编者按：在2026年美国临床肿瘤学会泌尿生殖系统肿瘤研讨会（ASCO GU）上，复发难治性生殖细胞肿瘤的治疗突破成为泌尿肿瘤领域的关注焦点。肿瘤瞭望-泌尿时讯特邀印第安纳大学医学院Jennifer King教授，围绕其团队公布的核心研究数据、泌尿生殖肿瘤领域的前沿趋势与未来发展方向，展开了深度专访。

01

请您为我们简要介绍下您和团队在本次ASCO GU大会上公布的核心研究内容，以及该研究为复发难治性生殖细胞肿瘤领域带来的关键进展与临床实践价值？

Jennifer King 教授：我们团队开展了一项单臂II期临床试验，旨在评估多靶点酪氨酸激酶抑制剂卡博替尼，用于复发难治性生殖细胞肿瘤（GCT）患者的疗效与安全性。

生殖细胞肿瘤是一类好发于青壮年的恶性肿瘤，尽管一线含铂化疗方案可使多数患者实现临床治愈，但仍有约20%的患者一线治疗后出现疾病复发；而在复发患者中，又有约50%的人群接受挽救性化疗、手术等治疗后仍会出现疾病进展。这部分多线治疗失败的患者，临床治疗选择极为有限，存在巨大的未被满足的临床需求。从生物学机制来看，血管内皮生长因子（VEGF）介导的血管生成、c-MET通路异常激活，在生殖细胞肿瘤的发生发展、侵袭转移及耐药进程中发挥着关键作用；而卡博替尼可同时靶向VEGFR与c-MET等多个肿瘤进展关键靶点，这也是我们选择在该难治人群中开展卡博替尼临床研究的核心理论依据。

本项研究为单臂II期临床试验，研究纳入标准治疗失败的复发难治性生殖细胞肿瘤患者44例，给予卡博替尼60mg每日一次口服给药，治疗持续至患者出现疾病进展或不可耐受的治疗相关毒性。研究预设的主要终点为临床获益率（CBR），定义为治疗后达到完全缓解（CR）、部分缓解（PR），以及疾病稳定（SD）持续≥3个月的患者比例之和。研究最终结果显示，卡博替尼在该难治性患者群体中的临床获益率达到43.2%。这一结果具有里程碑式的临床意义—这是迄今为止，首个在多线治疗失败的复发难治性生殖细胞肿瘤患者中，被证实具有明确抗肿瘤疗效的非细胞毒性药物，打破了该人群长期以来仅能依赖细胞毒性化疗的治疗困境，为患者提供了全新的、毒性更可控的治疗选择。

Oncology Frontier: Thank you so much, Dr. King, for taking the time to accept our interview. First, could you briefly introduce the core research presented by you and your team at this ASCO-GU congress, as well as the key advances and clinical practice value it brings to the field of relapsed/refractory germ cell tumors?

Dr. Jennifer King: Our team conducted a single-arm phase II clinical trial to evaluate the efficacy and safety of cabozantinib, a multi-target tyrosine kinase inhibitor (TKI), in patients with relapsed/refractory germ cell tumors (GCTs).

Germ cell tumors are a group of malignancies that predominantly occur in young and middle-aged adults. Although first-line platinum-based chemotherapy regimens can achieve clinical cure in most patients, approximately 20% of patients experience disease relapse after first-line treatment. Among relapsed patients, around 50% will still develop disease progression after receiving salvage chemotherapy, surgery, and other available treatments. For this population who have failed multiple lines of therapy, clinical treatment options are extremely limited, and there is a huge unmet clinical need.

From a biological mechanism perspective, vascular endothelial growth factor (VEGF)-mediated angiogenesis and aberrant activation of the c-MET pathway play critical roles in the tumorigenesis, invasion, metastasis, and drug resistance progression of germ cell tumors. Cabozantinib can simultaneously target multiple key drivers of tumor progression, including VEGFR and c-MET, which is the core theoretical basis for our clinical trial of cabozantinib in this refractory patient population.

This single-arm phase II trial enrolled 44 patients with relapsed/refractory germ cell tumors who had failed standard-of-care treatment. Patients received cabozantinib 60 mg orally once daily, with treatment continued until disease progression or intolerable treatment-related toxicity. The prespecified primary endpoint of the study was clinical benefit rate (CBR), defined as the sum of the proportion of patients who achieved complete response (CR), partial response (PR), and stable disease (SD) lasting ≥3 months after treatment.

The final results of the study showed that cabozantinib achieved a clinical benefit rate of 43.2% in this refractory patient population. This result carries landmark clinical significance: it is the first non-cytotoxic agent to date proven to have definitive anti-tumor efficacy in patients with relapsed/refractory germ cell tumors who have failed multiple lines of therapy. It breaks the long-standing treatment dilemma where this population could only rely on cytotoxic chemotherapy, and provides a new treatment option with more controllable toxicity for patients.

