Ferron Gwénaël, De Rauglaudre Gaëtan, Becourt Stéphanie, Delanoy Nicolas, Joly Florence, Lortholary Alain, You Benoît, Bouchaert Patrick, Malaurie Emmanuelle, Gouy Sebastien, Kaminsky Marie-Christine, Meunier Jérôme, Alexandre Jérôme, Berton Dominique, Dohollou Nadine, Dubot Coraline, Floquet Anne, Favier Laure, Venat-Bouvet Laurence, Fabbro Michel, Louvet Christophe, Lotz Jean-Pierre, Abadie-Lacourtoisie Sophie, Desauw Christophe, Del Piano Francesco, Leheurteur Marianne, Bonichon-Lamichhane Nathalie, Rastkhah Mansour, Follana Philippe, Gantzer Justine, Ray-Coquard Isabelle, Pujade-Lauraine Eric
Institut Claudius Regaud, Département de Chirurgie Oncologique, IUCT Oncopole, Toulouse, France.
Institut Sainte Catherine, Cancérologie Clinique, Avignon, France.
Gynecol Oncol. 2023 Mar;170:186-194. doi: 10.1016/j.ygyno.2023.01.008. Epub 2023 Jan 25.
The oral anti-angiogenic therapy nintedanib prolongs progression-free survival (PFS) when combined with chemotherapy after primary surgery for advanced epithelial ovarian cancer. The randomized phase II CHIVA trial evaluated the impact of combining nintedanib with neoadjuvant chemotherapy (NACT) for epithelial ovarian cancer.
Patients with newly diagnosed unresectable FIGO stage IIIC-IV epithelial ovarian cancer received 3-4 cycles of carboplatin plus paclitaxel every 3 weeks as NACT before interval debulking surgery (IDS), followed by 2-3 post-operative cycles. Patients were randomized 2:1 to receive either nintedanib 200 mg twice daily or placebo on days 2-21 every 3 weeks during NACT (omitting peri-operative cycles), and then as maintenance therapy for up to 2 years. The primary endpoint was PFS.
Between January 2013 and May 2015, 188 patients were randomized (124 to nintedanib, 64 to placebo). PFS was significantly inferior with nintedanib (median 14.4 versus 16.8 months with placebo; hazard ratio 1.50, p = 0.02). Overall survival (OS) was also inferior (median 37.7 versus 44.1 months, respectively; hazard ratio 1.54, p = 0.054). Nintedanib was associated with increased toxicity (grade 3/4 adverse events: 92% versus 69%, predominantly hematologic and gastrointestinal), lower response rate by RECIST (35% versus 56% before IDS), and lower IDS feasibility (58% versus 77%) versus placebo.
Adding nintedanib to chemotherapy and in maintenance as part of NACT for advanced epithelial ovarian cancer cannot be recommended as it increases toxicity and compromises chemotherapy efficacy (IDS, PFS, OS).
govregistration: NCT01583322.
口服抗血管生成疗法尼达尼布与晚期上皮性卵巢癌初次手术后的化疗联合应用时可延长无进展生存期（PFS）。随机II期CHIVA试验评估了尼达尼布与新辅助化疗（NACT）联合用于上皮性卵巢癌的影响。
新诊断为不可切除的国际妇产科联盟（FIGO）IIIC-IV期上皮性卵巢癌患者在间隔减瘤手术（IDS）前每3周接受3-4个周期的卡铂加紫杉醇作为NACT，随后进行2-3个术后周期。患者按2:1随机分组，在NACT期间（不包括围手术期周期）每3周的第2-21天接受每日两次200 mg尼达尼布或安慰剂治疗，然后作为维持治疗长达2年。主要终点是PFS。
2013年1月至2015年5月期间，188例患者被随机分组（124例接受尼达尼布，64例接受安慰剂）。尼达尼布组的PFS明显较差（中位数分别为14.4个月和安慰剂组的16.8个月；风险比1.50，p = 0.02）。总生存期（OS）也较差（中位数分别为37.7个月和44.1个月；风险比1.54，p = 0.054）。与安慰剂相比，尼达尼布与毒性增加相关（3/4级不良事件：92%对69%，主要是血液学和胃肠道不良事件），根据实体瘤疗效评价标准（RECIST）的缓解率较低（IDS前为35%对56%），IDS可行性较低（58%对77%）。
不建议在晚期上皮性卵巢癌的化疗中添加尼达尼布并作为NACT的一部分进行维持治疗，因为这会增加毒性并损害化疗疗效（IDS、PFS、OS）。
美国国立医学图书馆（gov）注册编号：NCT01583322。
