Kim Stefano, Boustani Jihane, Vernerey Dewi, Vendrely Véronique, Evesque Ludovic, Francois Eric, Quero Laurent, Ghiringhelli Francois, de la Fouchardière Christelle, Dahan Laëtitia, Bouché Oliver, Chibaudel Benoist, Hajbi Farid El, Vernet Chloé, Rebucci-Peixoto Magali, Feuersinger Alexandra, Maritaz Christophe, Borg Christophe
Department of Medical Oncology, University Hospital of Besançon, Besançon, France.
Clinical Investigational Center, INSERM CIC-1431, Centre Hospitalier Universitaire de Besançon, Besançon, France.
Front Oncol. 2022 Aug 24;12:918499. doi: 10.3389/fonc.2022.918499. eCollection 2022.
Chemoradiotherapy alone is the standard treatment for locally advanced squamous cell anal carcinoma (SCAC). However, up to 50% of patients will experience recurrence; thus, there is a need for new treatments to improve outcomes. Modified docetaxel, cisplatin and 5-fluorouracil (mDCF) is a treatment option for first-line metastatic SCAC, having shown efficacy in the Epitopes-HPV01 and -02 trials (NCT01845779 and NCT02402842). mDCF treatment also plays a role in the modulation of anti-tumor immunity, suggesting it may be a good combination partner for immunotherapy in patients with SCAC. Anti-programmed death protein-1 (PD-1) immunotherapy has been shown to be effective in metastatic SCAC. We therefore designed the INTERACT-ION study to assess the combination of mDCF with ezabenlimab (BI 754091), an anti-PD-1 antibody, followed by chemoradiotherapy, in patients with Stage III SCAC.
INTERACT-ION is a pivotal, open-label, single-arm phase II study in patients with treatment-naïve Stage III SCAC. Patients will receive induction treatment with mDCF (docetaxel 40 mg/m and cisplatin 40 mg/m on Day 1, 5-fluorouracil 1200 mg/m/day for 2 days) every 2 weeks for 4 cycles and ezabenlimab (240 mg given intravenously) every 3 weeks for 3 cycles. In the absence of disease progression at 2 months, two additional cycles of mDCF and one additional cycle of ezabenlimab will be administered. Patients with radiological objective response, pathological complete/near-complete response and biological complete response will then receive an involved-node radiotherapy with intensity-modulated radiation therapy and concurrent chemotherapy, followed by ezabenlimab alone for seven cycles. All other patients will receive standard chemoradiotherapy. The primary endpoint is the clinical complete response rate 10 months after the first cycle of mDCF plus ezabenlimab. Major secondary endpoints are major pathological response and biological complete response after induction treatment. An extensive ancillary biomarker study in tumor tissue and peripheral blood will also be conducted.
The addition of immunotherapy to chemotherapy is an area of active interest in metastatic anal cancer. This pivotal study will evaluate this combination in the locally advanced setting. Ancillary biomarker studies will contribute to the understanding of predictors of response or resistance to treatment.
https://clinicaltrials.gov/ct2/show/NCT04719988, identifier NCT04719988.
单纯放化疗是局部晚期鳞状细胞肛管癌（SCAC）的标准治疗方法。然而，高达50%的患者会出现复发；因此，需要新的治疗方法来改善治疗效果。改良多西他赛、顺铂和5-氟尿嘧啶（mDCF）是一线转移性SCAC的一种治疗选择，已在Epitopes-HPV01和-02试验（NCT01845779和NCT02402842）中显示出疗效。mDCF治疗在抗肿瘤免疫调节中也发挥作用，这表明它可能是SCAC患者免疫治疗的良好联合伙伴。抗程序性死亡蛋白-1（PD-1）免疫治疗已被证明在转移性SCAC中有效。因此，我们设计了INTERACT-ION研究，以评估mDCF与抗PD-1抗体依扎贝林单抗（BI 754091）联合应用，随后进行放化疗，用于III期SCAC患者。
INTERACT-ION是一项针对未经治疗的III期SCAC患者的关键、开放标签、单臂II期研究。患者将接受诱导治疗，每2周进行1次mDCF（第1天多西他赛40mg/m²和顺铂40mg/m²，5-氟尿嘧啶1200mg/m²/天，共2天），共4个周期，每3周进行1次依扎贝林单抗（静脉注射240mg），共3个周期。如果在2个月时没有疾病进展，将再给予2个周期的mDCF和1个周期的依扎贝林单抗。有放射学客观反应、病理完全/接近完全反应和生物学完全反应的患者随后将接受调强放射治疗联合同步化疗的受累淋巴结放疗，然后单独使用依扎贝林单抗进行7个周期的治疗。所有其他患者将接受标准放化疗。主要终点是mDCF加依扎贝林单抗第一个周期后10个月的临床完全缓解率。主要次要终点是诱导治疗后的主要病理反应和生物学完全反应。还将在肿瘤组织和外周血中进行广泛的辅助生物标志物研究。
化疗联合免疫治疗是转移性肛管癌中一个备受关注的领域。这项关键研究将评估这种联合治疗在局部晚期情况下的效果。辅助生物标志物研究将有助于了解治疗反应或耐药的预测因素。
https://clinicaltrials.gov/ct2/show/NCT04719988，标识符NCT04719988。
