A randomised phase III study of bevacizumab and carboplatin-pemetrexed chemotherapy with or without atezolizumab as first-line treatment for advanced pleural mesothelioma: results of the ETOP 13-18 BEAT-meso trial.

The addition of bevacizumab to chemotherapy improves overall survival(OS).

将贝伐珠单抗加入化疗可改善总生存（OS）。

While single-agent immunotherapy or chemotherapy-immunotherapy combinations are superior to chemotherapy monotherapy, there is a potential for synergistic triple combination of chemotherapy, bevacizumab, and immunotherapy.

尽管单药免疫治疗或化疗联合免疫治疗方案优于化疗单药治疗，但化疗、贝伐单抗和免疫治疗的协同三联方案具有潜在优势。

patients_and_methods

BEAT-meso is an international, open-label, 1 : 1 randomised, phase III trial, with stratification factors histology and stage aiming to determine the efficacy and safety of adding atezolizumab [1200 mg, 3-week cycle (q3w) until progression] to bevacizumab (15 mg/kg, q3w until progression) and standard chemotherapy (4-6 cycles of carboplatin area under the curve with pemetrexed 500 mg/m2, q3w; ABC versus BC) as first-line treatment for advanced DPM.

BEAT-meso是一项国际、开放标签、1:1随机、III期试验，通过组织学和分期进行分层，旨在确定将阿替利珠单抗（每3周1200毫克，直至疾病进展）加入贝伐单抗（每3周15毫克/公斤，直至疾病进展）和标准化疗（卡铂曲线下面积联合培美曲塞500毫克/平方米，每3周一次；4-6个周期；ABC与BC）作为晚期恶性间皮瘤一线治疗的疗效和安全性。

The primary endpoint is OS in all randomised patients, aiming for a relative benefit of 29% [hazard ratio(HR) 0.708].

主要终点是所有随机患者的总生存期，目标是相对获益29% [风险比（HR）0.708]。

Secondary endpoints include progression-free survival(PFS), adverse events (AEs), and symptom-specific and global quality of life (QoL).

次要终点包括无进展生存期（PFS）、不良事件（AEs）以及症状特异性与全球生活质量（QoL）。

Results

Between 30 April 2019 and 7 March 2022, 400 patients were randomised, 200 per arm.

2019年4月30日至2022年3月7日期间，共有400名患者被随机分配，每组200人。

Sixty-five percent had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 and 78% had epithelioid histology.

65%的患者具有东协作肿瘤组（ECOG）表现状态1，78%的患者具有上皮样组织学特征。

At a median follow-up of 35 months (data cut-off 1 September 2023), the median OS was 20.5 months for ABC versus 18.1 months for BC [HR 0.84, 95% confidence interval(CI) 0.66-1.06, P = 0.14].

在中位随访时间为35个月（数据截止至2023年9月1日）时，ABC的中位总生存期为20.5个月，而BC为18.1个月[风险比（HR）0.84，95%置信区间（CI）0.66-1.06，P = 0.14]。

Median PFS was significantly longer for ABC than for BC (9.2 versus 7.6 months) (HR 0.72, 95% CI 0.59-0.89, P = 0.0021).

ABC的中位无进展生存期显著长于BC（9.2个月对比7.6个月）(风险比（HR）0.72，95%置信区间（CI）0.59-0.89，P = 0.0021)。

Histology showed significant treatment interaction for both PFS and OS, with an OS HR of 0.51 (95% CI 0.32-0.80) for non-epithelioid and 1.01 (95% CI 0.77-1.32) for epithelioid (interaction P = 0.012).

组织学显示治疗对无上皮样和上皮样患者的无进展生存期（PFS）和总生存期（OS）有显著的相互作用，无上皮样的OS风险比（HR）为0.51（95%置信区间0.32-0.80），而上皮样的OS HR为1.01（95%置信区间0.77-1.32），相互作用P值为0.012。

Grade ≥3 treatment-related AEs were reported in 55% of patients in ABC and 47% in BC; QoL was maintained with ABC with no clinically meaningful differences from BC.

在ABC组中有55%的患者报告了3级或更高级别的治疗相关不良事件（AEs），而在BC组中为47%；使用ABC组维持了生活质量（QoL），与BC组相比没有临床上有意义的差异。

Conclusions

The significant benefit in median PFS for ABC found in this study translated into a numerical but not significant increase in median OS.

本研究发现，ABC在中位无进展生存期（PFS）上的显著获益转化为中位总生存期（OS）的数值增加，但未达到统计学显著性。

Thus, the primary endpoint was not met.

因此，主要研究终点未达成。

In the pre-specified analysis by histology, superior OS and PFS were found for ABC in non-epithelioid cases.

在按组织学类型预先指定的分析中，对于非上皮样病例，ABC显示出更优越的总生存和无进展生存。