Royal Marsden NHS Foundation Trust, London, UK.
Cancer Research UK & UCL Cancer Trials Centre, London, UK.
Gynecol Oncol. 2019 Jun;153(3):541-548. doi: 10.1016/j.ygyno.2019.03.256. Epub 2019 Apr 18.
We evaluated four different treatment regimens for advanced-stage mucinous epithelial ovarian cancer.
We conducted a multicenter randomized factorial trial (UK and US). Patients were diagnosed with primary mEOC: FIGO stage II-IV or recurrence after stage I disease. Treatment arms were paclitaxel-carboplatin, oxaliplatin-capecitabine, paclitaxel-carboplatin-bevacizumab, or oxaliplatin-capecitabine-bevacizumab. Chemotherapy was given 3-weekly for 6 cycles, and bevacizumab (3-weekly) was continued as maintenance (for 12 cycles). Endpoints included overall-survival (OS), progression-free survival (PFS), toxicity and quality of life (QoL).
The trial stopped after 50 patients were recruited due to slow accrual. Median follow-up was 59 months. OS hazard ratios (HR) for the two main comparisons were: 0.78 (p = 0.48) for Oxal-Cape vs. Pac-Carbo (each with/without bevacizumab), and 1.04 (p = 0.92) for bevacizumab vs. no bevacizumab. Corresponding PFS HRs were: 0.84 and 0.80. Retrospective central pathology review revealed only 45% (18/40) cases with available material had confirmed primary mEOC. Among these, OS HR for Oxal-Cape vs. Pac-Carbo was 0.36 (p = 0.14); PFS HR = 0.62 (p = 0.40). Grade 3-4 toxicity was seen in 61% Pac-Carbo, 61% Oxal-Cape, 54% Pac-Carbo-Bev, and 85% Oxal-Cape-Bev. QoL was similar between the four arms.
mEOC/GOG0241 represents an example of a randomized rare tumor trial. Logistical challenges led to early termination, including difficulties in local histopathological diagnosis and accessing drugs outside their labelled indication. There was misalignment between central funders who support clinical trials in rare cancers and the deprioritisation of such work by those managing and funding research at a local level. Rare cancer trials should include centralised pathology review before treatment. Clinical trial registry number: ISRCTN83438782.
我们评估了晚期黏液性卵巢上皮癌的四种不同治疗方案。
我们进行了一项多中心随机析因试验（英国和美国）。患者被诊断为原发性 mEOC：FIGO 分期 II-IV 期或 I 期疾病复发。治疗臂为紫杉醇-卡铂、奥沙利铂-卡培他滨、紫杉醇-卡铂-贝伐珠单抗或奥沙利铂-卡培他滨-贝伐珠单抗。化疗每 3 周进行 6 个周期，贝伐珠单抗（每 3 周）作为维持治疗（12 个周期）。终点包括总生存期（OS）、无进展生存期（PFS）、毒性和生活质量（QoL）。
由于入组速度缓慢，试验在招募了 50 名患者后停止。中位随访时间为 59 个月。两项主要比较的 OS 风险比（HR）分别为：奥沙利铂-卡培他滨与紫杉醇-卡铂（均有/无贝伐珠单抗）的 0.78（p=0.48），贝伐珠单抗与无贝伐珠单抗的 1.04（p=0.92）。相应的 PFS HR 分别为 0.84 和 0.80。回顾性中心病理复查显示，仅有 45%（18/40）有可用材料的病例证实为原发性 mEOC。在这些病例中，奥沙利铂-卡培他滨与紫杉醇-卡铂的 OS HR 为 0.36（p=0.14）；PFS HR=0.62（p=0.40）。紫杉醇-卡铂、奥沙利铂-卡培他滨、紫杉醇-卡铂-贝伐珠单抗和奥沙利铂-卡培他滨-贝伐珠单抗的 3-4 级毒性发生率分别为 61%、61%、54%和 85%。四个臂之间的 QoL 相似。
mEOC/GOG0241 代表了一项随机罕见肿瘤试验的例子。由于当地病理诊断方面的困难以及获取药物超出其标签适应症的困难，导致了后勤方面的挑战，最终导致试验提前终止。中央资助者和地方管理及资助研究人员之间存在错位，前者支持罕见癌症临床试验，而后者却不重视这类工作。罕见癌症试验应在治疗前进行中央病理复查。临床试验注册号：ISRCTN83438782。
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