奥希替尼+培美曲塞及贝伐单抗三联化疗对EGFR突变型NSCLC的疗效分析

目的:探讨奥希替尼、培美曲塞、贝伐单抗三联化疗对表皮生长因子受体（EGFR）突变型非小细胞肺癌（NSCLC）的疗效及安全性。方法:对2016年7月至2018年12月威海市中心医院收治并确诊的106例EGFR突变型NSCLC患者临床资料进行回顾性分析,根据资料中患者的治疗方法不同纳入对照组和观察组,各53例。对照组男31...     

Three-Year Safety,Tolerability, and Health-Related Quality of Life Outcomes of Adjuvant Osimertinib in Patients With Resected Stage IB to IIIA EGFR-Mutated NSCLC: Updated Analysis From the Phase 3 ADAURA Trial

IntroductionIn ADAURA, adjuvant osimertinib significantly improved disease-free survival versus placebo in resected stage IB to IIIA EGFR-mutated NSCLC. We report in-depth analyses of three-year safety, tolerability, and health-related quality of life (HRQoL) from ADAURA.MethodsPatients were randomized 1:1 to osimertinib 80 mg or placebo once daily for up to 3 years. Safety assessments were performed at baseline, week 2, week 4, week 12, and every 12 weeks until treatment completion or discontinuation, and 28 days after treatment was stopped. The SF-36 survey measured HRQoL at baseline, week 12, week 24, and every 24 weeks until recurrence, treatment completion or discontinuation. Data cutoff: April 11, 2022.ResultsSafety and HRQoL analysis sets: osimertinib, n = 337 and n = 339; placebo, n = 343 each. Median (range) total exposure duration was longer with osimertinib versus placebo: 35.8 (0–38) versus 25.1 (0–39) months. Most adverse events (AEs) were first reported within 12 months of starting treatment (osimertinib 97%, placebo 86%). AEs leading to dose reduction, interruption or discontinuation were reported in 12%, 27% and 13% respectively of patients with osimertinib; 1%, 13% and 3% with placebo. Stomatitis and diarrhea were the most common AEs leading to osimertinib dose reduction or interruption; interstitial lung disease was the most common leading to osimertinib discontinuation (per protocol). There were no differences in time to deterioration for SF-36 physical, mental component summaries between osimertinib and placebo.ConclusionsNo new safety signals were reported and HRQoL was maintained with 3 years of adjuvant osimertinib treatment. Combined with significant efficacy benefit, these data further support adjuvant osimertinib in stage IB to IIIA EGFR-mutated NSCLC.     

Recent Advances on the Role of EGFR Tyrosine Kinase Inhibitors in the Management of NSCLC With Uncommon,Non Exon 20 Insertions,EGFR Mutations

The first-line treatment of choice for patients with EGFR mutation-positive NSCLC is an EGFR tyrosine kinase inhibitor (TKI), of which five as follows are predominantly available in practice: gefitinib, erlotinib, afatinib, dacomitinib, and osimertinib. Most prospective clinical trial data with these agents are limited to patients with the common activating and sensitizing EGFR mutations as follows: exon 19 deletions and exon 21 L858R point mutations. However, 10% to 20% of patients with NSCLC harbor uncommon EGFR mutations that have variable sensitivity to different EGFR TKIs. Owing to their molecular structures, afatinib, dacomitinib, and osimertinib have broader inhibitory profiles than the first-generation agents, gefitinib and erlotinib. Nevertheless, the paucity of prospective clinical data, the wide heterogeneity of uncommon mutations, and the existence of compound mutations in up to 25% of the cases complicate treatment decisions in this patient subgroup. Here, we collate the latest preclinical and clinical data regarding the activity of different TKIs against major uncommon EGFR mutations including compound mutations, but excluding exon 20 insertions which are generally insensitive to TKIs. On the basis of these data, we offer suggestions regarding treatment strategies for uncommon EGFR mutations. Moving forward, it will be important to include uncommon EGFR mutations in the first-line molecular analysis of all patients with adenocarcinoma of the lung, as this will help optimize patient outcomes according to their precise genotype.     

Randomized Phase 2 Study of Osimertinib Plus Bevacizumab Versus Osimertinib for Untreated Patients With Nonsquamous NSCLC Harboring EGFR Mutations: WJOG9717L Study

IntroductionTo evaluate the efficacy and safety of osimertinib plus bevacizumab for previously untreated patients with advanced nonsquamous NSCLC harboring EGFR-sensitizing mutations.MethodsWe conducted a randomized, open-label, phase 2 study at 21 institutions in Japan. Previously untreated patients with advanced nonsquamous NSCLC harboring EGFR-sensitizing mutations received either osimertinib (80 mg, daily) plus bevacizumab (15 mg/kg, every 3 wk) or osimertinib monotherapy, and were stratified according to sex, stage, and EGFR mutation status. The primary end point was progression-free survival (PFS) in the intention-to-treat population, assessed by means of blinded, independent central radiologic review.ResultsBetween January 2018 and September 2018, a total of 122 patients were enrolled (osimertinib + bevacizumab arm, 61 patients; osimertinib monotherapy arm, 61 patients). At a median follow-up duration of 19.8 months, the median PFS was 22.1 months for osimertinib plus bevacizumab and 20.2 months for osimertinib monotherapy, with a hazard ratio of 0.862 (60% confidence interval: 0.700–1.060, 95% confidence interval: 0.531–1.397, one-sided stratified log-rank p = 0.213). Adverse events of grade 3 or worse were observed in 34 patients (56%) in the osimertinib plus bevacizumab arm and 29 (48%) in the osimertinib monotherapy arm. In addition, two (3%) and 11 patients (18%) experienced any grade pneumonitis, respectively, and grade 3 pneumonitis was observed in one patient (2%) in each arm.ConclusionsThis study failed to exhibit the efficacy of osimertinib plus bevacizumab for improving the PFS among patients with nonsquamous NSCLC harboring EGFR mutations as first-line treatment.     

奥希替尼联合培美曲塞加卡铂治疗晚期非鳞状非小细胞肺癌的疗效

探讨奥希替尼联合培美曲塞+卡铂单用与联用治疗晚期非鳞状非小细胞肺癌患者临床疗效及对免疫功能的影响。方法 选取2016年12月～2020年12月我院收治的晚期非鳞状非小细胞肺癌患者168例,根据随机数字表法将患者分为A组（奥希替尼组）、B组（培美曲塞+卡铂组） 及联合组（奥希替尼联合培美曲塞+卡铂组）,每组56例。A组给予奥希替尼治疗,B组给予培美曲塞+卡铂治疗,联合组则给予奥希替尼联合培美曲塞+卡铂治疗,对3组治疗疗效进行比较分析。结果 联合组疾病控制率均高于A组与B组（P＜0.05）;免疫功能相关指标与治疗前相比,3组治疗后CD3 +、CD4 +、CD4 +/CD8 +水平均明显提高（P＜0.05）,CD8 +水平降低（P＜0.05）,其中联合组上述各指标改善程度较A、B两组更优,差异有统计学意义（P＜0.05）;联合组不良反应总发生率与A组、B组比较差异无统计学意义（P＞0.05）。结论 晚期非鳞状非小细胞肺癌患者给予奥希替尼联合培美曲塞+卡铂治疗临床效果较好,能够改善患者免疫功能,疗效安全可靠,可在临床推广应用。