帕博利珠单抗联合或不联合化疗治疗复发性或转移性头颈部鳞状细胞癌：III 期 KEYNOTE-048 研究的更新结果。

Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study.

机构信息

The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, National Institute of Health Research Biomedical Research Centre, London, United Kingdom.

Yale Cancer Center and Yale School of Medicine, New Haven, CT.

出版信息

J Clin Oncol. 2023 Feb 1;41(4):790-802. doi: 10.1200/JCO.21.02508. Epub 2022 Oct 11.

PURPOSE

Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048. Post hoc analysis of long-term efficacy and progression-free survival on next-line therapy (PFS2) is presented.

METHODS

Patients were randomly assigned (1:1:1) to pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy. Efficacy was evaluated in programmed death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, CPS ≥ 1, and total populations, with no multiplicity or alpha adjustment.

RESULTS

The median study follow-up was 45.0 months (interquartile range, 41.0-49.2; n = 882). At data cutoff (February 18, 2020), overall survival improved with pembrolizumab in the PD-L1 CPS ≥ 20 (hazard ratio [HR], 0.61; 95% CI, 0.46 to 0.81) and CPS ≥ 1 populations (HR, 0.74; 95% CI, 0.61 to 0.89) and was noninferior in the total population (HR, 0.81; 95% CI, 0.68 to 0.97). Overall survival improved with pembrolizumab-chemotherapy in the PD-L1 CPS ≥ 20 (HR, 0.62; 95% CI, 0.46 to 0.84), CPS ≥ 1 (HR, 0.64; 95% CI, 0.53 to 0.78), and total (HR, 0.71; 95% CI, 0.59 to 0.85) populations. The objective response rate on second-course pembrolizumab was 27.3% (3 of 11). PFS2 improved with pembrolizumab in the PD-L1 CPS ≥ 20 (HR, 0.64; 95% CI, 0.48 to 0.84) and CPS ≥ 1 (HR, 0.79; 95% CI, 0.66 to 0.95) populations and with pembrolizumab-chemotherapy in the PD-L1 CPS ≥ 20 (HR, 0.64; 95% CI, 0.48 to 0.86), CPS ≥ 1 (HR, 0.66; 95% CI, 0.55 to 0.81), and total (HR, 0.73; 95% CI, 0.61 to 0.88) populations. PFS2 was similar after pembrolizumab and longer after pembrolizumab-chemotherapy on next-line taxanes and shorter after pembrolizumab and similar after pembrolizumab-chemotherapy on next-line nontaxanes.

CONCLUSION

With a 4-year follow-up, first-line pembrolizumab and pembrolizumab-chemotherapy continued to demonstrate survival benefit versus cetuximab-chemotherapy in recurrent/metastatic head and neck squamous cell carcinoma. Patients responded well to subsequent treatment after pembrolizumab-based therapy.

目的

帕博利珠单抗和帕博利珠单抗联合化疗在 KEYNOTE-048 研究中显示出对复发性/转移性头颈部鳞状细胞癌的疗效。本文报告了后续二线治疗（PFS2）的长期疗效和无进展生存的事后分析。

方法

患者以 1:1:1 的比例随机分配至帕博利珠单抗、帕博利珠单抗联合化疗或西妥昔单抗联合化疗组。在程序性死亡配体 1（PD-L1）联合阳性评分（CPS）≥20、CPS≥1 和总人群中评估疗效，未进行多重性或 α 调整。

结果

中位研究随访时间为 45.0 个月（四分位距，41.0-49.2；n=882）。在数据截止日期（2020 年 2 月 18 日）时，在 PD-L1 CPS≥20（风险比[HR]，0.61；95%置信区间，0.46 至 0.81）和 CPS≥1 人群中，与安慰剂相比，帕博利珠单抗改善了总生存期（HR，0.74；95%置信区间，0.61 至 0.89），在总人群中，与安慰剂相比，帕博利珠单抗非劣效性（HR，0.81；95%置信区间，0.68 至 0.97）。在 PD-L1 CPS≥20（HR，0.62；95%置信区间，0.46 至 0.84）、CPS≥1（HR，0.64；95%置信区间，0.53 至 0.78）和总人群（HR，0.71；95%置信区间，0.59 至 0.85）中，与安慰剂相比，帕博利珠单抗联合化疗改善了总生存期。在二线帕博利珠单抗治疗中，客观缓解率为 27.3%（11 例中有 3 例）。在 PD-L1 CPS≥20（HR，0.64；95%置信区间，0.48 至 0.84）和 CPS≥1（HR，0.79；95%置信区间，0.66 至 0.95）人群中，与安慰剂相比，帕博利珠单抗改善了 PFS2，在 PD-L1 CPS≥20（HR，0.64；95%置信区间，0.48 至 0.86）、CPS≥1（HR，0.66；95%置信区间，0.55 至 0.81）和总人群（HR，0.73；95%置信区间，0.61 至 0.88）中，帕博利珠单抗联合化疗改善了 PFS2。在二线紫杉醇类药物中，与帕博利珠单抗相比，后续治疗的 PFS2 相似，而在二线非紫杉醇类药物中，与帕博利珠单抗相比，PFS2 更短。