柳叶刀:默沙东的帕姆单抗治疗初治进展期NSCLC的生活质量优于化疗
帕姆单抗(Pembrolizumab)由默沙东公司开发,2014年在美国首次上市,是第一只在美国上市的PD-1抑制剂。近期,顶级医学期刊《柳叶刀》杂志发布了帕姆单抗对非小细胞肺癌患者健康相关生活质量研究的结果。

研究背景在KEYNOTE-024的三期临床试验中,相比铂类药物,帕姆单抗在治疗初治进展性、且PD-L1阳性(PD-L1阳性比例大于或等于50%)非小细胞肺癌具有更常的无进展生存期。这里,我们报导帕姆单抗与化疗相比,以患者报告结局(patient-reported outcomes, PROs)作为研究终点的差异。


研究结果在2014年9月19日至2015年10月29日之间,305名患者被随机分配到帕姆单抗组(n=154)及化疗组(n=151)。每组有3名患者在所有时间点未完成任何PRO,因此共有299名患者被纳入到最后的研究数据集中。在这些患者中,每组有1名患者在15周前未完成PRO,因此我们未纳入前15周的结果。在研究初始PRO依从性高于90%,两组15周时约80%。从基线到15周,最小二乘方均值变化QLQ-C30 GHS/QOL指数帕姆单抗为6.9(95%置信区间3.3-10.6),化疗组为-0.9(-4.8-3.0),相差7.8(2.9-12.8,双侧P=0.0020)。帕姆单抗治疗的患者QLQ-LC13综合结局恶化的患者更少(151名患者中46名[31%]vs  148 名患者中58名[39%])。帕姆单抗组发生恶化的时间比化疗更长(未及中位数[95%置信区间8.5- ] vs 5.0月 [3.6- ]; 风险比0.66, 95% 置信区间0.44-0.97;双侧p=0.029)。


研究解读与化疗相比,帕姆单抗提高或维持了健康相关的生活质量,或许可以作为表达PD-L1的进展期非小细胞肺癌新的标准一线用药。


Background

In the phase 3 KEYNOTE-024 trial, treatment with pembrolizumab conferred longer progression-free survival than did platinum-based therapy in patients with treatment-naive, advanced non-small-cell lung cancer (NSCLC) with a programmed cell death-ligand 1 (PD-L1) tumour proportion score of 50% or greater (PD-L1-positive). Here we report the prespecified exploratory endpoint of pembrolizumab versus chemotherapy on patient-reported outcomes (PROs).


Findings

Between Sept 19, 2014, and Oct 29, 2015, 305 patients were randomly assigned to pembrolizumab (n=154) or chemotherapy (n=151). Three patients in each group did not complete any PRO instruments at any timepoints, and so 299 patients were included in the full analysis set. Of these patients, one in each group did not complete any PRO instruments before week 15, and so were not included in analyses of change from baseline to week 15. PRO compliance was greater than 90% at baseline and approximately 80% at week 15 for both groups. Least-squares mean baseline-to-week-15 change in QLQ-C30 GHS/QOL score was 6·9 (95% CI 3·3 to 10·6) for pembrolizumab and −0·9 (−4·8 to 3·0) for chemotherapy, for a difference of 7·8 (2·9 to 12·8; two-sided nominal p=0·0020). Fewer pembrolizumab-treated patients had deterioration in the QLQ-LC13 composite endpoint than did chemotherapy-treated patients (46 [31%] of 151 patients vs 58 [39%] of 148 patients). Time to deterioration was longer with pembrolizumab than with chemotherapy (median not reached [95% CI 8·5 to not reached] vs 5·0 months [3·6 to not reached]; hazard ratio 0·66, 95% CI 0·44–0·97; two-sided nominal p=0·029).


Interpretation

Pembrolizumab improves or maintains health-related QOL compared with that for chemotherapy, and might represent a new first-line standard of care for PD-L1-expressing, advanced NSCLC.


Reference: Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial


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