ASCO GU现场直击丨Thomas Powles教授：EV+P方案改写含铂化疗主导格局，重塑尿路上皮癌一线治疗标准

《肿瘤瞭望-泌尿时讯》

对la/mUC患者而言，以铂类为基础的化疗联合方案是数十年来的标准一线治疗方案。结合临床经验，请您分享下该方案的疗效，以及未能满足的患者需求？

Dr. Thomas Powles: Cystectomy was the initial treatment for urothelial cancer. It makes complete sense—cut it out. That’s what we did in the 1940s, 50s, and 60s. Cutting cancers out, and radical cystectomy is a big operation.In the 1980s, when platinum-based chemotherapy was developed, specifically gemcitabine plus cisplatin (Gem-Cis) for urothelial cancer, studies demonstrated that cisplatin-based chemotherapy in the neoadjuvant setting, rather than the adjuvant setting, provided a significant survival advantage.The estimated benefit is an overall 5% improvement in survival.However, about 50% of patients experience cancer relapse. The risk of recurrence depends somewhat on the tumor’s T stage and its aggressiveness.Platinum-based chemotherapy has been shown to significantly reduce the risk of relapse, resulting in an absolute overall survival advantage of about 5%. This means that five-year survival improves from approximately 60% to 65%.The major drawback of chemotherapy is that it is associated with toxicity. It can also delay the time before surgery can take place.For these reasons, some countries and many clinicians have been hesitant to adopt it widely. Gem-Cis remains the standard of care, and although other regimens have been explored, none have proven superior.

《肿瘤瞭望-泌尿时讯》

随着靶免联合方案的发展，维恩妥尤单抗联合帕博利珠单抗等方案显著改善了晚期UC患者生存，您在今年ASCO-GU大会也进行了分享。能否请您结合相关数据，分享下该方案的疗效和安全性？

Dr. Thomas Powles: The enfortumab vedotin and pembrolizumab combination—enfortumab vedotin is a Nectin-4-directed MMAE antibody-drug conjugate (ADC), and pembrolizumab is a PD-1 inhibitor—given together, showed exceptional activity in urothelial cancer. These findings highlight just how much better EV+P is compared to platinum-based chemotherapy. It demonstrated benefits across all subgroups, which underscores the robustness of its efficacy. We know that not all patients respond to EV+P. Around 20% of patients have stable disease, while approximately 5% experience disease progression while on therapy. The fact that EV+P showed superiority across all subgroups further confirms its advantage over chemotherapy. There is ongoing research to identify which patients will derive the greatest benefit from EV+P. Nectin-4 does not appear to be the optimal predictive biomarker. Immunohistochemistry analysis shows that Nectin-4 is broadly overexpressed in most patients. However, I suspect we will find additional biomarkers that can better predict response to EV+P.

A year ago, after only about a year of median follow-up, we showed that enfortumab vedotin and pembrolizumab in the frontline metastatic setting significantly outperformed standard chemotherapy. It doubled progression-free survival and reduced the risk of death by 50%. It was associated with about a 70% response rate. At ASCO-GU, we presented data from a further year of follow-up—so now two years of follow-up—and the results remained consistent. The treatment still doubled progression-free survival and halved the risk of death. The complete response (CR) rate was 30%, which is very high. Overall, about 70% of patients responded to treatment. Among those who responded, the duration of response is striking. Around 50% of patients remained in response at two years, with a median duration of response of two years. Among the patients who achieved a complete response, 75% remained in CR at two years. This represents a transformational shift. When I started working in this field, the median survival for this disease was just one year. Chemotherapy provided temporary benefit, but patients would eventually develop resistance and succumb to the disease. Over the years, working in bladder, kidney, and other tumor types, I have rarely seen such a significant stepwise improvement in treatment outcomes.

《肿瘤瞭望-泌尿时讯》

未来您及团队还将进行哪些探索，以进一步改善晚期UC，以及早期UC患者获益？