Despite data from kidney cancer showing immunotherapy re-challenge is often ineffective, oncologists admit to using it in urothelial cancer. This highlights a clinical conflict where the desire to use a powerful drug class outweighs the lack of supporting evidence, especially in specific, confusing patient scenarios.
The speakers highlight that negative trials in kidney cancer, which showed no benefit to immunotherapy re-challenge, were "super helpful." This is because they provided definitive evidence to stop a common clinical practice that was not helping patients and potentially causing harm, underscoring the constructive role of well-designed "failed" studies.
The anticipated approval of the highly effective EV-Pembro combination in the perioperative setting will create a new clinical challenge. When these patients eventually relapse years later, clinicians will face a dilemma: re-challenge with the same potent regimen that worked before or switch to older, likely less effective chemotherapies.
Unlike immunotherapy, where re-challenge after progression is dubious, there is an emerging clinical practice of re-challenging patients with the same antibody-drug conjugate (ADC), such as enfortumab vedotin (EV), after a treatment break forced by toxicity. Anecdotally, patients are showing great responses, highlighting a key area for prospective data generation.
Current bladder cancer trials often fail to differentiate between patients with primary resistance (never responded) versus acquired resistance (responded, then progressed). Adopting this distinction, common in lung cancer research, could help identify patient subgroups more likely to benefit from immunotherapy re-challenge and refine trial eligibility criteria.
In a data-free zone, a survey of 78 US oncologists revealed an emerging consensus to wait six months before re-challenging with EV-Pembro after prior immunotherapy. This demonstrates how clinical practice norms can form around arbitrary time points when definitive evidence on optimal treatment-free intervals is lacking.