编者按：卵巢癌因其早期诊断率低，经传统治疗后易复发，使其成为妇科恶性肿瘤中预后最差的一种。近年来，随着聚腺苷二磷酸核糖聚合酶（PARP）抑制剂的出现和广泛应用于临床，有效地延长了晚期卵巢癌患者的无进展生存期，改变了卵巢癌的治疗格局。2023年欧洲肿瘤内科学会亚洲年会（ESMO ASIA 2023）于近日在新加坡召开，在优选口头报告和微型口头报告混合专场，印度塔塔医疗中心的Somnath Roy教授分享了“在种系BRCA突变或HRD阳性的新诊断晚期卵巢癌患者中，PARP抑制剂±贝伐珠单抗维持治疗的真实世界用药经验”，《肿瘤瞭望》现场有幸采访到Somnath Roy教授，请他就基因检测在卵巢癌中的作用、本次研究的重要结果以及PARP抑制剂不良反应的管理进行深入介绍。

 

Somnath Roy医学博士

印度塔塔医疗中心肿瘤内科

Somnath Roy教授：种系BRCA检测在卵巢恶性肿瘤中发挥着关键作用，对治疗、诊断和预测均有重要意义。种系BRCA阳性的个体患BRCA相关癌症的可能性更高，包括乳腺癌和其他妇科癌症。因此，应该进行筛查，尤其是对于那些有这些癌症家族史的人。此外，对种系BRCA阳性者的家庭成员提供咨询和一级亲属检测至关重要。对于这些个体，建议采取全面的筛查措施，如乳腺钼钯（X光）检查和乳腺磁共振。在我们的研究中，种系BRCA阳性患者占28%，这表明有很大一部分高危人群需要进行积极筛查。

 

种系BRCA检测对卵巢癌的治疗具有深远意义。在维持治疗中使用PARP抑制剂在无进展和总生存率方面均显示出显著获益，如SOLO-1等试验所证明的那样。另一个关键方面是同源重组修复缺陷（HRD）检测。这一新概念涉及评估基因组疤痕，尤其是与亚洲人群相关的基因组疤痕。对于HRD阳性患者，贝伐珠单抗联合PARP抑制剂作为维持治疗可显著减少复发，并改善无进展生存。因此，HRD和BRCA检测在卵巢癌（包括非BRCA相关基因突变）管理中至关重要。

 

Oncology Frontier:Dr.Roy，could you describe the role of germline and tumor testing in the treatment of ovarian cancer?

 

Dr.Somnath Roy:Germline BRCA testing plays a pivotal role in ovarian malignancy，with implications for therapy，diagnosis，and prediction.Individuals who are germline BRCA positive have a higher likelihood of developing BRCA-related cancers，including breast cancer and other gynecological cancers.It’s imperative to perform screenings，especially for those with a family history of these cancers.Additionally，family counseling and testing of first-degree relatives are crucial for those with a germline BRCA positive status.For these individuals，comprehensive screening measures like mammography and breast MRI scans are recommended.In our study，28 percent of the patients were germline BRCA positive，indicating a significant portion of high-risk individuals who require proactive screening.

 

The therapeutic implications of germline BRCA in ovarian cancer are profound.The use of PARP inhibitors in maintenance therapy has shown remarkable benefits in terms of progression-free and overall survival，as evidenced in trials like SOLO-1.Another critical aspect is HRD(Homologous Recombination Deficiency)testing.This newer concept involves assessing genomic scars，particularly relevant in Asian populations.For HRD-positive patients，combining bevacizumab with PARP inhibitors as maintenance therapy can significantly reduce recurrence and improve progression-free survival.Therefore，HRD and BRCA testing are essential in managing ovarian cancer，including non-BRCA associated gene mutations.

 

Somnath Roy教授：我们的研究重点是PARP抑制剂联合贝伐珠单抗在真实世界亚洲人群中的使用，该人群在许多随机试验中代表性不足。考虑到经济限制和毒性管理，我们假设使用较低剂量的PARP抑制剂。尽管样本量小、随访时间短，但我们的研究表明，2年无进展生存率（PFS）为82%。这种方法似乎可以维持较低剂量PARP抑制剂的疗效，但有必要进一步研究，以证实在这些较低剂量的基础上添加贝伐珠单抗的有效性，特别是在HRD阳性或种系BRCA阳性亚组中。

 

Oncology Frontier:Can you share the findings from your research on maintenance PARP inhibitor plus/minus bevacizumab?

 

Dr.Somnath Roy:Our study focused on the real-world application of PARP inhibitors combined with bevacizumab in the Asian population，a demographic not well represented in many randomized trials.Given the economic constraints and toxicity management，we hypothesized the use of lower doses of PARP inhibitors.Despite the small sample size and short follow-up，our study indicated a progression-free survival(PFS)rate of 82 percent at two years.This approach seems to maintain the efficacy of lower doses of PARP inhibitors，but further research is necessary to confirm the effectiveness of adding bevacizumab to these reduced doses，particularly in HRD positive or germline BRCA positive subgroups.

 

Somnath Roy教授：在我们的研究中观察到的毒性与随机试验中报告的一致，主要为血液血毒性，如贫血和血小板减少、疲劳、恶心、呕吐和转氨酶升高。大多数不良反应为轻度至中度。我们的研究结果表明，较低剂量的PARP抑制剂联合贝伐珠单抗不会导致显著的严重不良反应。这种方法也与随机试验中报告的副作用情况一致。

 

Oncology Frontier:With the widespread application of PARP inhibitors，how do you manage their adverse reactions?

 

Dr.Somnath Roy:The toxicities observed in our study align with those reported in randomized trials.They primarily include hematological toxicities like anemia and thrombocytopenia，fatigue，nausea，vomiting，and transaminitis.Most adverse effects are mild to moderate.Our findings suggest that using lower doses of PARP inhibitors with bevacizumab does not lead to significant severe adverse effects.This approach also aligns with the side effect profiles reported in randomized trials.