Prophylactically administering tocilizumab before bispecific antibody treatment can slash the incidence of cytokine release syndrome (CRS) from ~75% down to 20%. This simple intervention, analogous to using G-CSF for neutropenia, mitigates side effects and makes outpatient administration a much safer and more feasible option for patients.

The future of advanced prostate cancer treatment may involve combining ADCs with bispecific T-cell engagers. This strategy could use ADCs for a short duration to deliver a potent hit, followed by immunotherapy to achieve durable remission, potentially reducing toxicity and enabling earlier use.

Data from a novel Nectin-4 ADC trial showed zero responses in patients with prior topoisomerase therapy. This strongly suggests that payload resistance, not just the ADC target, is a critical mechanism that will dictate future treatment sequencing.

With multiple ADCs available, an emerging sequencing strategy is to alternate between different mechanisms of action, such as following a microtubule toxin-based ADC with a topoisomerase-1 inhibitor payload. This approach aims to avoid compounding specific toxicities, like neuropathy, and potentially circumvent resistance, though it is a strategy born from logic rather than clinical trial data.

Experts are cautious about using ADCs as long-term frontline maintenance therapy in ovarian cancer. Unlike oral PARPs, prolonged administration of these potent chemotherapies could cause cumulative toxicities, especially bone marrow suppression, potentially rendering patients unable to tolerate essential treatments upon relapse.

The SURE-01 trial experienced two early deaths, leading to mandatory dose reductions and growth factor support. While this made the ADC sacituzumab govitecan more manageable, it highlights its narrow therapeutic window and the critical need for proactive toxicity management protocols from the outset.

Initial ADCs targeting PSMA in prostate cancer were hampered by the neurotoxicity of MMAE payloads and inefficient linker technology. This limited deliverable dosage, causing trials to fail for technical reasons rather than a flawed biological target, paving the way for newer, better-designed ADCs.

The failure of the TROPiCS-04 trial for sacituzumab govitecan may not indicate the TROP2 ADC class is ineffective. Experts suggest problems with dosing and toxicity management (e.g., neutropenia) during the trial could be the real culprit, arguing that the drug class still holds promise.

As potent ADCs prove effective, the current paradigm of treating until disease progression is unsustainable due to cumulative toxicity. Experts urge trial designers to be "brave" and prospectively investigate optimal, fixed treatment durations sooner rather than later, shifting the goal from indefinite therapy to achieving a deep remission.