Gelsomino Francesco, Lamberti Giuseppe, Tiseo Marcello, Rocco Danilo, Pasello Giulia, Cecere Fabiana Letizia, Chella Antonio, Grilli Giada, Mandruzzato Marcella, Tognetto Michele, Garassino Marina Chiara, Macerelli Marianna, Novello Silvia, Roila Fausto, Colantonio Ida, Grossi Francesco, Fiorentino Michelangelo, Ardizzoni Andrea
Medical Oncology Unit, Policlinico S.Orsola-Malpighi, Via Albertoni 15, Bologna, 40138, Italy.
Medical Oncology Unit, Policlinico S.Orsola-Malpighi, Bologna, Italy.
Ther Adv Med Oncol. 2020 Jul 20;12:1758835920915983. doi: 10.1177/1758835920915983. eCollection 2020.
Although immunotherapy with immune-checkpoint inhibitors (ICIs) has profoundly changed the therapeutic scenario in the treatment of advanced non-small cell lung cancer (NSCLC), trials of ICIs only enrolled NSCLC patients with common histology. Atezolizumab was approved by the United States Food and Drug Administration (US FDA) in October 2016 and by the European Medicines Agency (EMA) in September 2017 for the treatment of patients with metastatic NSCLC whose disease progressed during or following platinum-containing chemotherapy, regardless of PD-L1 expression.
We designed a single-arm, multicenter, two-stage phase II study and plan to enroll 43 patients. The primary objective of the study is to evaluate the antitumor activity of atezolizumab in advanced NSCLC patients with rare histology subtypes. Patients with prior atezolizumab or ICI treatment and with untreated, symptomatic, or progressing brain metastases will be excluded. The primary endpoint is disease control rate. Secondary objectives are toxicity and safety, overall response rate, progression-free survival, overall survival, and time to progression. Diagnosis of NSCLC with rare histology will be confirmed by central pathology revision, and will include: colloid carcinoma, fetal adenocarcinoma, non-endocrine large cell carcinoma, sarcomatoid carcinoma, salivary gland-type tumor, lymphoepithelioma-like carcinoma, and NUT-nuclear protein in testis carcinoma. Archival tumor tissue is required for correlative studies of PD-L1 expression on tumor cells and tumor infiltrating lymphocytes.
Therapeutic options in NSCLC with rare histology subtypes, to be assessed in specifically designed trials, are an unmet need. This trial will help elucidate the role of atezolizumab as a viable option in this setting.
尽管免疫检查点抑制剂（ICI）免疫疗法已深刻改变了晚期非小细胞肺癌（NSCLC）的治疗格局，但ICI试验仅纳入了具有常见组织学类型的NSCLC患者。阿替利珠单抗于2016年10月获得美国食品药品监督管理局（US FDA）批准，并于2017年9月获得欧洲药品管理局（EMA）批准，用于治疗在含铂化疗期间或之后疾病进展的转移性NSCLC患者，无论其PD-L1表达情况如何。
我们设计了一项单臂、多中心、两阶段的II期研究，计划招募43名患者。该研究的主要目的是评估阿替利珠单抗在具有罕见组织学亚型的晚期NSCLC患者中的抗肿瘤活性。既往接受过阿替利珠单抗或ICI治疗以及未治疗、有症状或病情进展的脑转移患者将被排除。主要终点是疾病控制率。次要目标包括毒性和安全性、总缓解率、无进展生存期、总生存期和疾病进展时间。具有罕见组织学类型的NSCLC诊断将通过中心病理学复核确认，包括：胶样癌、胎儿腺癌、非内分泌性大细胞癌、肉瘤样癌、涎腺型肿瘤、淋巴上皮瘤样癌和睾丸NUT核蛋白癌。相关研究需要存档肿瘤组织来检测肿瘤细胞和肿瘤浸润淋巴细胞上的PD-L1表达。
在专门设计的试验中评估的具有罕见组织学亚型的NSCLC的治疗选择是一项尚未满足的需求。该试验将有助于阐明阿替利珠单抗在这种情况下作为一种可行选择的作用。
