抗 PD-1/PD-L1 治疗复发性和/或转移性头颈部鳞状细胞癌患者中的超进展。
Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.
机构信息
Department of Medical Oncology, Centre Antoine Lacassagne, Nice.
Department of Medical Oncology, Institut Curie, Paris & Saint-Cloud.
出版信息
Ann Oncol. 2017 Jul 1;28(7):1605-1611. doi: 10.1093/annonc/mdx178.
BACKGROUND
Pembrolizumab and nivolumab are immune checkpoint inhibitors targeting PD-1 that have recently been approved in pretreated recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. In the clinic, some patients seem not only not to benefit from anti-PD-L1/PD-1 agents but rather to experience an acceleration of tumor growth kinetics (TGK).
PATIENTS AND METHODS
We retrospectively compared TGK on immunotherapy and TGK on last treatment in patients with R/M HNSCC treated with PD-1/PD-L1 inhibitors in four French centers. The TGK ratio (TGKR, ratio of the slope of tumor growth before treatment and the slope of tumor growth on treatment) was calculated. Hyperprogression was defined as a TGKR ≥ 2.
RESULTS
From September 2012 to September 2015, 34 patients were identified. Patterns of recurrence included exclusive loco-regional recurrence in 14 patients, exclusive distant metastases in 11 patients, and both in 9 patients. No pseudo-progression was observed. Hyperprogression was observed in 10 patients (29%), including 9 patients with at least a locoregional recurrence, and only 1 patient with exclusively distant metastases. Hyperprogression significantly correlated with a regional recurrence (TGKR ≥ 2: 90% versus TGKR < 2: 37%, P = 0.008), but not with local or distant recurrence. Hyperprogression was associated with a shorter progression-free survival (PFS) according to RECIST (P = 0.003) and irRECIST (P = 0.02), but not with overall survival (P = 0.77).
CONCLUSIONS
Hyperprogression was observed in 29% of patients with R/M HNSCC treated with anti-PD-L1/PD-1 agents and correlated with a shorter PFS. It occurred in 39% of patients with at least a locoregional recurrence and 9% of patients with exclusively distant metastases. No pseudo-progressions were reported. Mechanisms and causality of hyperprogression should further be assessed through prospective controlled studies.
背景
帕博利珠单抗和纳武利尤单抗是针对 PD-1 的免疫检查点抑制剂，最近已被批准用于治疗预处理后的复发性和/或转移性头颈部鳞状细胞癌（R/M HNSCC）患者。在临床中，一些患者似乎不仅没有从抗 PD-L1/PD-1 药物中获益，反而经历了肿瘤生长动力学（TGK）的加速。
患者和方法
我们回顾性比较了在法国的四个中心接受 PD-1/PD-L1 抑制剂治疗的 R/M HNSCC 患者在免疫治疗和最后一次治疗中的 TGK。计算了 TGK 比值（TGKR，治疗前肿瘤生长斜率与治疗期间肿瘤生长斜率之比）。高进展被定义为 TGKR≥2。
结果
从 2012 年 9 月至 2015 年 9 月，共确定了 34 例患者。复发模式包括 14 例患者仅局部区域复发、11 例患者仅远处转移、9 例患者同时存在局部区域和远处转移。未观察到假性进展。10 例患者（29%）观察到高进展，其中 9 例患者至少有局部区域复发，仅有 1 例患者仅远处转移。高进展与区域复发显著相关（TGKR≥2：90%；TGKR<2：37%，P=0.008），但与局部或远处复发无关。根据 RECIST（P=0.003）和 irRECIST（P=0.02）标准，高进展与较短的无进展生存期（PFS）相关，但与总生存期（OS）无关（P=0.77）。
结论
在接受抗 PD-L1/PD-1 药物治疗的 R/M HNSCC 患者中，有 29%观察到高进展，且与较短的 PFS 相关。在至少有局部区域复发的患者中，有 39%观察到高进展，在仅有远处转移的患者中，有 9%观察到高进展。未报告假性进展。应通过前瞻性对照研究进一步评估高进展的机制和因果关系。
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