编者按：CHAARTED研究显示，对于大多数转移性激素敏感性前列腺癌（HSPC）患者，早期采用化疗联合雄激素剥夺治疗（ADT+多西他赛）可显著提高生存率。然而，大多数患者会发展为去势抵抗性前列腺癌（CRPC），并需要额外的系统治疗。2024年美国临床肿瘤学会年会（ASCO 2024）最新进展（LBA）报告中，来自威斯康星大学Carbone癌症中心的Christos Kyriakopoulos教授分享了卡巴他赛联合阿比特龙治疗转移性前列腺癌的CHAARTED2临床研究结果。《肿瘤瞭望》就CRPC的治疗选择特邀采访Christos Kyriakopoulos教授。

 

Christos Kyriakopoulos教授：对于mCRPC的治疗取决于患者在去势敏感期接受的治疗。对于那些已经接受过化疗加阿比特龙、达罗他胺或其他第二代雄激素受体（AR）抑制剂的患者，二线治疗选择包括卡巴他赛或镥177（Lutetium 177-PSMA），二者在这一情况下都显示出显著的活性。对于具有特定突变的患者，例如BRCA1或BRCA2，PARP抑制剂是一个很好的选择。此外，对于具有微卫星不稳定性的患者，帕博利珠单抗也是一个选项。

 

Oncology Frontier:What are the current treatment strategies for patients with metastatic castration-resistant prostate cancer(mCRPC)?

 

Dr.Christos Kyriakopoulos:The treatment for mCRPC varies depending on what the patient has received for castration-sensitive disease.For those who have already received chemotherapy plus abiraterone，darolutamide，or other second-generation AR inhibitors，options for second-line treatment include cabazitaxel or lutetium，both of which have shown significant activity in this setting.For patients with specific mutations，such as BRCA1 or BRCA2，PARP inhibitors are an excellent choice.Additionally，for those with microsatellite instability，pembrolizumab is an option.

 

Christos Kyriakopoulos教授：对于这些患者我们通常会考虑化疗，具体取决于他们的整体状况和症状。虽然目前尚未批准在化疗前使用镥，但对于不适合化疗的特定患者可以考虑。基于患者的分子特征，也可选择PARP抑制剂。其他治疗方式如镭-223和sipuleucel-T疫苗也可供选择。

 

Oncology Frontier:How do you approach treatment for patients who have not received chemotherapy in the castration-sensitive setting?

 

Dr.Christos Kyriakopoulos:For these patients，we often consider chemotherapy，depending on their overall condition and symptoms.Although lutetium is not currently approved in the pre-chemotherapy setting，it can be considered for very select patients who are not candidates for chemotherapy.PARP inhibitors also remain a viable option based on the patient’s molecular profile.Other treatments like radium-223 and sipuleucel-T are also available.

 

Christos Kyriakopoulos教授：由ECOG-ACRIN癌症研究小组和美国国立卫生研究院的国家癌症研究所（NCI）领导下的多个合作组共同进行的CHAARTED2研究显示，与单用阿比特龙相比，卡巴他赛与阿比特龙的联合治疗显著延长了无进展生存期（PFS）5个月（14.9个月[95%CI 9.9-18.6]vs 9.9个月[95%CI，7.0-12.6]，P=0.049；风险比<hr/>0.73，80%CI 0.59-0.90）。然而大多数患者在发展成CRPC时已经接触过第二代AR抑制剂，研究结果在临床上的应用可能有限。尽管如此，这项研究的积极结果仍然值得关注。

 

Oncology Frontier:You announced the results of the CHAARTED2 study at the ASCO annual meeting.Is the combination of cabazitaxel and abiraterone better than abiraterone alone?

 

Dr.Christos Kyriakopoulos:The CHAARTED2 study，conducted by ECOG-ACRIN in collaboration with various cooperative groups under the leadership of the NCI，showed that the combination of cabazitaxel with abiraterone significantly prolonged progression-free survival by five months compared to abiraterone alone.However，this study was designed in a different era，and its applicability to current practice might be limited as most patients now have been exposed to second-generation AR inhibitors by the time they develop castration-resistant disease.Despite this，the study’s positive outcome is noteworthy.

 

Christos Kyriakopoulos教授：总体而言，卡巴他赛与阿比特龙联合治疗是安全的。我们确实观察到更高程度的细胞减少，这是使用化疗所预期的。然而并未检测到新的安全信号。重要的是，大多数患者能够按计划完成所有六个周期的化疗，尽管约65%的患者需要调整治疗方案。

 

Oncology Frontier:How safe is cabazitaxel with abiraterone?

 

Dr.Christos Kyriakopoulos:Overall，the combination of cabazitaxel with abiraterone was safe.We did observe higher degrees of cytopenias，which is expected with chemotherapy use.However，no new safety signals were detected.Importantly，the majority of patients were able to complete all six cycles of chemotherapy as planned，although about 65%required treatment modifications.

 

Christos Kyriakopoulos教授：在CHAARTED2中包含了两项相关研究，一项是循环肿瘤细胞的分析，一项是使用氟化物PET成像的影像学生物标志物。这些结果虽然未在ASCO上呈现，但它们是正在进行的工作的一部分，我们希望在未来的会议上展示这些发现。此外，我们在三个不同时间点收集了血浆样本，并计划进一步分析这些样本。

 

Oncology Frontier:What research do you plan to conduct in the future to further screen the people who will benefit?

 

Dr.Christos Kyriakopoulos:we included two correlative studies within CHAARTED2:an analysis of circulating tumor cells and imaging biomarkers using sodium fluoride PET imaging.While these results were not presented at ASCO 2024，they are part of ongoing work，and we hope to present these findings at future meetings.Additionally，we collected plasma samples at three different time points and plan to conduct further analyses with these samples.