Department of Thoracic Surgery, Thoraxklinik, University Hospital Heidelberg, Heidelberg, Germany; Translational Lung Research Center (TLRC) Heidelberg, Member of the German Center for Lung Research (DZL), Germany.
Translational Lung Research Center (TLRC) Heidelberg, Member of the German Center for Lung Research (DZL), Germany; Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Lung Cancer. 2021 Mar;153:150-157. doi: 10.1016/j.lungcan.2021.01.018. Epub 2021 Jan 21.
A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
Patients with resectable NSCLC stage II/IIIA were included. Two cycles of pembrolizumab (200 mg intravenously once every 3 weeks) were administered prior to surgery. The primary objectives were to assess the feasibility and safety of neoadjuvant pembrolizumab therapy and to evaluate antitumor activity. We analyzed the clinical parameters as well as pathological and radiological tumor response data.
The NSCLC histology was adenocarcinoma for 13 patients and squamous cell carcinoma for 2 patients. All patients but two underwent 2 cycles of pembrolizumab prior to surgery. Four patients (27 %) presented a major pathologic response. Significant tumor target response in positron emission tomography computed tomography (PET-CT) was detected in all 4 pathologic responders. Nevertheless, the PET findings mismatched the tumor load in some patients. A PD-L1 expression ≥10 % in the pretreatment biopsy was associated with at least major pathologic response. Five patients (33 %) presented grade 2-3 treatment related adverse events (TRAE), the overall postoperative morbidity was 7 % and 30-day mortality was 0 %.
Neoadjuvant pembrolizumab is a feasible therapy in surgical lung cancer patients. It was associated with tolerable toxicity and did not compromise tumor resection.
一项评估新辅助程序性死亡受体 1（PD-1）抑制剂帕博利珠单抗（MK-3475，可瑞达）治疗非小细胞肺癌（NSCLC）的Ⅱ期临床试验（NCT03197467）已经开展。我们报告了在入组 15 例患者后计划进行的首次中期安全性分析的初步临床结果。
纳入可手术的Ⅱ/ⅢA 期 NSCLC 患者。患者术前接受 2 个周期的帕博利珠单抗（200mg，静脉注射，每 3 周 1 次）治疗。主要目的是评估新辅助帕博利珠单抗治疗的可行性和安全性，并评估抗肿瘤活性。我们分析了临床参数以及病理和影像学肿瘤反应数据。
NSCLC 组织学为腺癌 13 例，鳞状细胞癌 2 例。除 2 例患者外，所有患者均在术前接受了 2 个周期的帕博利珠单抗治疗。4 例（27%）患者出现主要病理缓解。在所有 4 例病理缓解者中，均在正电子发射断层扫描计算机断层摄影术（PET-CT）中检测到显著的肿瘤靶标反应。然而，在一些患者中，PET 结果与肿瘤负荷不匹配。在预处理活检中 PD-L1 表达≥10%与至少主要病理缓解相关。5 例（33%）患者出现 2-3 级治疗相关不良事件（TRAE），总术后发病率为 7%，30 天死亡率为 0%。
新辅助帕博利珠单抗在手术治疗的肺癌患者中是可行的治疗方法。其具有可耐受的毒性，且不会影响肿瘤切除。
