Medical Oncology Department, Centre François Baclesse, Anticipe Inserm U1086, Université Caen Normandie, Caen, France.
Medical Oncology Department, Institut Régional du Cancer de Montpellier (ICM), Montpellier, France.
Gynecol Oncol. 2022 Sep;166(3):389-396. doi: 10.1016/j.ygyno.2022.06.022. Epub 2022 Jul 26.
Anti-angiogenic rechallenge with bevacizumab plus chemotherapy is effective in recurrent ovarian cancer (rOC); however, data are limited on tyrosine kinase inhibitors after progression on maintenance bevacizumab.
In the randomized phase II TAPAZ trial, patients with rOC during the first year of bevacizumab maintenance therapy were assigned 2:1 to either weekly paclitaxel 65 mg/m plus pazopanib 600-800 mg daily or standard weekly paclitaxel 80 mg/m. The primary endpoint was 4-month progression-free survival (PFS) rate.
Overall, 116 patients were randomized and treated: 79 with combination therapy and 37 with single-agent paclitaxel. Median follow-up was 13.1 months. There was no difference between treatment arms in 4-month PFS rate (61% [95% CI, 51-73%] with the combination versus 68% [95% CI, 54-85%] with paclitaxel alone), median PFS (4.9 [95% CI, 4.1-6.1] versus 5.8 [95% CI, 4.8-7.4] months, respectively) or median overall survival (13.6 versus 12.9 months, respectively). The combination was associated with more grade 3/4 toxicities (87% versus 70%, respectively) and toxicity-related paclitaxel discontinuations (22% versus 11%). Pazopanib was discontinued for toxicity in 44% of patients, most commonly for gastrointestinal and vascular events. There were two treatment-related deaths, both in the combination arm (pulmonary embolism and gastrointestinal perforation). At month 4, patient-reported outcomes deteriorated from baseline in the combination arm, particularly for abdominal/gastrointestinal symptoms, which showed a clinically important difference versus paclitaxel alone.
In rOC progressing during maintenance bevacizumab, adding pazopanib to paclitaxel did not improve efficacy, increased toxicity, and compromised chemotherapy delivery.
govregistration:NCT02383251.
贝伐单抗联合化疗在复发性卵巢癌（rOC）中具有抗血管生成再挑战作用；然而，在贝伐单抗维持治疗进展后，关于酪氨酸激酶抑制剂的数据有限。
在随机的 II 期 TAPAZ 试验中，在贝伐单抗维持治疗的第一年期间发生 rOC 的患者按 2:1 随机分配至每周紫杉醇 65mg/m 加帕唑帕尼 600-800mg/d 或标准每周紫杉醇 80mg/m。主要终点是 4 个月无进展生存期（PFS）率。
共有 116 名患者随机分组并接受治疗：联合治疗组 79 例，单药紫杉醇组 37 例。中位随访时间为 13.1 个月。联合治疗组和单药紫杉醇组在 4 个月 PFS 率（联合治疗组 61%[95%CI，51-73%]，单药紫杉醇组 68%[95%CI，54-85%]）、中位 PFS（联合治疗组 4.9[95%CI，4.1-6.1]个月，单药紫杉醇组 5.8[95%CI，4.8-7.4]个月）或中位总生存期（联合治疗组 13.6 个月，单药紫杉醇组 12.9 个月）方面均无差异。联合治疗组发生更多 3/4 级毒性（分别为 87%和 70%）和与毒性相关的紫杉醇停药（分别为 22%和 11%）。44%的患者因毒性停用帕唑帕尼，最常见的是胃肠道和血管事件。联合治疗组有 2 例治疗相关死亡，均为肺栓塞和胃肠道穿孔。在第 4 个月时，联合治疗组的患者报告结局较基线恶化，特别是腹部/胃肠道症状，与单药紫杉醇相比，差异具有临床意义。
在贝伐单抗维持治疗期间进展的 rOC 中，将帕唑帕尼加入紫杉醇并未改善疗效，反而增加了毒性，并影响了化疗的实施。
govregistration:NCT02383251。
