Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial.
Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial.
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DOI：
10.1158/1078-0432.ccr-20-1695
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发表时间：
2020-10-01
期刊：
影响因子：
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通讯作者：
Adkins DR
中科院分区：
文献类型：
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作者：
Uppaluri R;Campbell KM;Egloff AM;Zolkind P;Skidmore ZL;Nussenbaum B;Paniello RC;Rich JT;Jackson R;Pipkorn P;Michel LS;Ley J;Oppelt P;Dunn GP;Barnell EK;Spies NC;Lin T;Li T;Mulder DT;Hanna Y;Cirlan I;Pugh TJ;Mudianto T;Riley R;Zhou L;Jo VY;Stachler MD;Hanna GJ;Kass J;Haddad R;Schoenfeld JD;Gjini E;Lako A;Thorstad W;Gay HA;Daly M;Rodig SJ;Hagemann IS;Kallogjeri D;Piccirillo JF;Chernock RD;Griffith M;Griffith OL;Adkins DR
Pembrolizumab改善了复发性或转移性头颈部鳞状细胞癌（HNSCC）患者的生存率。本研究的目的是确定pembrolizumab是否安全，是否会导致病理肿瘤反应（pTR），并降低可切除的人乳头瘤病毒（HPV）无关HNSCC患者的复发率。给予新辅助帕博利珠单抗（200 mg），2-3周后进行手术肿瘤消融。计划术后（化疗）放疗。高风险病理学患者（阳性切缘和/或结节扩展）接受辅助帕博利珠单抗治疗。pTR被量化为具有肿瘤坏死、角质碎片和巨细胞/组织细胞的切除床的比例：pTR-0（<10%）、pTR-1（10-49%）和pTR-2（≥50%）。共同主要终点为所有患者的pTR-2和高风险病理学患者的1年复发率（历史：35%）。评估了基线PD-L1和T细胞浸润与pTR的相关性。评估了肿瘤克隆动力学（ClinicalTrials.gov NCT 02296684）。36例患者入组。新辅助pembrolizumab后，未发生严重（3-4级）不良事件和非预期手术延迟/并发症。pTR-2发生在8例患者（22%）中，pTR-1发生在8例其他患者（22%）中。18例高危患者的1年复发率为16.7%（95%CI：3.6-41.4%）。pTR ≥10%与基线肿瘤PD-L1、免疫浸润和IFN-γ活性相关。匹配的样本显示pTR-0患者中抑制性检查点的上调，并证实了一些患者的克隆丢失。在局部晚期HPV无关HNSCC患者中，pembrolizumab是安全的，在44%的患者中观察到任何病理学缓解，病理学完全缓解率为0%。高危病理患者的1年复发率低于历史复发率。
Pembrolizumab improved survival in recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC) patients. The aims of this study were to determine if pembrolizumab would be safe, result in pathologic tumor response (pTR), and lower the relapse rate in patients with resectable human papillomavirus (HPV)-unrelated HNSCC. Neoadjuvant pembrolizumab (200 mg) was administered and followed 2–3 weeks later by surgical tumor ablation. Post-operative (chemo) radiation was planned. High-risk pathology patients (positive margins and/or extranodal extension) received adjuvant pembrolizumab. pTR was quantified as the proportion of the resection bed with tumor necrosis, keratinous debris, and giant cells/histiocytes: pTR-0 (<10%), pTR-1 (10–49%), and pTR-2 (≥50%). Co-primary endpoints were pTR-2 among all patients and one-year relapse rate in patients with high-risk pathology (historical: 35%). Correlations of baseline PD-L1 and T-cell infiltration with pTR were assessed. Tumor clonal dynamics were evaluated (ClinicalTrials.gov NCT02296684). Thirty-six patients enrolled. After neoadjuvant pembrolizumab, serious (grades 3–4) adverse events and unexpected surgical delays/complications did not occur. pTR-2 occurred in eight patients (22%), and pTR-1 in eight other patients (22%). One-year relapse rate among eighteen patients with high-risk pathology was 16.7% (95%CI: 3.6–41.4%). pTR ≥10% correlated with baseline tumor PD-L1, immune infiltrate, and IFN-γ activity. Matched samples showed upregulation of inhibitory checkpoints in patients with pTR-0, and confirmed clonal loss in some patients. Among patients with locally advanced, HPV-unrelated HNSCC, pembrolizumab was safe, and any pathologic response was observed in 44% of patients with 0% pathologic complete responses. The one-year relapse rate in patients with high-risk-pathology was lower than historical.