奥拉帕利治疗 BRCA 突变和同源重组缺陷状态的铂敏感复发性卵巢癌：LIGHT 研究 II 期初步分析。
Olaparib treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency status: Phase II LIGHT study primary analysis.
机构信息
Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical College, New York, NY, USA,.
Department of Obstetrics and Gynecology, Jordan Center for Gynecologic Oncology at the Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
出版信息
Gynecol Oncol. 2022 Sep;166(3):425-431. doi: 10.1016/j.ygyno.2022.06.017. Epub 2022 Jul 5.
OBJECTIVE
Olaparib treatment resulted in significant improvement in objective response rates (ORRs) and progression-free survival (PFS) over non‑platinum chemotherapy in patients with BRCA1/BRCA2-mutated (BRCAm) platinum-sensitive relapsed ovarian cancer (PSROC) and ≥2 prior lines of platinum-based chemotherapy in the phase III SOLO3 study. LIGHT (NCT02983799) prospectively evaluated olaparib treatment for patients with PSROC and known BRCAm and homologous recombination deficiency (HRD) status.
METHODS
In this phase II open-label multicenter study, patients with PSROC and ≥1 prior line of platinum-based chemotherapy were assigned to cohorts by presence of germline BRCAm (gBRCAm), somatic BRCAm (sBRCAm), HRD-positive tumors without BRCAm, or HRD-negative tumors. The primary endpoint was investigator-assessed ORR. Secondary endpoints included disease control rate (DCR) and PFS. Tumors were analyzed using Myriad BRACAnalysis CDx and myChoice HRD assays; HRD-positive tumors were defined using a genomic instability score of ≥42.
RESULTS
Of 272 enrolled patients, 271 received olaparib and 270 were included in efficacy analyses. At data cut-off, ORRs in the gBRCAm, sBRCAm, HRD-positive, and HRD-negative cohorts were 69.3%, 64.0%, 29.4%, and 10.1%, respectively. DCRs were 96.0%, 100.0%, 79.4%, and 75.3% in each cohort, respectively. Median PFS was 11.0, 10.8, 7.2, and 5.4 months, respectively. The most common (≥ 20%) treatment-emergent adverse events included nausea, fatigue/asthenia, vomiting, anemia, constipation, diarrhea, and decreased appetite.
CONCLUSIONS
Olaparib treatment demonstrated activity across all cohorts. The greatest efficacy was observed in the BRCAm cohorts, regardless of gBRCAm/sBRCAm. For patients without a BRCAm, greater efficacy was observed in the HRD-positive than the HRD-negative cohorts. The safety profile was consistent with that established in previous olaparib studies.
目的
在 SOLO3 研究中，奥拉帕利治疗 BRCA1/BRCA2 突变（BRCAm）铂敏感复发性卵巢癌（PSROC）患者和既往接受过≥2 线铂类化疗的患者，与非铂类化疗相比，显著提高了客观缓解率（ORR）和无进展生存期（PFS）。LIGHT（NCT02983799）前瞻性评估了奥拉帕利治疗 PSROC 且已知 BRCAm 和同源重组缺陷（HRD）状态的患者。
方法
在这项开放标签、多中心的 II 期研究中，根据是否存在胚系 BRCAm（gBRCAm）、体细胞 BRCAm（sBRCAm）、无 BRCAm 的 HRD 阳性肿瘤或 HRD 阴性肿瘤，将 PSROC 且既往接受过≥1 线铂类化疗的患者分配到不同的队列。主要终点为研究者评估的 ORR。次要终点包括疾病控制率（DCR）和 PFS。使用 Myriad BRACAnalysis CDx 和 myChoice HRD 检测进行肿瘤分析；HRD 阳性肿瘤定义为基因组不稳定性评分≥42。
结果
在 272 名入组患者中，271 名接受了奥拉帕利治疗，270 名患者纳入疗效分析。在数据截止时，gBRCAm、sBRCAm、HRD 阳性和 HRD 阴性队列的 ORR 分别为 69.3%、64.0%、29.4%和 10.1%。各队列的 DCR 分别为 96.0%、100.0%、79.4%和 75.3%。中位 PFS 分别为 11.0、10.8、7.2 和 5.4 个月。最常见（≥20%）的治疗相关不良事件包括恶心、疲劳/乏力、呕吐、贫血、便秘、腹泻和食欲下降。
结论
奥拉帕利治疗在所有队列中均显示出疗效。在 BRCAm 队列中观察到最大疗效，无论 gBRCAm/sBRCAm 如何。对于没有 BRCAm 的患者，HRD 阳性队列的疗效优于 HRD 阴性队列。安全性与先前奥拉帕利研究一致。
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