The emergence of positive data from trials like PATINA creates a dilemma for oncologists treating patients who are already stable on an older maintenance therapy. The consensus suggests not altering a successful regimen to avoid disrupting patient stability, revealing a cautious approach to integrating new evidence into established care.

After observing deep, MRD-negative responses at their starting dose, Colonia Therapeutics unconventionally tested a lower dose level. This counter-intuitive strategy aims to identify the minimum effective dose, which is crucial for maximizing the safety profile (the therapeutic window) and improving commercial viability through lower manufacturing costs.

The failure of an adjuvant trial for the TKI pazopanib was likely caused by a protocol change that reduced the dose to manage transaminitis. While well-intentioned to improve tolerability and adherence, the lower dose was sub-therapeutic. This serves as a critical lesson that managing side effects by compromising dose can nullify a drug's potential efficacy.

Due to significant ocular toxicity affecting most patients, the approved starting dose for belantumab is likely not optimal long-term. Effective management requires clinicians to proactively hold, delay, and reduce doses at the first sign of side effects, meaning real-world application will differ from the initial protocol.

Pirtobrutinib is the first BTK inhibitor to show a rate of atrial fibrillation equivalent to a chemoimmunotherapy control arm in a randomized trial. This uniquely safe cardiovascular profile makes it a strong first-line candidate for older Chronic Lymphocytic Leukemia (CLL) patients or those with significant heart-related comorbidities.

The enzalutamide arms saw discontinuation rates of 20-25% due to adverse events. This high rate reflects a different risk calculation for patients who feel healthy and are asymptomatic. Unlike in advanced disease where patients tolerate more toxicity, this population has a very low threshold for side effects, making early intervention a significant trade-off.

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 Phase 2 TRAIT study suggests starting adjuvant abemaciclib at a lower dose and escalating over several weeks significantly reduces early discontinuations due to side effects like diarrhea. This strategy helps more patients get through the initial high-toxicity period and remain on the effective dose for the full two-year course.

A key nuance in managing ponatinib for Ph+ ALL is a response-adapted dosing strategy. Patients are typically started at a 30mg dose, which is then reduced to 15mg once a good minimal residual disease (MRD) response is achieved. This approach aims to maintain efficacy while mitigating long-term toxicity.