Nivolumab Plus Ipilimumab Versus EXTREME Regimen as First-Line Treatment for Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck: The Final Results of CheckMate 651.
Nivolumab Plus Ipilimumab Versus EXTREME Regimen as First-Line Treatment for Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck: The Final Results of CheckMate 651.
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DOI：
10.1200/jco.22.00332
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发表时间：
2023-04-20
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CheckMate 651 （ClinicalTrials.gov标识号：NCT02741570）评估了一线nivolumab + ipilimumab与EXTREME（西妥昔单抗+顺铂/卡铂+氟尿嘧啶≤6个周期，然后西妥昔单抗维持）治疗复发/转移性头颈部鳞状细胞癌（R/M SCCHN）的疗效。未接受过R/M SCCHN全身治疗的患者按1:1随机分配到纳武单抗+伊匹单抗或EXTREME组。主要终点为所有随机分配和程序性死亡-配体1联合阳性评分(CPS)≥20个人群的总生存期（OS）。次要终点包括程序性死亡配体1 CPS≥1人群的OS，以及所有随机分配和CPS≥20人群的无进展生存期、客观缓解率和缓解持续时间。在随机分配的947例患者中，38.3%的患者CPS≥20。在所有随机分配的人群（中位数：13.9 v 13.5个月；风险比[HR]， 0.95; 97.9% CI， 0.80至1.13;P = .4951）和CPS≥20（中位数：17.6 v 14.6个月；HR, 0.78; 97.51% CI， 0.59至1.03;P = .0469）中，纳武单抗联合伊匹单抗与EXTREME的OS无统计学差异。在CPS≥1的患者中，中位OS为15.7个月vs 13.2个月（HR, 0.82; 95% CI, 0.69 ~ 0.97）。在CPS≥20的患者中，中位无进展生存期为5.4个月（纳武单抗+伊匹单抗）vs 7.0个月（EXTREME），客观缓解率为34.1% vs 36.0%，中位缓解持续时间为32.6 vs 7.0个月。3/4级治疗相关不良事件发生在纳武单抗联合伊匹单抗治疗的患者中为28.2%，而极端治疗组为70.7%。在所有随机分配或CPS≥20的人群中，CheckMate 651未达到其主要OS终点。与EXTREME相比，Nivolumab联合ipilimumab显示出更好的安全性。R/M SCCHN患者仍然需要新的治疗方法。
CheckMate 651 (ClinicalTrials.gov identifier: NCT02741570) evaluated first-line nivolumab plus ipilimumab versus EXTREME (cetuximab plus cisplatin/carboplatin plus fluorouracil ≤ six cycles, then cetuximab maintenance) in recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Patients without prior systemic therapy for R/M SCCHN were randomly assigned 1:1 to nivolumab plus ipilimumab or EXTREME. Primary end points were overall survival (OS) in the all randomly assigned and programmed death-ligand 1 combined positive score (CPS) ≥ 20 populations. Secondary end points included OS in the programmed death-ligand 1 CPS ≥ 1 population, and progression-free survival, objective response rate, and duration of response in the all randomly assigned and CPS ≥ 20 populations. Among 947 patients randomly assigned, 38.3% had CPS ≥ 20. There were no statistically significant differences in OS with nivolumab plus ipilimumab versus EXTREME in the all randomly assigned (median: 13.9 v 13.5 months; hazard ratio [HR], 0.95; 97.9% CI, 0.80 to 1.13; P = .4951) and CPS ≥ 20 (median: 17.6 v 14.6 months; HR, 0.78; 97.51% CI, 0.59 to 1.03; P = .0469) populations. In patients with CPS ≥ 1, the median OS was 15.7 versus 13.2 months (HR, 0.82; 95% CI, 0.69 to 0.97). Among patients with CPS ≥ 20, the median progression-free survival was 5.4 months (nivolumab plus ipilimumab) versus 7.0 months (EXTREME), objective response rate was 34.1% versus 36.0%, and median duration of response was 32.6 versus 7.0 months. Grade 3/4 treatment-related adverse events occurred in 28.2% of patients treated with nivolumab plus ipilimumab versus 70.7% treated with EXTREME. CheckMate 651 did not meet its primary end points of OS in the all randomly assigned or CPS ≥ 20 populations. Nivolumab plus ipilimumab showed a favorable safety profile compared with EXTREME. There continues to be a need for new therapies in patients with R/M SCCHN.