真实世界使用奥希替尼治疗非小细胞肺癌: ASTRIS 研究韩国亚组分析。
- 作者列表："Cho BC","Kim DW","Park K","Lee JS","Yoo SS","Kang JH","Lee SY","Kim CH","Jang SH","Kim YC","Yoon HK","Han JY","Kim SW
:Objective: ASTRIS is a large real-world, open-label, multinational clinical study of osimertinib in patients with epidermal growth factor receptor (EGFR) T790M mutation-positive advanced non-small cell lung cancer (NSCLC) who have previously received a tyrosine kinase inhibitor (TKI). We report data from the Korean ASTRIS subgroup.Methods: Adult patients with locally advanced or metastatic NSCLC with a confirmed T790M mutation, WHO performance status of 0-2 and prior EGFR-TKI therapy, received osimertinib 80 mg once daily. Efficacy outcomes were overall survival (OS), investigator-assessed response rate (RR) and progression-free survival (PFS), and time to treatment discontinuation (TTD).Results: At data cut-off (20 October 2017), 466 Korean patients were enrolled. Baseline EGFR molecular testing was mainly performed on biopsied tissue (75.1%). Baseline mutations co-occurring with T790M included exon 19 deletions (60.7%) and L858R (32.8%). 1-year OS was 82.7% (OS data not matured at data cut-off). Overall, RR was 71.0%, median PFS was 12.4 months and median TTD was 15.0 months. In patients with/without CNS metastases, RR was 68.0% and 79.6%, respectively; median PFS, 10.8 and 11.0 months, respectively; and median TTD, 11.2 and 14.7 months, respectively. Overall, 31.1% of patients experienced ≥1 adverse event (AE), leading to dose modification (12.0%), discontinuation (5.2%) or death (2.8%). Serious AEs (24.9%) included pulmonary embolism (1.7%), pleural effusion (1.7%), and pneumonia (1.5%).Conclusion: In this real-world subgroup analysis of Korean patients in the ASTRIS study, osimertinib demonstrated comparable clinical efficacy to that attained in the global ASTRIS study and other clinical trials, with no new safety concerns.
: 目的: ASTRIS 是一项大型真实世界、开放标签、多国临床研究 osimertinib 在表皮生长因子受体 (EGFR) 患者中的应用 t790M 突变阳性的既往接受过酪氨酸激酶抑制剂 (TKI) 的晚期非小细胞肺癌 (NSCLC)。我们报告的数据来自韩国 ASTRIS 亚组。方法: 确诊为 T790M 突变的局部晚期或转移性 NSCLC 成人患者，WHO 表现状态为 0-2，既往接受 EGFR-TKI 治疗，接受 osimertinib 80 mg，每日 1 次。疗效结局为总生存期 (OS) 、研究者评估的缓解率 (RR) 和无进展生存期 (PFS) 以及至停药时间 (TTD)。结果: 在数据截止 (2017年10月20日)，466 名韩国患者入组。主要对活检组织进行基线 EGFR 分子检测 (75.1%)。与 T790M 共同发生的基线突变包括外显子 19 缺失 (60.7%) 和 L858R (32.8%)。1 年 OS 为 82.7% (数据截止时 OS 数据未成熟)。总体而言，RR 为 71.0%，中位 PFS 为 12.4 个月，中位 TTD 为 15.0 个月。在有/无 CNS 转移的患者中，RR 分别为 68.0% 和 79.6%; 中位 PFS 分别为 10.8 和 11.0 个月; 中位 TTD 分别为 11.2 和 14.7 个月。总体而言，31.1% 的患者出现 ≥ 1 次不良事件 (AE)，导致剂量调整 (12.0%) 、停药 (5.2%) 或死亡 (2.8%)。严重 ae (24.9%) 包括肺栓塞 (1.7%) 、胸腔积液 (1.7%) 和肺炎 (1.5%)。结论: 在 ASTRIS 研究中对韩国患者的真实世界亚组分析中，osimertinib 表现出与全球 ASTRIS 研究和其他临床试验中获得的临床疗效相当的临床疗效, 没有新的安全问题。
METHODS:BACKGROUND:The objectives of this study are to assess the chest drainage volumes of patients undergoing anatomic resection of non-small cell lung carcinoma and to determine the safety and effectiveness of administering enoxaparin for thromboprophylaxis. METHODS:A total of 77 patients were included in the study. A study was conducted on the first group of 42 patients in which enoxaparin prophylaxis (enoxaparin, 40 mg) was subcutaneously injected once a day for a period of three days after the patients underwent anatomic pulmonary resection between March 2016 and March 2018. An enoxaparin-free group was identified and included 35 patients who received no enoxaparin prophylaxis after undergoing anatomic pulmonary resection between February 2013 and February 2016. We compared the changes in hemoglobin (Hb) levels, postoperative 3-day drainage volume, transfusion volume, pulmonary complications and length of stay between the two groups. RESULTS:No