The standard practice of a 6-8 cycle chemotherapy induction followed by maintenance wasn't a deliberate trial design. It evolved organically from patient intolerance to cumulative toxicities like neuropathy, a limitation newer, less toxic drugs like TDXD don't necessarily share.

While precision medicine has focused on tumor biology, this research suggests a broader "precision care" approach is needed. This involves tailoring treatment, such as drug dosage, based on patient-specific factors like physiology, functional reserve, and personal goals, not just genomic markers.

Unlike traditional chemotherapy dosed by body surface area, TKIs for GIST are dosed based on individual patient tolerance. Therapeutic drug monitoring of plasma levels has not proven effective. The standard approach is to start all patients at a recommended dose and then adjust based on side effects to find the highest tolerable dose that maintains efficacy.

Standard RECIST criteria can misclassify a significant response as "stable disease." A desmoid tumor can shrink dramatically in volume (from a "softball" to a "pencil") but maintain its length, showing no change by RECIST. This suggests clinicians are likely underestimating the true benefit of therapies.

The on-body injector's fixed, flat-rate dosage simplifies clinical workflow and improves safety by eliminating the need for constant, error-prone dose recalculations based on patient weight changes, which is standard for many body surface area (BSA)-based cancer therapies.

Chemotherapy is known to worsen metabolic parameters, but this should be viewed as an opportunity, not just a side effect. By actively correcting this metabolic dysfunction with adjunctive therapies, clinicians may be able to enhance the overall life-saving benefit of the chemotherapy itself.

The next frontier in CSCC isn't just about new drugs, but about optimizing existing ones. A key research area is determining the minimum number of immunotherapy doses required for an optimal response—potentially just one or two—to limit toxicity, reduce treatment burden, and personalize care for high-risk patients.

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.

Despite billions invested over 20 years in targeted and genome-based therapies, the real-world benefit to cancer patients has been minimal, helping only a small fraction of the population. This highlights a profound gap and the urgent need for new paradigms like functional precision oncology.