Neoadjuvant nivolumab for patients with resectable HPV-positive and HPV-negative squamous cell carcinomas of the head and neck in the CheckMate 358 trial.
Neoadjuvant nivolumab for patients with resectable HPV-positive and HPV-negative squamous cell carcinomas of the head and neck in the CheckMate 358 trial.
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DOI：
10.1136/jitc-2021-002568
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发表时间：
2021-06
影响因子：
10.9
通讯作者：
Topalian SL
中科院分区：
文献类型：
--
作者：
Ferris RL;Spanos WC;Leidner R;Gonçalves A;Martens UM;Kyi C;Sharfman W;Chung CH;Devriese LA;Gauthier H;Chiosea SI;Vujanovic L;Taube JM;Stein JE;Li J;Li B;Chen T;Barrows A;Topalian SL
头颈部鳞状细胞癌（HNSCCs）是由致癌物引起的常见恶性肿瘤，包括烟草和酒精，或感染人类乳头状瘤病毒（HPV）。针对程序性细胞死亡1 （PD-1）途径的免疫检查点抑制剂对不可切除的复发/转移性HNSCC有效。在这里，我们探讨了抗pd -1治疗在新辅助环境下高危可切除hpv阳性和hpv阴性HNSCC的安全性和有效性。病毒相关癌症的I/II期CheckMate 358试验评估了新辅助nivolumab在先前未治疗的可切除hpv阳性或hpv阴性HNSCC患者中的应用。患者在第1天和第15天静脉注射nivolumab 240mg，计划在第29天进行手术。通过监测不良事件（ae）和手术延迟来评估安全性/耐受性（主要终点）。术前使用RECIST v1.1测量放射学反应，适用于单次纳武单抗后评估。使用基于免疫的标准检查病理标本的治疗反应。2015年11月至2017年12月，52例AJCC（第七版）III-IV期可切除的HNSCC患者接受了新辅助纳武单抗治疗（26例hpv阳性，26例hpv阴性）。在hpv阳性组和hpv阴性组中，分别有19例（73.1%）和14例（53.8%）患者发生了任何级别的治疗相关ae (TRAEs)；3-4级trae分别发生5例（19.2%）和3例（11.5%）。没有患者有方案定义的trae相关手术延迟（bb10 4周）。据报道，38名患者接受了完全的手术切除，10名患者因协议误解而计划在纳沃单抗后进行活检，而不是最终手术，4名患者未接受手术或活检，其中2名患者肿瘤进展。在49例可评估患者中，hpv阳性组和hpv阴性组的放射学应答率分别为12.0%和8.3%。手术患者没有完全的部位或中心检查的病理反应。在17例可集中评价的hpv阳性肿瘤中，1例（5.9%）达到主要病理反应，3例（17.6%）达到部分病理反应（pPR）；在17例可集中评估的hpv阴性肿瘤中，1例（5.9%）达到pPR。新辅助nivolumab在hpv阳性（23.5%）和hpv阴性（5.9%）肿瘤中通常是安全的，并诱导病理消退。联合新辅助治疗方案和高风险肿瘤的术后持续治疗在未来的试验中是必要的，以提高该方法的疗效。ClinicalTrials.gov NCT02488759;https://clinicaltrials.gov/ct2/show/NCT02488759。
Head and neck squamous cell carcinomas (HNSCCs) are common malignancies caused by carcinogens, including tobacco and alcohol, or infection with human papillomavirus (HPV). Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1) pathway are effective against unresectable recurrent/metastatic HNSCC. Here, we explored the safety and efficacy of anti-PD-1 therapy in at-risk resectable HPV-positive and HPV-negative HNSCC in the neoadjuvant setting. The phase I/II CheckMate 358 trial in virus-associated cancers assessed neoadjuvant nivolumab in patients with previously untreated, resectable HPV-positive or HPV-negative HNSCC. Patients received nivolumab 240 mg intravenously on days 1 and 15, with surgery planned by day 29. Safety/tolerability (primary endpoint) was assessed by monitoring adverse events (AEs) and surgical delays. Radiographic response was measured before surgery using RECIST v1.1, adapted for a single post-nivolumab evaluation. Pathologic specimens were examined for treatment response using immune-based criteria. From November 2015 to December 2017, 52 patients with AJCC (seventh edition) stage III–IV resectable HNSCC received neoadjuvant nivolumab (26 HPV-positive, 26 HPV-negative). Any-grade treatment-related AEs (TRAEs) occurred in 19 patients (73.1%) and 14 patients (53.8%) in the HPV-positive and HPV-negative cohorts, respectively; grade 3–4 TRAEs occurred in five (19.2%) and three patients (11.5%), respectively. No patient had a protocol-defined TRAE-related surgical delay (>4 weeks). Thirty-eight patients were reported as undergoing complete surgical resection, 10 had a planned post-nivolumab biopsy instead of definitive surgery due to a protocol misinterpretation, and four did not undergo surgery or biopsy, including two with tumor progression. Radiographic response rates in 49 evaluable patients were 12.0% and 8.3% in the HPV-positive and HPV-negative cohorts, respectively. There were no complete pathologic responses by site or central review in operated patients. Among 17 centrally evaluable HPV-positive tumors, one (5.9%) achieved major pathological response and three (17.6%) achieved partial pathologic response (pPR); among 17 centrally evaluable HPV-negative tumors, one (5.9%) achieved pPR. Neoadjuvant nivolumab was generally safe and induced pathologic regressions in HPV-positive (23.5%) and HPV-negative (5.9%) tumors. Combinatorial neoadjuvant treatment regimens, and continued postoperative therapy for high-risk tumors, are warranted in future trials to enhance the efficacy of this approach. ClinicalTrials.gov NCT02488759; https://clinicaltrials.gov/ct2/show/NCT02488759.
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