Efficacy of pembrolizumab and vorinostat combination in patients with recurrent and/or metastatic squamous cell carcinomas: a phase 2 basket trial.

IF 23.5 1区 医学 Q1 ONCOLOGY
Edith Borcoman, Bastien Cabarrou, Miguel Francisco, Frédéric Bigot, François Ghiringhelli, Damien Vansteene, François Legrand, Maral Halladjian, Célia Dupain, Olivia Le Saux, Clelia Coutzac, Christian Borel, Raphael Chaltiel, Benoit You, Carlos Gomez-Roca, Sophie Cousin, Elodie Coquan, Aurélien Lambert, Esma Saada-Bouzid, Xavier Durando, Mathilde Saint-Ghislain, Gianmaria Frige, Elena Guerini-Rocco, Maria Manuela Tonini, Ivan Bièche, Zahra Castel-Ajgal, Grégoire Marret, Marie-Paule Sablin, Emmanuelle Jeannot, Fabrice Andre, Thomas Filleron, Marta Jimenez, Luca Mazzarella, Nicolas Servant, Maud Kamal, Christophe Le Tourneau
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引用次数: 0

Abstract

Immune checkpoint inhibitors improve the treatment of many solid tumors and have shown encouraging results in advanced squamous cell carcinoma (SCC), yet only a minority of patients respond to immune checkpoint inhibitor monotherapy. We conducted the PEVOsq trial, an open-label, nonrandomized, multicenter, basket phase 2 trial to evaluate the combination of pembrolizumab and vorinostat in recurrent/metastatic SCC of various origins. The primary endpoint was the objective response rate (ORR) in each tumor cohort during treatment as per the investigators' assessment. Secondary endpoints included safety and antitumor activity evaluation in terms of centrally confirmed ORR, progression-free survival, overall survival and duration of response. In the efficacy population (n = 107), the ORR was met in cervical (39%), anal (31%) and vulvar/vaginal (19%) cancer cohorts, but not in head and neck SCC (19%) or penile (18%) cancer cohorts (overall ORR = 26%). Median progression-free survival was 4.0 months (95% confidence interval: 2.6-4.3), and median overall survival was 11.1 months (95% confidence interval: 9.2-17.4). In the safety population, 101 (91%) of 111 patients developed at least one treatment-related adverse event, with 39% and 5.4% of patients experiencing at least one grade 3 and grade 4 treatment-related adverse event, respectively. Vorinostat-related toxicity prompted a dose reduction/interruption in 66% of patients. Whole-exome sequencing analyses revealed several potential predictive biomarkers of response to treatment. Further studies in a larger number of patients are required to validate these findings. ClinicalTrials.gov identifier: NCT04357873 .

派姆单抗和伏立诺他联合治疗复发和/或转移性鳞状细胞癌的疗效:一项2期一揽子试验
免疫检查点抑制剂改善了许多实体肿瘤的治疗,并在晚期鳞状细胞癌(SCC)中显示出令人鼓舞的结果,但只有少数患者对免疫检查点抑制剂单药治疗有反应。我们进行了PEVOsq试验,这是一项开放标签、非随机、多中心、组合式2期试验,旨在评估派姆单抗和伏立诺他联合治疗各种来源的复发/转移性鳞状细胞癌。主要终点是研究人员评估的治疗期间每个肿瘤队列的客观缓解率(ORR)。次要终点包括安全性和抗肿瘤活性评估(以中心确认的ORR、无进展生存期、总生存期和反应持续时间为标准)。在有效人群(n = 107)中,ORR在宫颈(39%)、肛门(31%)和外阴/阴道(19%)癌症队列中达到,但在头颈部鳞状细胞癌(19%)或阴茎(18%)癌症队列中没有达到(总ORR = 26%)。中位无进展生存期为4.0个月(95%可信区间:2.6-4.3),中位总生存期为11.1个月(95%可信区间:9.2-17.4)。在安全人群中,111例患者中有101例(91%)出现至少一次治疗相关不良事件,分别有39%和5.4%的患者出现至少一次3级和4级治疗相关不良事件。伏立诺他相关毒性促使66%的患者减少或中断剂量。全外显子组测序分析揭示了对治疗反应的几个潜在的预测性生物标志物。需要在更多患者中进行进一步的研究来验证这些发现。ClinicalTrials.gov识别码:NCT04357873。
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来源期刊
Nature cancer
Nature cancer Medicine-Oncology
CiteScore
31.10
自引率
1.80%
发文量
129
期刊介绍: Cancer is a devastating disease responsible for millions of deaths worldwide. However, many of these deaths could be prevented with improved prevention and treatment strategies. To achieve this, it is crucial to focus on accurate diagnosis, effective treatment methods, and understanding the socioeconomic factors that influence cancer rates. Nature Cancer aims to serve as a unique platform for sharing the latest advancements in cancer research across various scientific fields, encompassing life sciences, physical sciences, applied sciences, and social sciences. The journal is particularly interested in fundamental research that enhances our understanding of tumor development and progression, as well as research that translates this knowledge into clinical applications through innovative diagnostic and therapeutic approaches. Additionally, Nature Cancer welcomes clinical studies that inform cancer diagnosis, treatment, and prevention, along with contributions exploring the societal impact of cancer on a global scale. In addition to publishing original research, Nature Cancer will feature Comments, Reviews, News & Views, Features, and Correspondence that hold significant value for the diverse field of cancer research.
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