Neoadjuvant ipilimumab and nivolumab in resectable cutaneous squamous cell carcinoma: a randomized phase 2 trial.

CSCC has been demonstrated to be highly responsive to neoadjuvant anti-PD-1 immune-checkpoint blockade (ICB).

已证实CSCC对新辅助抗PD-1免疫检查点阻断（ICB）具有高度反应性。

However, efficacy and safety of neoadjuvant anti-PD-1 combined with anti-CTLA-4 are lacking.

然而，新辅助抗PD-1联合抗CTLA-4的疗效和安全性尚不明确。

In the MATISSE trial, the primary objective was met to investigate the pathological response rate on neoadjuvant nivolumab (NIVO) and nivolumab plus ipilimumab (NIVO + IPI) at the time of standard of care (SOC: surgery ± RT), defined as the proportion of remaining viable tumor cells in the surgical specimen.

在MATISSE试验中，主要研究目标是调查在标准治疗（SOC：手术±放疗）时新辅助纳武利尤单抗（NIVO）和纳武利尤单抗联合伊匹木单抗（NIVO + IPI）的病理反应率，定义为手术标本中剩余的活肿瘤细胞比例。

Fifty patients with stage I-IVa resectable CSCC were treated with NIVO (weeks 0 and 2) or NIVO (weeks 0 and 2) plus low-dose IPI (week 0) before SOC in week 4.

50名I-IVa期可切除性CSCC患者接受了NIVO（第0周和第2周）或NIVO（第0周和第2周）联合低剂量IPI（第0周）治疗，然后在第4周接受SOC。

The median follow-up was 31 months.

中位随访时间为31个月。

Forty patients underwent SOC; 9 of 20 (45%) patients who received NIVO and 10 of 20 (50%) patients who received NIVO + IPI reached a major pathological response (MPR) and 2 of 20 (10%) patients with NIVO and 6 of 20 (30%) with NIVO + IPI reached a partial pathological response (PPR), resulting in pathological response rates of 55% and 80%, respectively.

40名患者接受了SOC治疗；在20名接受NIVO治疗的患者中，有9名（45%）达到了主要病理缓解（MPR），而在20名接受NIVO + IPI治疗的患者中，有10名（50%）达到了MPR。在20名接受NIVO治疗的患者中，有2名（10%）达到了部分病理缓解（PPR），而在20名接受NIVO + IPI治疗的患者中，有6名（30%）达到了PPR，从而分别达到了55%和80%的病理缓解率。

MPR or PPR was accompanied by 2-year disease-specific survival (DSS) of 100%.

主要病理缓解（MPR）或部分病理缓解（PPR）伴随着100%的2年疾病特异性生存率（DSS）。

ICB was safe with 12% (NIVO) and 8% (NIVO + IPI), grade 3, immune-related toxicity without surgical delays.

ICB治疗是安全的，NIVO组和NIVO + IPI组分别有12%和8%的患者出现了3级免疫相关性毒性，但没有导致手术延迟。

Ten patients opted to decline surgery and RT, of whom nine reached durable organ preservation and a clinical complete remission on two ICB infusions alone, accompanied by a 2-year DSS of 100% and favorable health-related quality of life.

有十名患者选择拒绝手术和放疗，其中九人在仅接受两次ICB输注后实现了器官的持久保存和临床完全缓解，伴随的是2年疾病特异性生存期（DSS）为100%，并且健康相关的生活质量良好。

Early changes in [18F]fluorodeoxyglucose positron emission tomography/computed tomography's total lesion glycolysis can safely select patients for response-guided treatment de-escalation in future trials.

早期的[18F]氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描的总病灶糖酵解变化可以安全地为未来试验中的反应指导治疗降级选择患者。

The ClinicalTrials.gov identifier is: NCT04620200 .

ClinicalTrials.gov的标识符是：NCT04620200。