After years of successfully intensifying hormonal therapy, the focus in prostate cancer is shifting toward de-intensification. Researchers are exploring intermittent therapy for top responders and developing non-hormonal approaches like radioligands to spare patients the chronic, life-altering side effects of permanent castration.

The study utilized "interruption-free survival" as a primary endpoint, a pragmatic measure derived from real-world data. This serves as a valuable surrogate for treatment toxicity, as clinicians typically pause treatment in response to adverse events, providing a quantifiable measure of a drug's real-world tolerability.

Traditional endpoints like progression-free survival (PFS) incentivize continuous treatment. The NCI group proposes "treatment-free survival," a novel metric that quantifies time spent *off* therapy. This endpoint better captures the patient experience and rewards treatments that provide durable responses after a finite course.

Major trials in prostate (PEACE-2), bladder (Keynote B15), and kidney cancer (LITESPARK-022) showcase a common strategy: moving potent systemic therapies into earlier, curative-intent settings. This approach of using the best drugs sooner aims to improve long-term outcomes, though it also raises questions about toxicity and overtreatment.

The development of PARP-1 selective inhibitors like seriparib signals a shift in drug innovation. Instead of only chasing higher efficacy, these new agents aim for a more favorable toxicity profile (less GI toxicity, fewer dose discontinuations) to improve patient quality of life and treatment adherence.

Data on Enfortumab Vedotin suggests that for modern therapies, maintaining patients on treatment longer via a lower, more tolerable starting dose is more important than administering the maximum labeled dose upfront, a concept inherited from the cytotoxic chemotherapy era.

The O11 trial (Len-Belzutafan vs. Cabozantinib) presents the first randomized Phase 3 data for a VEGF/HIF inhibitor combination. Its results will be pivotal in determining if this more toxic doublet approach is justified over monotherapy for IO-refractory kidney cancer, weighing the magnitude of benefit against increased side effects.

Due to soquelitinib's prolonged effect, which 'resets' the immune system long after the drug is cleared, the CEO envisions it as an intermittent therapy. This would move away from the standard daily-for-life treatment model for autoimmune diseases like atopic dermatitis, representing a potential 'holy grail' for treatment.

For the ADC belantamab mafodotin, clinicians should not feel rigidly bound to the initial every-three-week schedule. Data shows that spreading doses out to every 8 or 12 weeks is a viable strategy, as most patients stabilize or even improve their depth of response despite holding the drug, allowing for better toxicity management.