Long-Term Efficacy and Safety of Entrectinib in ROS1 Fusion-Positive NSCLC.
Long-Term Efficacy and Safety of Entrectinib in ROS1 Fusion-Positive NSCLC.
复制标题
DOI：
10.1016/j.jtocrr.2022.100332
复制
发表时间：
2022-06
影响因子：
--
通讯作者：
Siena, Salvatore
中科院分区：
文献类型：
--
作者：
Drilon, Alexander;Chiu, Chao-Hua;Fan, Yun;Cho, Byoung Chul;Lu, Shun;Ahn, Myung-Ju;Krebs, Matthew G.;Liu, Stephen, V;John, Thomas;Otterson, Gregory A.;Tan, Daniel S. W.;Patil, Tejas;Dziadziuszko, Rafal;Massarelli, Erminia;Seto, Takashi;Doebele, Robert C.;Pitcher, Bethany;Kurtsikidze, Nino;Heinzmann, Sebastian;Siena, Salvatore
恩曲替尼是一种被批准用于ROS1融合阳性非小细胞肺癌的酪氨酸激酶抑制剂(TKI)。对ALKA-372-001、STARTRK-1和STARTRK-2试验中的恩曲替尼进行了最新的综合分析，具有相当长的随访期、更多的患者，并首次描述了中位总生存期(OS)。对ROS1融合阳性的非小细胞肺癌伴中枢神经系统(CNS)进展的患者进行了一项探索性分析。ROS1融合阳性、局部晚期或转移性NSCLC的成年患者接受了至少一剂恩替替尼治疗，并有12个月或更长时间的随访期。通过盲法独立中心评价确定共同主要终点的客观有效率(ORR)和有效持续时间(DOR)。数据截止日期为2020年8月31日。可评估疗效的人群包括168名ROS1 TKI-幼稚患者。中位生存期29.1个月(四分位数范围21.8~35.9)。ORR为68%(95%可信区间：60.2~74.8)，中位生存期为20.5个月。中位无进展生存(PFS)为15.7个月，中位OS为47.8个月。在25例基线可测的中枢神经系统转移患者中，颅内ORR为80%(95%CI：59.3~93.2)，中位DOR为12.9个月，中位PFS为8.8个月。在18例仅有中枢神经系统疾病进展的患者中，2例部分缓解(11%)，4例病情稳定(22%)。在该队列中的7例可测量的中枢神经系统疾病患者中，颅内ORR为14%(1例部分缓解)。恩替替尼是有效的，可以延长ROS1 TKI-NAYVE患者ROS1融合阳性非小细胞肺癌的生存时间。在克里佐替尼后仅有中枢神经系统进展的患者中可以看到适度的活动。
Entrectinib is an approved tyrosine kinase inhibitor (TKI) for ROS1 fusion–positive NSCLC. An updated integrated analysis of entrectinib from the ALKA-372-001, STARTRK-1, and STARTRK-2 trials is presented, with substantially longer follow-up, more patients, and the first description of the median overall survival (OS). An exploratory analysis of entrectinib in ROS1 fusion–positive NSCLC with the central nervous system (CNS)–only progression post-crizotinib is reported. Adults with ROS1 fusion–positive, locally advanced or metastatic NSCLC who received at least one dose of entrectinib and had 12 months or longer of follow-up were included in the analysis. Co-primary end points were confirmed objective response rate (ORR) and duration of response (DoR) by blinded independent central review. The data cutoff was on August 31, 2020. The efficacy-assessable population comprised 168 ROS1 TKI–naïve patients. The median survival follow-up was 29.1 months (interquartile range, 21.8–35.9). The ORR was 68% (95% confidence interval [CI]: 60.2–74.8); the median DoR was 20.5 months. The median progression-free survival (PFS) was 15.7 months and the median OS was 47.8 months. In the 25 patients with measurable baseline CNS metastases, the intracranial ORR was 80% (95% CI: 59.3–93.2), median intracranial DoR was 12.9 months, and median intracranial PFS was 8.8 months. Among 18 patients with CNS-only progression on previous crizotinib treatment, two achieved a partial response (11%) and four had stable disease (22%). In seven patients with measurable CNS disease from this cohort, the intracranial ORR was 14% (1 partial response). Entrectinib is active and achieves prolonged survival in ROS1 TKI–naïve patients with ROS1 fusion–positive NSCLC. Modest activity is seen in patients with CNS-only progression post-crizotinib.
登录
查看更多内容
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
7.3
作者：
Menichincheri, Maria;Ardini, Elena;Orsini, Paolo
通讯作者：
Orsini, Paolo
DOI：
10.1016/j.annonc.2020.05.006
发表时间：
2020-09
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Liu D;Flory J;Lin A;Offin M;Falcon CJ;Murciano-Goroff YR;Rosen E;Guo R;Basu E;Li BT;Harding JJ;Iyer G;Jhaveri K;Gounder MM;Shukla NN;Roberts SS;Glade-Bender J;Kaplanis L;Schram A;Hyman DM;Drilon A
通讯作者：
Drilon A
DOI：
10.1016/j.jtho.2018.07.001
发表时间：
2018-11
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Patil T;Smith DE;Bunn PA;Aisner DL;Le AT;Hancock M;Purcell WT;Bowles DW;Camidge DR;Doebele RC
通讯作者：
Doebele RC
DOI：
10.1038/s41571-020-0408-9
发表时间：
2021-01
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Drilon A;Jenkins C;Iyer S;Schoenfeld A;Keddy C;Davare MA
通讯作者：
Davare MA