Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, China.
Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, China.
BMC Med. 2024 Oct 29;22(1):496. doi: 10.1186/s12916-024-03697-1.
Neoadjuvant chemotherapy may be considered for patients with ovarian cancer (OC) whose tumors are deemed unlikely to be completely cytoreduced to no gross residual disease (R0) or who are poor surgical candidates. This Ib/II study was designed to assess the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin as neoadjuvant chemotherapy for stages III-IV, unresectable OC.
Eligible patients with stage III-IV, unresectable OC were enrolled in this phase Ib/II study. All patients received neoadjuvant nab-paclitaxel (260 mg/m, day 1, every 3 weeks) plus carboplatin (AUC 5, day 1, every 3 weeks) for 3 cycles before surgery, followed by 3-6 cycles of adjuvant chemotherapy. The phase Ib primary endpoint was safety; the phase II primary endpoint was the R0 resection rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety (for all populations).
Sixty-two patients were enrolled and were given neoadjuvant therapy treated between October 2019 and December 2020, of whom 9 were in the phase Ib portion and 53 in the phase II portion. A total of 53 patients underwent surgery with an R0 resection rate of 73.6% (95% CI, 59.7-84.7%). With a median follow-up of 17.5 (range 0.7-36.7) months, for all patients, the best ORR was 83.9% (95% CI, 71.7-92.4%) with 47 partial responses, the median PFS was 18.6 (95% CI, 13.8-23.3%) months, and median OS was not reached. During the neoadjuvant chemotherapy, treatment-related adverse events (TRAEs) of any grade occurred in 91.9% (57/62) of all patients. The most common hematologic TRAEs were neutropenia (55/62, 88.7%), and non-hematologic toxicity was alopecia (36/62, 58.1%). Forty-nine patients (79.0%) experienced at least one grade 3-4 TRAEs, with the most common was neutropenia (44/62, 71.0%). Besides, delays in neoadjuvant chemotherapy and surgery due to AEs were observed in 9 (1 in phase Ib; 8 in phase II) and 7 (phase II) patients, respectively.
The study demonstrated an encouraging efficacy and manageable safety profile of neoadjuvant chemotherapy nab-paclitaxel plus carboplatin in stage III-IV, unresectable OC. In addition, AEs resulting in chemotherapy and surgery delays should be cautiously considered in this clinical setting.
ClinicalTrials.gov, ChiCTR1900026893. Registered at 25 October 2019.
对于肿瘤不太可能完全减灭至无肉眼残留病灶（R0）或手术条件差的卵巢癌（OC）患者，可考虑新辅助化疗。本 Ib/II 期研究旨在评估纳米白蛋白结合紫杉醇（nab-紫杉醇）联合卡铂作为 III-IV 期不可切除 OC 的新辅助化疗的疗效和安全性。
本 Ib/II 期研究纳入了 III-IV 期不可切除的 OC 患者。所有患者均接受新辅助 nab-紫杉醇（260 mg/m，第 1 天，每 3 周）+卡铂（AUC 5，第 1 天，每 3 周）治疗 3 个周期，然后进行 3-6 个周期的辅助化疗。Ib 期的主要终点为安全性；II 期的主要终点为 R0 切除率。次要终点为无进展生存期（PFS）、总生存期（OS）、客观缓解率（ORR）和安全性（所有人群）。
2019 年 10 月至 2020 年 12 月期间共纳入 62 例患者接受新辅助治疗，其中 9 例入 Ib 期，53 例入 II 期。53 例患者接受了手术，R0 切除率为 73.6%（95%CI，59.7-84.7%）。中位随访 17.5 个月（范围 0.7-36.7），所有患者的最佳 ORR 为 83.9%（95%CI，71.7-92.4%），包括 47 例部分缓解，中位 PFS 为 18.6 个月（95%CI，13.8-23.3%），中位 OS 尚未达到。在新辅助化疗期间，所有患者（62 例）中 91.9%（57/62）发生了任何级别的治疗相关不良事件（TRAEs）。最常见的血液学 TRAEs 为中性粒细胞减少（55/62，88.7%），非血液学毒性为脱发（36/62，58.1%）。49 例（79.0%）患者发生至少 1 次 3-4 级 TRAEs，最常见的为中性粒细胞减少（44/62，71.0%）。此外，9 例（Ib 期 1 例；II 期 8 例）和 7 例（II 期）患者因 AE 导致新辅助化疗和手术延迟。
该研究表明，在 III-IV 期不可切除的 OC 中，nab-紫杉醇联合卡铂新辅助化疗具有令人鼓舞的疗效和可管理的安全性。此外，在这种临床环境下，应谨慎考虑因 AE 导致的化疗和手术延迟。
ClinicalTrials.gov，ChiCTR1900026893。于 2019 年 10 月 25 日注册。
