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.

Even when desmoid tumor patients seem to tolerate niragacestat well, they often report a surprising improvement in well-being after discontinuing the drug. This reveals a subtle, cumulative quality-of-life impact from low-grade toxicities that may not be fully appreciated by patients or clinicians during active treatment.

Long-term data from the DEFI trial shows continuing niragasestat beyond one year increases overall response rates from 34% to 46%. Counterintuitively, the incidence and severity of common side effects like diarrhea and nausea tend to diminish after the first year of treatment.

In Phase 1 trials, imaging showed what appeared to be tumor growth months after treatment. This signal, which normally prompts more surgery, was actually a massive immune response. For patients whose doctors waited, this "growth" resolved on its own, leading to positive long-term outcomes.

Patients on niragacestat for desmoid tumors often experience rapid symptom improvement. However, this clinical benefit significantly precedes radiological response (tumor shrinkage on scans), which can take over five months to appear. This disconnect is crucial for managing patient expectations and assessing early treatment efficacy.

While depth of response strongly predicts survival for an individual patient, the FDA analysis concludes it cannot yet be used as a surrogate endpoint to replace overall survival in pivotal clinical trials. It serves as a measure of drug activity, similar to response rate, but is not sufficient for drug approval on its own.

In a neoadjuvant cemiplimab trial, only 6% of patients had a complete response based on radiographic imaging (RECIST criteria), yet 50% achieved a pathologic complete response. This major discrepancy shows clinicians should not rely solely on scans to assess treatment benefit before surgery.

Patients showing a near-complete response at the end of a six-month immunotherapy course may still convert to a full complete response two months later without additional treatment. Clinicians should consider 'holding their nerve' and re-evaluating with repeat imaging before altering the treatment plan.

There is no standard duration for systemic therapies like niragacestat. Clinicians often aim for 6-12 months, potentially extending to two years. The decision to stop is subjective and arbitrary, balancing treatment side effects against disease symptoms, highlighting the need for individualized approaches rather than fixed protocols.