希替尼组的中位总生存期为38.6个月，显著高于对照组（31.8个月）。3年后，奥希替尼组中79名（28%）患者和对照组中26名（9%）患者仍继续接受试验方案，并分别持续20.7个月和11.5个月。奥希替尼组和对照组中3级及以上不良事件的发生率分别为42%和47%。

总之，对于先前未经治疗的晚期NSCLC患者，采用奥希替尼治疗与其他EGFR-TKIs相比，可显著延长总生存期，且未增加安全风险。

附：英文原文

Title: Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC

Author: Suresh S. Ramalingam, M.D.,, Johan Vansteenkiste, M.D., Ph.D.,, David Planchard, M.D., Ph.D.,, Byoung Chul Cho, M.D., Ph.D.,, Jhanelle E. Gray, M.D.,, Yuichiro Ohe, M.D., Ph.D.,, Caicun Zhou, M.D., Ph.D.,, Thanyanan Reungwetwattana, M.D.,, Ying Cheng, M.D.,, Busyamas Chewaskulyong, M.D.,, Riyaz Shah, M.D.,, Manuel Cobo, M.D.,, Ki Hyeong Lee, M.D., Ph.D.,, Parneet Cheema, M.D.,, Marcello Tiseo, M.D., Ph.D.,, Thomas John, M.D., Ph.D.,, Meng-Chih Lin, M.D.,, Fumio Imamura, M.D., Ph.D.,, Takayasu Kurata, M.D., Ph.D.,, Alexander Todd, M.Sc.,, Rachel Hodge, M.Sc.,, Matilde Saggese, M.D.,, Yuri Rukazenkov, M.D., Ph.D.,, and Jean-Charles Soria, M.D., Ph.D.

Issue&Volume: 2019-11-21

Abstract:

Background

Osimertinib is a third-generation, irreversible tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKI–sensitizing and EGFR T790M resistance mutations. A phase 3 trial compared first-line osimertinib with other EGFR-TKIs in patients with EGFR mutation–positive advanced non–small-cell lung cancer (NSCLC). The trial showed longer progression-free survival with osimertinib than with the comparator EGFR-TKIs (hazard ratio for disease progression or death, 0.46). Data from the final analysis of overall survival have not been reported.

Methods

In this trial, we randomly assigned 556 patients with previously untreated advanced NSCLC with an EGFR mutation (exon 19 deletion or L858R allele) in a 1:1 ratio to receive either osimertinib (80 mg once daily) or one of two other EGFR-TKIs (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily, with patients receiving these drugs combined in a single comparator group). Overall survival was a secondary end point.

Results

The median overall survival was 38.6 months (95% confidence interval [CI], 34.5 to 41.8) in the osimertinib group and 31.8 months (95% CI, 26.6 to 36.0) in the comparator group (hazard ratio for death, 0.80; 95.05% CI, 0.64 to 1.00; P=0.046). At 3 years, 79 of 279 patients (28%) in the osimertinib group and 26 of 277 (9%) in the comparator group were continuing to receive a trial regimen; the median exposure was 20.7 months and 11.5 months, respectively. Adverse events of grade 3 or higher were reported in 42% of the patients in the osimertinib group and in 47% of those in the comparator group.

Conclusions

Among patients with previously untreated advanced NSCLC with an EGFR mutation, those who received osimertinib had longer overall survival than those who received a comparator EGFR-TKI. The safety profile for osimertinib was similar to that of the comparator EGFR-TKIs, despite a longer duration of exposure in the osimertinib group.

DOI: 10.1056/NEJMoa1913662

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1913662