无种系BRCA1和/或BRCA2突变的铂敏感复发卵巢癌患者的维持奥拉帕尼单药治疗：OPINION试验的最终总生存结果

IF 4.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology Pub Date : 2025-04-28 DOI:10.1016/j.ygyno.2025.04.580

Andrés Poveda , Stéphanie Lheureux , Nicoletta Colombo , David Cibula , Mari Elstrand , Johanne Weberpals , Maria Bjurberg , Ana Oaknin , Magdalena Sikorska , Antonio González-Martín , Radoslaw Madry , María Jesus Rubio Pérez , Jonathan Ledermann , Ignacio Romero , Ozan Özgören , Alan Barnicle , Helen Marshall , Zahid Bashir , Erik Škof

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引用次数: 0

摘要

目的：在IIIb期、开放标签、单组、非比较药物、国际OPINION试验（NCT03402841）中，奥拉帕尼在无种系BRCA1和/或BRCA2突变（非gbrcam）的铂敏感复发卵巢癌患者中显示出无进展生存期的临床活性。我们报告最终总生存期（OS）；次要终点)，预先指定的次要终点更新和同源重组缺陷（HRD）和体细胞BRCAm （sBRCAm）状态的特别OS分析。方法非gbrcam铂敏感复发卵巢癌患者，既往铂基化疗≥2条线，在最后一次铂基化疗后接受300 mg奥拉帕尼片，每日2次，直到疾病进展或不可接受的毒性。结果279例患者入组治疗。中位OS随访期为33.1个月（数据截止日期为2021年9月17日），中位OS为32.7个月（95% CI 29.5-35.3）；24个月OS率为65.8%。在特设亚组分析中，hrd阳性肿瘤患者的OS率往往更高；在sBRCAm、hrd阳性包括sBRCAm、hrd阳性不包括sBRCAm和hrd阴性亚组中，24个月的OS率分别为81.5%、74.2%、72.0%和55.8%。82例（29.4%）患者报告了≥3级治疗后出现的不良事件，最常见的是贫血（13.6%）。总的来说，报告了2例骨髓增生异常综合征（自初步分析以来没有新病例）。结论：这些数据为奥拉帕尼作为非gbrcam铂敏感复发卵巢癌患者的维持治疗提供了额外的证据，在hrd阳性肿瘤中观察到更长的生存期。安全性与奥拉帕尼的初步分析和已知安全性一致，没有新的安全性发现。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Maintenance olaparib monotherapy in patients with platinum-sensitive relapsed ovarian cancer without a germline BRCA1 and/or BRCA2 mutation: Final overall survival results from the OPINION trial

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Maintenance olaparib monotherapy in patients with platinum-sensitive relapsed ovarian cancer without a germline BRCA1 and/or BRCA2 mutation: Final overall survival results from the OPINION trial

Objective

Maintenance olaparib demonstrated clinical activity for progression-free survival in patients without a germline BRCA1 and/or BRCA2 mutation (non-gBRCAm) who had platinum-sensitive relapsed ovarian cancer in the phase IIIb, open-label, single-arm, non-comparator, international OPINION trial (NCT03402841). We report final overall survival (OS; secondary endpoint), prespecified secondary endpoint updates and ad hoc OS analysis by homologous recombination deficiency (HRD) and somatic BRCAm (sBRCAm) status.

Methods

Patients with non-gBRCAm platinum-sensitive relapsed ovarian cancer, ≥2 prior lines of platinum-based chemotherapy, and in response following their last platinum-based chemotherapy received 300 mg olaparib tablets twice daily until disease progression or unacceptable toxicity.

Results

279 patients were enrolled and treated. With a median follow-up in patients censored for OS of 33.1 months (data cut-off September 17, 2021), median OS was 32.7 months (95 % CI 29.5–35.3); the 24-month OS rate was 65.8 %. In ad hoc subgroup analyses, OS rates tended to be higher in patients with HRD-positive tumors; 24-month OS rates were 81.5 %, 74.2 %, 72.0 % and 55.8 % in the sBRCAm, HRD-positive including sBRCAm, HRD-positive excluding sBRCAm, and HRD-negative subgroups, respectively. Grade ≥ 3 treatment-emergent adverse events were reported in 82 patients (29.4 %), most commonly anemia (13.6 %). Overall, two cases of myelodysplastic syndrome were reported (no new cases since the primary analysis).

Conclusion

These data provide additional evidence of olaparib as maintenance therapy in patients with non-gBRCAm platinum-sensitive relapsed ovarian cancer, with longer OS observed in those with HRD-positive tumors. The safety profile was consistent with the primary analysis and known safety profile of olaparib, with no new safety findings.

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来源期刊

Gynecologic oncology 医学-妇产科学

CiteScore

8.60

自引率

6.40%

发文量

1062

审稿时长

37 days

期刊介绍： Gynecologic Oncology, an international journal, is devoted to the publication of clinical and investigative articles that concern tumors of the female reproductive tract. Investigations relating to the etiology, diagnosis, and treatment of female cancers, as well as research from any of the disciplines related to this field of interest, are published. Research Areas Include: • Cell and molecular biology • Chemotherapy • Cytology • Endocrinology • Epidemiology • Genetics • Gynecologic surgery • Immunology • Pathology • Radiotherapy