Andrea Necchi, MD, on the Shifting Role of Chemotherapy in Bladder Cancer

Antibody-drug conjugate (ADC) and immunotherapy combinations are reshaping the treatment landscape for muscle-invasive bladder cancer (MIBC), potentially moving platinum-based chemotherapy out of the first line setting for most patients. Andrea Necchi, MD, professor of medical oncology at Vita-Salute San Raffaele University in Milan, Italy, and director of genitourinary medical oncology at San Raffaele Hospital, discusses this shift and the patient populations in whom chemotherapy may still have a role.

In an interview with Targeted Onc, Necchi explains that ADC-based combinations have demonstrated greater tolerability, more durable responses, and larger survival improvements than regimens built on a chemotherapy backbone. He describes this as a broader treatment trend, with ADC and immunotherapy combinations becoming an increasingly important option for patients with bladder cancer.

Necchi identifies enfortumab vedotin (EV; Padcev) plus pembrolizumab (Keytruda) as his preferred approach when available and approved. He says he sees little rationale for continuing to use chemotherapy in the near future, outside of specific clinical circumstances. Necchi also notes that chemotherapy may instead be considered as salvage treatment for patients whose disease has progressed after prior ADC and immunotherapy exposure. In the current treatment landscape, it also remains an option following EV-pembrolizumab.

One important exception involves tumors with variant histology, particularly those containing a small cell component. Necchi explains that small cell neuroendocrine bladder cancers are more sensitive to platinum-based chemotherapy, making this treatment a potential priority for these patients. He emphasizes that this population has been poorly represented in clinical trials, leaving important gaps in the evidence available to guide treatment selection.

For patients without small cell features, Necchi views ADC and immunotherapy combinations as the leading treatment approach. He also highlights the need to build on these regimens through the development of subsequent treatment combinations, including strategies for patients who require additional therapy after ADC and immunotherapy exposure.