02

本次ASCO GU大会覆盖了泌尿生殖系统肿瘤全领域的前沿探索，在您看来，本次大会所揭示的、未来将引领领域发展的核心临床研究趋势是什么？

Jennifer King 教授：我始终认为，以患者为中心的全程诊疗与管理模式，将是未来泌尿生殖肿瘤领域最为核心的发展方向。这一趋势主要体现在两个核心维度：其一，临床研究的设计与开展，需始终锚定对患者长期生存、生活质量最具临床价值的核心终点，真正解决患者的核心临床诉求；其二，在追求抗肿瘤疗效的同时，需持续聚焦治疗相关毒性的管控与降低，最大程度减少治疗对患者正常生理功能、生活质量的负面影响。

Oncology Frontier: Thank you for your wonderful interpretation. This ASCO-GU congress covers cutting-edge explorations across the full spectrum of genitourinary oncology. In your view, what are the core clinical research trends revealed by this congress that will lead the development of the field in the future?

Dr. Jennifer King: I have always believed that a patient-centered full-cycle diagnosis, treatment and management model will be the core development direction of genitourinary oncology in the future. This trend is mainly reflected in two core dimensions: first, the design and conduct of clinical trials must always be anchored to the core endpoints with the greatest clinical value for patients' long-term survival and quality of life, to truly address patients' core clinical needs; second, while pursuing anti-tumor efficacy, we must continuously focus on the management and mitigation of treatment-related toxicities, to minimize the negative impact of treatment on patients' normal physiological functions and quality of life.

03

本次大会公布了多项有望改写临床实践的重磅研究成果，在您看来，要推动这些前沿治疗方案更快、更规范地落地临床，真正惠及广大患者，当前面临的核心机遇与挑战分别是什么？

Jennifer King 教授：谈及前沿方案向临床实践的转化，核心的机遇与挑战均围绕真实世界的临床诊疗场景展开。当前我们面临的核心挑战主要有两点：第一，医疗服务的可及性仍是亟待突破的重大难题，如何让所有有治疗需求的患者，都能公平地接触并接受前沿的标准治疗方案，是全球肿瘤领域共同面对的问题；第二，临床医生的诊疗时间资源存在显著缺口，我们需要充足的时间与患者进行充分的医患沟通，完整梳理患者的病情数据，为患者清晰、全面地解读诊疗方案的获益与风险，从而帮助患者做出最适合自身的临床决策。而临床中巨大的未被满足的治疗需求，正是我们推动前沿方案落地的核心机遇，也持续驱动着领域内多方力量协同发力，加速研究成果向临床实践的转化与规范化推广。

Oncology Frontier: This congress has announced a number of landmark research results that are expected to rewrite clinical practice. In your opinion, what are the core opportunities and challenges currently faced to promote the faster and more standardized translation of these cutting-edge treatment regimens into clinical practice to truly benefit the majority of patients?

Dr. Jennifer King: When it comes to the translation of cutting-edge regimens into clinical practice, the core opportunities and challenges all revolve around real-world clinical practice settings. At present, the core challenges we face are mainly twofold: first, access to medical care remains a major urgent problem to be solved. How to enable all patients in need of treatment to have equitable access to cutting-edge standard treatment regimens is a common issue faced by the global oncology community. Second, there is a significant gap in clinicians' time resources for diagnosis and treatment. We need sufficient time to conduct thorough doctor-patient communication with patients, fully sort out patients' medical history data, and clearly and comprehensively interpret the benefits and risks of diagnosis and treatment regimens for patients, so as to help patients make the most appropriate clinical decisions for themselves.

The huge unmet clinical treatment needs in practice are the core opportunity for us to promote the implementation of cutting-edge regimens, and also continuously drive the collaborative efforts of multiple stakeholders in the field to accelerate the translation and standardized promotion of research results into clinical practice.

04

未来几年内，哪一项研究突破或发展方向，最有可能直接改写肿瘤学，尤其是泌尿生殖系统肿瘤领域的临床实践格局？

Jennifer King 教授：在我看来，现有的抗肿瘤治疗药物，已经极大地延长了泌尿生殖系统肿瘤患者的总生存期，越来越多的患者进入了长期生存阶段。因此，未来最有可能改变临床实践的核心方向，主要聚焦于两大维度：一是进一步降低抗肿瘤治疗的相关毒性，在保障抗肿瘤疗效的同时，最大程度减少治疗对患者生活质量的影响；二是全面强化肿瘤生存者的全程护理与长期管理，覆盖患者治疗后康复、远期不良反应管控、心理支持、社会功能恢复等全维度需求，真正实现让患者“活得长、活得好”的肿瘤诊疗最终目标。

Oncology Frontier: Thank you so much for your sharing. Finally, in your opinion, which research breakthrough or development direction is most likely to directly rewrite the clinical practice landscape of oncology, especially genitourinary oncology, in the next few years?

Dr. Jennifer King: In my view, existing anti-tumor therapeutic agents have greatly prolonged the overall survival of patients with genitourinary tumors, and a growing number of patients have entered the long-term survival phase. Therefore, the core directions most likely to change clinical practice in the future mainly focus on two major dimensions: first, to further reduce the toxicities associated with anti-tumor treatment, and minimize the impact of treatment on patients' quality of life while ensuring anti-tumor efficacy; second, to comprehensively strengthen the full-cycle care and long-term management of cancer survivors, covering the full-dimensional needs of patients including post-treatment rehabilitation, management of long-term adverse events, psychological support, and social function recovery, to truly achieve the ultimate goal of cancer diagnosis and treatment: helping patients "live longer and live better".

Jennifer King 教授

美国印第安纳大学医学院