Pembrolizumab versus chemotherapy in microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer: 5-year follow-up from the randomized phase III KEYNOTE-177 study.

Previous results from KEYNOTE-177 showed a statistically significant and clinically meaningful improvement in progression-free survival(PFS) with pembrolizumab versus chemotherapy ± bevacizumab/cetuximab in MSI-H/dMMR mCRC.

先前的KEYNOTE-177研究结果表明，在MSI-H/dMMR mCRC中，与化疗±贝伐单抗/西妥昔单抗相比，帕博利珠单抗在无进展生存期（PFS）上显示出统计学上显著且具有临床意义的改善。

Results after >5 years of follow-up are reported.

报告了超过5年的随访结果。

patients_and_methods

Adults with untreated MSI-H/dMMR mCRC were randomly assigned 1 : 1 to receive pembrolizumab 200 mg intravenously every 3 weeks or chemotherapy.

未接受治疗的成人MSI-H/dMMR mCRC患者按1:1的比例随机分配，每3周静脉注射200 mg的pembrolizumab或接受化疗。

Patients assigned to chemotherapy could cross over to pembrolizumab after centrally confirmed progressive disease.

被分配接受化疗的患者在中央确认疾病进展后可以转为接受帕博利珠单抗治疗。

Dual primary endpoints were PFS per RECIST v1.1 and overall survival(OS).

双重主要终点是根据RECIST v1.1评估的无进展生存期（PFS）和总生存期（OS）。

Secondary endpoints included duration of response and safety.

次要终点包括反应持续时间和安全性。

Results

At data cut-off (17 July 2023), median follow-up was 73.3 months (range, 64.9-89.2 months).

在数据截止日期（2023年7月17日），中位随访时间为73.3个月（范围，64.9-89.2个月）。

Overall, 307 patients were assigned to receive pembrolizumab (n = 153) or chemotherapy (n = 154).

总体而言，307名患者被分配接受帕博利珠单抗(n = 153)或化疗(n = 154)。

Fifty-seven (37.0%) patients assigned to chemotherapy crossed over to pembrolizumab per protocol; 39 (25.3%) received a programmed cell death protein 1/programmed death-ligand 1 [PD-(L)1] inhibitor off protocol (effective crossover rate, 62%).

根据方案，分配到化疗的57名患者(37.0%)转而接受了帕博利珠单抗；另外39名患者(25.3%)在方案外接受了程序性细胞死亡蛋白1/程序性死亡配体1 [PD-(L)1] 抑制剂治疗（有效交叉率，62%）。

Median OS was 77.5 months with pembrolizumab versus 36.7 months with chemotherapy (hazard ratio, 0.73; 95% confidence interval0.53-0.99); 5-year OS rates were 54.8% versus 44.2%.

中位总生存期（OS）在使用派姆单抗治疗的患者中为77.5个月，而在化疗组为36.7个月（风险比，0.73；95%置信区间0.53-0.99）；5年总生存率分别为54.8%和44.2%。

Median PFS was 16.5 months with pembrolizumab and 8.2 months with chemotherapy (hazard ratio, 0.60; 95% confidence interval0.45-0.79).

中位无进展生存期（PFS）在使用派姆单抗治疗的患者中为16.5个月，而在化疗组为8.2个月（风险比，0.60；95%置信区间0.45-0.79）。

Median duration of response was 75.4 months (range, 2.3+ to 80.1+ months) with pembrolizumab versus 10.6 months (range, 2.8 to 71.5+ months) with chemotherapy.

使用帕博利珠单抗的反应持续时间中位数为75.4个月（范围，2.3+至80.1+个月），而化疗组为10.6个月（范围，2.8至71.5+个月）。

Compared with chemotherapy, fewer patients in the pembrolizumab arm experienced adverse events (80% versus 99%; grade 3-5, 22% versus 67%).

与化疗相比，接受帕博利珠单抗治疗的患者中较少出现不良事件（80%对比99%；3-5级不良事件，22%对比67%）。

Conclusions

With >5 years of follow-up, responses to pembrolizumab remained durable.

随访超过5年，接受派姆单抗治疗的患者的反应持续存在。

Median OS was more than twice as long in patients treated with pembrolizumab versus chemotherapy in first line despite an effective crossover rate of 62%.

尽管有效交叉率达到了62%，但在一线治疗中，接受派姆单抗治疗的患者的中位总生存期是化疗患者的两倍以上。

Pembrolizumab remains a standard of care for MSI-H/dMMR mCRC.

派姆单抗仍然是MSI-H/dMMR转移性结直肠癌的标准治疗方法。