differences in postoperative Hb levels, chest drainage volume, transfusion volume, postoperative complications, and length of stay were observed between the two groups. Deep-vein thrombosis was noted in a patient in the enoxaparin-free group. No major bleeding was noted in either group. CONCLUSION:We found that for patients undergoing anatomic resection of primary lung cancer, the blood transfusion and chest drainage volumes did not differ, regardless of whether the patients were given enoxaparin. To the best of our knowledge, the impact of low-molecular-weight heparin on chest tube drainage volume for patients undergoing anatomic resection of non-small cell lung carcinoma has not been investigated before.
METHODS::The aim of the present study was to compare the safety and efficacy of cryoablation (CA) and microwave ablation (MWA) as treatments for non-small cell lung cancer (NSCLC). Patients with stage IIIB or IV NSCLC treated with CA (n=45) or MWA (n=56) were enrolled in the present study. The primary endpoint was progression-free survival (PFS); the secondary endpoints included overall survival (OS) time and adverse events (AEs). The median PFS times between the two groups were not significantly different (P=0.36): CA, 10 months [95% confidence interval (CI), 7.5-12.4] vs. MWA, 11 months (95% CI, 9.5-12.4). The OS times between the two groups were also not significantly different (P=0.07): CA, 27.5 months (95% CI, 22.8-31.2 months) vs. MWA, 18 months (95% CI, 12.5-23.5). For larger tumors (>3 cm), patients treated with MWA had significantly longer median PFS (P=0.04; MWA, 10.5 months vs. CA, 7.0 months) and OS times (P=0.04; MWA, 24.5 months vs. CA, 14.5 months) compared patients treated with CA. However, for smaller tumors (≤3 cm), median PFS (P=0.79; MWA, 11.0 months vs. CA, 13.0 months) and OS times (P=0.39; MWA, 30.0 months vs. CA, 26.5 months) between the two groups did not differ significantly. The incidence rates of AEs were similar in the two groups (P>0.05). The number of applicators, tumor size and length of the lung traversed by applicators were associated with a higher risk of pneumothorax and intra-pulmonary hemorrhage in the two groups. Treatment with CA resulted in significantly less intraprocedural pain compared with treatment with MWA (P=0.001). Overall, the present study demonstrated that CA and MWA were comparably safe and effective procedures for the treatment of small tumors. However, treatment with MWA was superior compared with CA for the treatment of large tumors.
METHODS:BACKGROUND:BRAF mutations occurring in 1%-5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSé vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort. PATIENTS AND METHODS:Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS). RESULTS:Of the 118 patients enrolled, 101 presented with a BRAFV600 mutation and 17 with BRAFnonV600 mutations; the median follow-up was 23.9 months. In the BRAFnonV600 cohort, no objective response was observed and this cohort was stopped. In the BRAFV600 cohort, 43/96 patients had objective responses. The mean Bayesian estimated success rate was 44.9% [95% confidence intervals (CI) 35.2%-54.8%]. The ORR had a 99.9% probability of being ≥30%. Median response duration was 6.4 months, median PFS was 5.2 months (95% CI 3.8-6.8), and OS was 10 months (95% CI 6.8-15.7). The vemurafenib safety profile was consistent with previous publications. CONCLUSION:Routine biomarker screening of NSCLC should include BRAFV600 mutations. Vemurafenib monotherapy is effective for treating patients with BRAFV600-mutated NSCLC but not those with BRAFnonV600 mutations. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT02304809.