Thomas Aparicio, Centre Hospitalier Universitaire (CHU) Saint Louis, Assistance Public Hôpitaux de Paris (APHP), and Université Paris 7, Sorbonne Paris Cité; Julien Taieb, Hôpital Européen Georges Pompidou, Paris; Francois Ghiringhelli, Centre Georges-François Leclerc; Karine Le Malicot, Fédération Francophone de Cancérologie Digestive; Come Lepage, CHU Le Bocage, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) 1231, Dijon; Valérie Boige, Institut Gustave Roussy, Villejuif; Olivier Bouché, CHU Robert Debré, Reims; Jean-Marc Phelip, CHU Saint Etienne-Hôpital Nord, Saint Priest en Jarez; Eric François, Centre Antoine Lacassagne, Nice; Christian Borel, Paul Strauss Center, Strasbourg; Roger Faroux, Centre Hospitalier (CH) La Roche sur Yon, La Roche sur Yon; Laetitia Dahan, CHU La Timone, Aix-Marseille-University, Marseille; Stéphane Jacquot, Centre de Cancérologie du Grand Montpellier, Montpellier; Dominique Genet, Accompagnement de la Recherche Clinique Hospitalière (ARCH)/Polyclinique, Limoges; Faiza Khemissa, CH Saint Jean, Perpignan; Etienne Suc, Clinique Saint Jean du Languedoc, Toulouse; Françoise Desseigne, Centre Léon Bérard, Lyon; Patrick Texereau, CH Layne, Mont-De-Marsan; and Jaafar Bennouna, Institut de Cancérologie de l'Ouest, Saint Herblay, France.
J Clin Oncol. 2018 Mar 1;36(7):674-681. doi: 10.1200/JCO.2017.75.2931. Epub 2018 Jan 18.
Purpose Conflicting results are reported for maintenance treatment with bevacizumab during chemotherapy-free intervals (CFI) in metastatic colorectal cancer after induction chemotherapy. Patients and Methods In this open-label, phase III, randomized controlled trial, we compared the tumor control duration (TCD) observed with bevacizumab maintenance and with no treatment (observation) during CFI subsequent to induction chemotherapy with 12 cycles of fluorouracil, leucovorin, and irinotecan plus bevacizumab. After disease progression, the induction regimen was repeated for eight cycles, followed by a new CFI. Results From March 2010 to July 2013, 491 patients were randomly assigned. Disease progression or death occurred during induction chemotherapy in 85 patients (17%); 261 patients (53%) had at least one reinduction, 107 (22%) had two reinductions, and 56 (11%) had three or more reinductions. The median TCD was 15 months in both groups; the median progression-free survival (PFS) from randomization was 9.2 and 8.9 months in the maintenance group and observation groups, respectively. The TCD observed in both groups was higher compared with the TCD hypotheses of the trial. The median overall survival (OS) was 21.7 and 22.0 months in the maintenance and observation groups, respectively. In the per-protocol population, defined as patients with at least one reinduction after the first progression, the median duration of the first CFI was 4.3 months in both arms; the median TCD was 17.8 and 23.3 months ( P = .339), the median PFS was 9.9 and 9.5 months, and the median OS was 27.6 and 28.5 months in the maintenance and observation groups, respectively. Multivariable analysis revealed that female gender, WHO performance status ≥ 2, and unresected primary tumors were associated with a shorter TCD. Conclusion Bevacizumab maintenance monotherapy did not improve TCD, CFI duration, PFS, or OS.
目的 在转移性结直肠癌诱导化疗后，无化疗间期（CFI）中贝伐单抗维持治疗的疗效结果存在争议。
方法 在这项开放标签、III 期、随机对照试验中，我们比较了贝伐单抗维持治疗与 CFI 期间不治疗（观察）在诱导化疗后 12 个周期氟尿嘧啶、亚叶酸钙和伊立替康加贝伐珠单抗后的肿瘤控制持续时间（TCD）。疾病进展后，重复诱导方案 8 个周期，然后进入新的 CFI。
结果 2010 年 3 月至 2013 年 7 月，共 491 例患者被随机分配。85 例（17%）患者在诱导化疗期间发生疾病进展或死亡；261 例（53%）患者至少进行了一次再诱导，107 例（22%）患者进行了两次再诱导，56 例（11%）患者进行了三次或更多次再诱导。两组的中位 TCD 均为 15 个月；维持组和观察组的中位无进展生存期（PFS）分别为随机分组后 9.2 和 8.9 个月。两组的 TCD 均高于试验的 TCD 假设。维持组和观察组的中位总生存期（OS）分别为 21.7 个月和 22.0 个月。在按方案人群中，定义为第一次进展后至少进行一次再诱导的患者，两组的首次 CFI 中位持续时间均为 4.3 个月；中位 TCD 分别为 17.8 个月和 23.3 个月（P=0.339），中位 PFS 分别为 9.9 个月和 9.5 个月，中位 OS 分别为 27.6 个月和 28.5 个月。多变量分析显示，女性、世界卫生组织（WHO）体能状态≥2 级和未切除的原发肿瘤与 TCD 缩短相关。
结论 贝伐单抗单药维持治疗并未改善 TCD、CFI 持续时间、PFS 或 OS。
