Peter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
Department of Medical Oncology, Prince of Wales Hospital and Royal Hospital for Women, Randwick, New South Wales, Australia.
Int J Gynecol Cancer. 2022 Jul 4;32(7):906-912. doi: 10.1136/ijgc-2021-003009.
OBJECTIVES: The primary objective of this study was to describe treatment patterns after poly-ADP ribose polymerase (PARP) inhibitor in patients with epithelial ovarian cancer. Secondary objectives were to evaluate duration of response, time to first subsequent therapy, progression-free survival and overall survival. METHODS: This was a retrospective analysis of patients with epithelial ovarian cancer treated with PARP inhibitor therapy at six Australian gynecological oncology centers. Eligible patients were identified via clinics, trial databases and pharmacy dispensing logs between January 2005 and September 2019. Information regarding clinico-pathological characteristics and treatment outcomes were collated from medical records. RESULTS: A total of 85 patients with epithelial ovarian cancer were identified. Of these, 61% had germline mutations, 9% had somatic mutations, 5% had confirmed homologous recombination deficiency and 25% were wildtype mutations. A total of seventy-seven (91%) patients received chemotherapy after PARP inhibitor, with fifty-six (72.7%) of these patients receiving platinum-based chemotherapy. Four patients (5%) had a complete response, 15 (20%) a partial response, 15 (20%) stable disease and 41 (55%) progressive disease. Median duration of response to chemotherapy was 7.0 months (range 0.2-20.4). Median time to first subsequent therapy was 17.6 and 15.1 months in patients who received a PARP inhibitor as maintenance therapy and treatment, respectively. Median progression-free survival of first line treatment after PARP inhibitor was 9.6, 3.5 and 4.6 months for platinum doublet, single agent platinum and non-platinum chemotherapy, respectively. Adjusting for age and FIGO (Federation of Gynecological Oncologists classification) stage progression-free survival did not differ between treatment groups (p=0.14). Median overall survival for the cohort was 69 months, and patients with platinum sensitive ovarian cancer had improved survival compared with those with platinum refractory or resistant disease. CONCLUSION: Platinum doublet chemotherapy resulted in non-significant improved progression-free survival compared with other regimens, suggesting potential independent mechanisms of resistance between PARP inhibitor and platinum compounds.
目的：本研究的主要目的是描述上皮性卵巢癌患者接受聚 ADP 核糖聚合酶（PARP）抑制剂治疗后的治疗模式。次要目标是评估缓解持续时间、首次后续治疗时间、无进展生存期和总生存期。
方法：这是对 6 家澳大利亚妇科肿瘤中心接受 PARP 抑制剂治疗的上皮性卵巢癌患者进行的回顾性分析。通过诊所、试验数据库和药房配药记录，于 2005 年 1 月至 2019 年 9 月期间确定符合条件的患者。从病历中收集临床病理特征和治疗结果信息。
结果：共确定了 85 例上皮性卵巢癌患者。其中，61%有胚系 突变，9%有体细胞 突变，5%有同源重组缺陷确认，25%为 野生型突变。77 例（91%）患者在接受 PARP 抑制剂治疗后接受化疗，其中 56 例（72.7%）患者接受铂类化疗。4 例（5%）患者有完全缓解，15 例（20%）有部分缓解，15 例（20%）病情稳定，41 例（55%）病情进展。化疗缓解的中位持续时间为 7.0 个月（范围 0.2-20.4）。接受 PARP 抑制剂维持治疗和治疗的患者首次后续治疗的中位时间分别为 17.6 个月和 15.1 个月。PARP 抑制剂后一线治疗的中位无进展生存期分别为铂类双药、单药铂类和非铂类化疗的 9.6、3.5 和 4.6 个月。调整年龄和 FIGO（妇科肿瘤学家联合会分类）分期后，各组之间的无进展生存期无差异（p=0.14）。该队列的中位总生存期为 69 个月，铂类敏感卵巢癌患者的生存时间优于铂类耐药或抵抗疾病患者。
结论：与其他方案相比，铂类双药化疗并未显著改善无进展生存期，这表明 PARP 抑制剂和铂类化合物之间可能存在独立的耐药机制。
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