Editor's note: The CheckMate 274 study is the first phase 3 clinical trial to obtain positive results in the field of adjuvant immunotherapy for urothelial cancer. It has been previously reported that adjuvant treatment with nivolumab can improve disease-free survival (DFS) in patients with MIBC. At the 2024 European Association of Urology (EAU) annual meeting, Dr. Matthew Galsky from the Icahn School of Medicine at Mount Sinai and Tisch Cancer Institute, USA, reported for the first time the overall survival (OS) results of the CheckMate 274 study.
Dr. Matthew Galsky
Icahn School of Medicine at Mount Sinai
Tisch Cancer Institute
Oncology Frontier：In recent years, research in the field of urothelial cancer has continued to make breakthroughs. Could you please introduce the progress of adjuvant treatment after UC surgery?
Dr. Matthew Galsky: Adjuvant treatment for urothelial cancer, specifically muscle-invasive urothelial cancer, has been a domain of significant challenges and extensive study. The journey began with decades of exploring adjuvant chemotherapy, which, despite its promise, left us without definitive data. A pivotal shift occurred with the advent of adjuvant immune checkpoint blockade, marked by three critical phase three studies: IMvigor010, CheckMate 274, and the AMBASSADOR study. These studies, particularly the AMBASSADOR and CheckMate 274, have illuminated the path forward by demonstrating the efficacy of adjuvant PD-1 blockade in enhancing disease-free survival. However, the journey of discovery continues as we strive to unify these findings into a coherent treatment paradigm.
Oncology Frontier：Previous results of the CheckMate 274 study showed that the DFS, NUTRFS, DMFS and PFS2 of patients with nivolumab adjuvant therapy were improved. So can this benefit be converted to OS?
Dr. Matthew Galsky: The CheckMate 274 study meticulously explored disease-free survival (DFS) as its cornerstone, encompassing a broad spectrum of patients and highlighting the nuanced benefits in those with high PD-L1 expression. While overall survival (OS) emerges as a critical secondary endpoint, its intricate analysis adheres to a hierarchical design, awaiting the fruition of event-driven outcomes. Interim analyses, despite not crossing the statistical significance threshold, have sketched a promising landscape, hinting at a favorable OS trend for patients undergoing adjuvant nivolumab therapy. This evolving narrative, first unveiled at the EAU meeting, offers a glimpse into the potential of converting DFS benefits into tangible OS advancements.
Oncology Frontier：How do you think the adverse events during immunotherapy such as PD-1/PD-L1 inhibitors should be managed to further improve patients’ quality of life?
Dr. Matthew Galsky: The post-operative landscape, particularly after radical interventions for muscle-invasive urothelial cancer, presents a delicate balance between therapeutic efficacy and quality of life considerations. The intersection of prior chemotherapy and surgical trauma underscores the imperative of thoughtful treatment planning. Fortunately, the tolerability profile of immune checkpoint inhibitors offers a conducive avenue for exploration in the adjuvant setting. Nevertheless, vigilance is paramount, especially in light of the 18% incidence rate of significant adverse events in the CheckMate 274 study. Proactive patient education, early symptom identification, and prompt reporting emerge as pivotal strategies in mitigating immune-related adverse effects, ensuring a balanced approach to patient care.
Oncology Frontier：You have been researching in the field of immunotherapy for many years. What other treatment strategies will improve the clinical practice in the field of urothelial cancer in the future?
Dr. Matthew Galsky: The horizon of urothelial cancer treatment is broadening, with a dual focus on exploiting the untapped potential of cellular immunity and delving deeper into the cancer’s intrinsic biology. The quest to modulate myeloid cells, dendritic cells, macrophages, and NK cells holds the promise of unlocking novel anti-tumor responses. Concurrently, there’s a burgeoning interest in translating the rich tapestry of bladder cancer biology into targeted therapies. This dual-pronged approach, leveraging both the tumor microenvironment and cancer cell-specific pathways, heralds a new era of precision medicine in urothelial cancer, promising to refine and enrich our therapeutic arsenal.
