A randomised non-comparative phase II study of atezolizumab, bevacizumab and chemotherapy in EGFR-mutant NSCLC with acquired resistance – The ETOP 15-19 ABC-lung trial

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer Pub Date : 2025-02-20 DOI:10.1016/j.lungcan.2025.108454

R.A. Soo , K. Vervita , M. Früh , B.C. Cho , M. Majem , D. Rodriguez Abreu , K. Ribi , A. Callejo , T. Moran , M. Domine Gomez , M. Provencio , A. Addeo , J.Y. Han , A.L. Ortega Granados , M. Reck , A. Blasco , R. Garcia Campelo , M.A. Sala González , C. Britschgi , H. Roschitzki-Voser , R.A. Stahel

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引用次数: 0

Abstract

Background

ABC-lung explores the potential effect of combining atezolizumab and bevacizumab with either carboplatin/paclitaxel (ABCPac) or pemetrexed (ABPem) in patients with EGFR-mutant NSCLC, resistant to tyrosine kinase inhibitors (TKIs).

Methods

ABC-lung is a 1:1 randomised, non-comparative, phase II trial, stratified by prior treatment with a third-generation EGFR TKI, evaluating atezolizumab (1200 mg, Q3W) and bevacizumab (15mg/kg, Q3W) with either 4-6 cycles of carboplatin (AUC5, Q3W) and paclitaxel (175-200 mg/m2, Q3W) or pemetrexed (500 mg/m2, Q3W) until progression (PD). The study aimed to improve the 1-year progression-free survival (PFS) rate from 18% to 37%, assessed per RECISTv1.1, separately in each arm. To reject the null hypothesis, at least 14 of 45 evaluable patients in each arm needed to be progression-free at 1-year (power 83%, 1-sided a=0.023). Secondary endpoints included overall survival (OS), objective response rate (ORR), PFS, quality of life (QoL) and adverse events (AEs).

Results

Between 09/2020 and 09/2022, 95 patients were randomized (ABCPac:45; ABPem:50) with median follow-up time of 19 months. From the evaluable patients, 9 in ABCPac and 11 in ABPem arms reached 1-year without progression, lower than the success criterion of 14 patients. Median PFS was 6.4 months in ABCPac and 7.6 months in the ABPem arms, while median OS was 15.4 months and 15.6 months, respectively. Grade ≥3 treatment-related AEs were experienced by 50% and 42% of patients in ABCPac and ABPem arms, respectively, while no grade 5 AEs were recorded.

Conclusions

The observed 1-year PFS rate with atezolizumab, bevacizumab in combination with either carboplatin-paclitaxel or pemetrexed was below the aspired rate of 37% in both arms. The safety is consistent with the known toxicity profiles.

Clinical trial identification: NCT04245085.

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atezolizumab， bevacizumab和化疗治疗egfr突变NSCLC获得性耐药的随机非比较II期研究- ETOP 15-19 ABC-lung试验

背景：abc -lung研究探讨了atezolizumab和bevacizumab联合卡铂/紫杉醇（ABCPac）或培美曲塞（ABPem）治疗对酪氨酸激酶抑制剂（TKIs）耐药的egfr突变型NSCLC患者的潜在影响。sbc -lung是一项1:1随机、非比较的II期试验，通过先前使用第三代EGFR TKI进行分层，评估阿特唑单抗（1200mg, Q3W）和贝伐单抗（15mg/kg, Q3W）与卡铂（AUC5, Q3W）和紫杉醇（175- 200mg /m2, Q3W）或培美曲塞（500mg /m2, Q3W）的4-6个周期直至进展（PD）。该研究旨在将每组1年无进展生存率（PFS）从18%提高到37%，分别根据RECISTv1.1进行评估。为了拒绝原假设，每组45例可评估患者中至少有14例需要在1年内无进展（功率83%，单侧a=0.023）。次要终点包括总生存期（OS）、客观缓解率（ORR）、PFS、生活质量（QoL）和不良事件（ae）。结果在2020年9月至2022年9月期间，95例患者被随机分配(ABCPac:45；ABPem:50)，中位随访时间19个月。在可评估的患者中，9例ABCPac组和11例ABPem组达到1年无进展，低于14例患者的成功标准。ABCPac组和ABPem组的中位PFS分别为6.4个月和7.6个月，而中位OS分别为15.4个月和15.6个月。ABCPac组和ABPem组分别有50%和42%的患者出现≥3级治疗相关不良事件，而没有记录到5级不良事件。结论阿特唑单抗、贝伐单抗联合卡铂-紫杉醇或培美曲塞的1年PFS率均低于预期的37%。其安全性与已知的毒性特征一致。临床试验鉴定：NCT04245085。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Lung Cancer 医学-呼吸系统

CiteScore

9.40

自引率

3.80%

发文量

407

审稿时长

25 days

期刊介绍： Lung Cancer is an international publication covering the clinical, translational and basic science of malignancies of the lung and chest region.Original research articles, early reports, review articles, editorials and correspondence covering the prevention, epidemiology and etiology, basic biology, pathology, clinical assessment, surgery, chemotherapy, radiotherapy, combined treatment modalities, other treatment modalities and outcomes of lung cancer are welcome.