Introduction Muscle-invasive bladder cancer (MIBC) presents unique challenges due to its aggressive nature and the complexity of its treatment. At ESMO Asia 2024, Dr. Brigida Maiorano shared valuable insights into evolving strategies, including bladder-preserving approaches, novel clinical trial designs, and the latest advances in targeted therapies. In this exclusive interview with Oncology Frontier, Dr. Maiorano discusses current standards, promising clinical results, and her vision for improving outcomes in MIBC.Oncology Frontier In the field of muscle-invasive bladder cancer (MIBC), there are still patients who need to preserve their bladder. How do you think treatment strategies should be chosen to meet their needs?
Dr. Brigida Maiorano “Muscle-invasive bladder cancer is a challenging disease with significant implications for treatment and patient quality of life. Currently, the standard of care, for patients eligible for cisplatin, includes neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy. For patients who are ineligible for cisplatin or choose to avoid it, treatment often involves radical cystectomy directly or alternative radical treatments like radiotherapy.
Radical cystectomy, however, is a complex and life-altering procedure. It has considerable impacts on post-surgical management and the patient’s quality of life.
Looking ahead, I believe we must focus on preserving the bladder when possible. This requires careful selection of patients who are suitable candidates for bladder-sparing approaches.
This topic has garnered increasing attention in the scientific and oncological community. For instance, some experts, like Dr. Galsky, have proposed criteria based on achieving a clinical complete response. However, there is still no clear consensus on how to define and measure this response.
To avoid radical cystectomy, we cannot rely solely on histological data, which is often unavailable for such cases. Instead, a combination of tools—radiological evaluation, cystoscopic assessment, and advanced biomarkers like circulating tumor cells and ctDNA—should be utilized.
Future clinical trials must aim to identify patients who can safely avoid radical cystectomy. At San Raffaele Hospital in Milan, we will soon host a consensus meeting with representatives from both academic and regulatory communities to discuss these critical issues and design trials that explore bladder-sparing strategies effectively.”
Oncology Frontier We have entered the era of innovative drug combinations, and drugs like sacituzumab govitecan have shown promising results in studies on MIBC. Could you please share the latest results?
Dr. Brigida Maiorano “Certainly. During this ESMO Asia meeting, we presented updated interim results from the SHER-01 trial. This phase 2, single-arm study evaluates sacituzumab govitecan, an anti-TROP2 antibody-drug conjugate, in patients with cT2-cT4aN0M0 muscle-invasive bladder cancer who are either ineligible for cisplatin or declined its use.
Initially, patients received sacituzumab govitecan at a standard dose of 10 mg/kg, administered over four cycles in the neoadjuvant phase, followed by radical cystectomy. However, after eight patients experienced significant treatment-related adverse events, including one grade 5 event leading to death, we amended the protocol. The dose was reduced to 7.5 mg/kg, and primary prophylaxis with G-CSF was introduced.
These adjustments significantly reduced adverse events, allowing us to proceed with radical cystectomy in 19 patients. Additionally, nine patients, who either achieved a clinical complete response or declined surgery for personal reasons, underwent transurethral resection of the bladder tumor (TURBT) and were included in the efficacy analysis.
The rate of complete pathological responses (defined as ypT0N0) was an encouraging 37.5%. Furthermore, we presented the first analysis of event-free survival (EFS) after a median follow-up of 13 months. The six-month EFS rate was 87.5%, while the one-year EFS stood at 84.4%. These findings highlight the potential of sacituzumab govitecan as a promising neoadjuvant therapy for MIBC.”
Oncology Frontier In the future, what direction will you and your team explore to further improve outcomes for MIBC patients?
Dr. Brigida Maiorano “Our immediate focus is on continuing the SHER-01 trial to gain deeper insights into the efficacy and safety of sacituzumab govitecan.
We have also initiated the SHER-02 trial, which combines sacituzumab govitecan with pembrolizumab during the neoadjuvant phase. Pembrolizumab is then continued in the post-surgical or adjuvant phase. This trial includes a bladder-sparing strategy for patients who achieve a robust response during the neoadjuvant phase.
Our overarching goal is to improve outcomes while minimizing the burden of radical cystectomy. This procedure is highly invasive and profoundly impacts patients’ quality of life. By identifying patients who can safely avoid this surgery and enhancing response rates to neoadjuvant therapies, we aim to improve both survival outcomes and quality of life for MIBC patients.”
Oncology Frontier Could you share your feelings about attending the ESMO Asia conference with the Chinese audience?
Dr. Brigida Maiorano “I was deeply honored to attend this conference, especially as it was my first time in Asia. The experience was overwhelmingly positive. The conference itself was fascinating, and I had the opportunity to meet highly engaged colleagues and thought leaders in oncology. For me, it was a memorable and rewarding experience. Thank you for inviting me.”
This interview highlights Dr. Maiorano’s commitment to advancing treatment strategies for MIBC, focusing on innovative therapies and patient-centric approaches. Her insights reinforce the importance of collaboration and innovation in tackling this challenging disease.
