Lu Shun, Wu Lin, Wang Qiming, Wang Ziping, Lv Dongqing, Ma Rui, Zhu Bo, van Tran Ngoc, Jiang Liyan, Nan Kejun, Laktionov Konstantin, Clarke Stephen, Song Minghao, Mann Helen, Liu Yinglei, Shi Xiaojin, Wu Yi-Long
Shanghai Lung Cancer Centre, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
The Department of Thoracic Medical Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China.
J Thorac Oncol. 2025 Mar;20(3):366-382. doi: 10.1016/j.jtho.2024.10.024. Epub 2024 Nov 7.
PEARL (NCT03003962) is an open-label, phase 3 study comparing first-line durvalumab monotherapy with chemotherapy in patients with metastatic NSCLC (mNSCLC [EGFR/ALK wild type]) with programmed cell death ligand 1 (PD-L1) tumor cell (TC) membrane expression status of 25% or higher. We report the final analysis of PEARL.
Adults (N = 669) with previously untreated stage IV mNSCLC were randomized (1:1) to durvalumab 20 mg/kg every four weeks or chemotherapy every three weeks for four to six cycles. The dual primary endpoints were overall survival (OS) in the population with PD-L1 TC of 25% or higher and OS in the population at low risk of early mortality (LREM) with PD-L1 TC of 25% or higher.
Durvalumab was associated with a numerical reduction in the risk of death versus chemotherapy in the 25% and higher PD-L1 TC population (OS hazard ratio [HR] = 0.84, 95% confidence interval [CI]: 0.71-0.99, p = 0.037; median OS 14.6 months, 95% CI: 12.2-16.9 versus 12.8 months, 95% CI: 10.1-14.7, respectively). In the 25% and higher PD-L1 TC low risk of early mortality population the OS hazard ratio for durvalumab versus chemotherapy was 0.96 (95% CI: 0.79-1.15, p = 0.628); median OS 14.6 months (95% CI: 12.6-17.2) versus 15.0 months (95% CI: 13.1-16.8), respectively. In the safety population, the incidence of grade 3 or 4 treatment-related adverse events was 15.5% (durvalumab) and 45.9% (chemotherapy).
Durvalumab did not statistically significantly improve OS versus chemotherapy as first-line treatment in patients with mNSCLC and 25% and higher PD-L1 TC. The numerical improvement in OS was consistent with previous studies of first-line immune checkpoint inhibitor monotherapy in patients with mNSCLC.
PEARL（NCT03003962）是一项开放标签的3期研究，比较一线度伐利尤单抗单药治疗与化疗在转移性非小细胞肺癌（mNSCLC[表皮生长因子受体/间变性淋巴瘤激酶野生型]）患者中的疗效，这些患者的程序性细胞死亡配体1（PD-L1）肿瘤细胞（TC）膜表达状态为25%或更高。我们报告PEARL的最终分析结果。
将669例既往未接受过治疗的IV期mNSCLC成年患者随机（1:1）分为两组，一组每四周接受一次20mg/kg度伐利尤单抗治疗，另一组每三周接受一次化疗，共进行4至6个周期。两个主要终点分别是PD-L1 TC为25%或更高的人群的总生存期（OS），以及PD-L1 TC为25%或更高且早期死亡风险较低（LREM）人群的OS。
在PD-L1 TC为25%及以上的人群中，与化疗相比，度伐利尤单抗使死亡风险有一定程度的降低（OS风险比[HR]=0.84，95%置信区间[CI]：0.71-0.99，p=0.037；中位OS分别为14.6个月，95%CI：12.2-16.9与12.8个月，95%CI：10.1-14.7）。在PD-L1 TC为25%及以上且早期死亡风险较低的人群中，度伐利尤单抗与化疗的OS风险比为0.96（95%CI：0.79-1.15，p=0.628）；中位OS分别为14.6个月（95%CI：12.6-17.2）与15.0个月（95%CI：13.1-16.8）。在安全性人群中，3级或4级治疗相关不良事件的发生率分别为15.5%（度伐利尤单抗）和45.9%（化疗）。
对于mNSCLC且PD-L1 TC为25%及以上的患者，度伐利尤单抗作为一线治疗在统计学上并未显著改善OS。OS的数值改善与既往mNSCLC患者一线免疫检查点抑制剂单药治疗的研究结果一致。
