In a retrospective observational study of patients diagnosed with neurofibromatosis type 1-associated plexiform neurofibromas, discontinuing targeted MEK inhibitor therapy was associated with less favorable tumor trajectories compared to maintaining continuous treatment. The findings provide empirical insight into post-discontinuation tumor dynamics among individuals receiving selumetinib or luvometinib in routine clinical practice, where the long-term patterns of tumor behavior following the cessation of medication have historically remained unclear despite widespread improvements in disease management.

The investigative team analyzed a real-world clinical cohort comprising forty patients with neurofibromatosis type 1-associated plexiform neurofibromas who had initiated treatment with either selumetinib or luvometinib. To evaluate how treatment continuity impacts clinical course over time, the researchers divided the overall cohort into two distinct groups based on whether patients continued or stopped their prescribed regimens during follow-up, classifying nineteen individuals into the discontinuation cohort and twenty-one individuals into the no-discontinuation cohort.

Patient evaluations and anatomical measurements were systematically structured around a harmonized three-point framework designated as T0, T1, and T2. Across these longitudinal observation intervals, the investigators quantified tumor behavior by tracking dimensional changes in the same predefined target lesion for each participant, ensuring consistent anatomical reference points throughout the monitoring process. Alongside volumetric radiological tracking, patient-reported pain levels were independently documented and evaluated utilizing the Numeric Rating Scale.

Demographic analysis revealed a substantial baseline age disparity between the two study arms. Patients in the discontinuation group were significantly older than their counterparts in the continuous treatment group, presenting with a median age of 24 years compared to a median age of 12 years in the group that remained on therapy, a divergence supported by a statistically significant p-value of 0.0002. This marked demographic divergence and the resulting limited overlap in age distribution between the cohorts formed a central contextual feature of the comparative analysis.

Volumetric evaluations demonstrated divergent tumor growth trajectories between the two cohorts across the T1-to-T2 monitoring interval. In the group that discontinued their MEK inhibitor, the median interval change in tumor volume was positive 7.0 percent, whereas patients who remained on continuous treatment exhibited a median interval change of negative 3.0 percent, a difference that reached statistical significance with a p-value of less than 0.0001. Furthermore, examining trajectories exclusively within the discontinuation group revealed a direct intra-individual transition, shifting from a median tumor volume change of negative 5.0 percent at T1 while receiving therapy to positive 5.0 percent at T2 after treatment was stopped, with this internal reversal yielding a p-value of 0.0003.

To account for baseline demographic confounding, the researchers applied multivariable statistical adjustments. After adjusting for the significant difference in patient age, treatment discontinuation remained independently associated with a 12.27-percentage-point higher tumor volume change across the T1-to-T2 interval, carrying a 95 percent confidence interval spanning from 6.94 to 17.60 percentage points and a p-value of less than 0.001. When the researchers performed an additional adjustment to account for differences in the actual duration of the T1-to-T2 observation window, the association remained present, reflecting a 10.83-percentage-point higher interval tumor volume change with a 95 percent confidence interval of 3.15 to 18.52 percentage points and a p-value of 0.006.

In contrast to the clear volumetric divergence observed in target lesions, symptomatic outcomes related to pain exhibited greater clinical heterogeneity across the study population. When assessing changes recorded on the Numeric Rating Scale over the interval between T1 and T2, the investigators detected no statistically significant difference between patients who discontinued therapy and those who maintained continuous treatment. When examining the specific documentation surrounding why patients stopped therapy, cost-related interruption emerged as the single most frequent recorded factor, accounting for 10 out of the 19 discontinuations, or 52.6 percent of cases.

In their concluding synthesis, the study authors highlighted that cost-related interruption represents an important and tangible practical barrier to sustaining long-term MEK inhibitor therapy in clinical settings. At the same time, the authors explicitly urged caution when interpreting the underlying trajectory data, noting that the retrospective observational nature of the design precludes establishing direct causal inference. They underscored that the substantial age imbalance, the limited overlap in age between groups, and the heterogeneous lengths of the observation intervals represent critical structural limitations that must be carefully considered when evaluating post-discontinuation outcomes in routine care.

Subject of Research: Tumor volume trajectories following MEK inhibitor discontinuation in NF1-associated plexiform neurofibromas

Article Title: Treatment continuity of MEK inhibitors and tumor trajectories after discontinuation in NF1 associated plexiform neurofibromas

Article References: Zhang, L., Wang, K., Cheng, L., Liu, Z., & Wu, H. (2026). Treatment continuity of MEK inhibitors and tumor trajectories after discontinuation in NF1 associated plexiform neurofibromas. Discover Oncology. https://doi.org/10.1007/s12672-026-06300-6

Image Credits: AI Generated

DOI: 10.1007/s12672-026-06300-6

Keywords: neurofibromatosis type 1, plexiform neurofibromas, MEK inhibitors, selumetinib, luvometinib, treatment discontinuation, treatment continuity, tumor volume change, target lesion, Numeric Rating Scale, pain outcomes, cost-related interruption, observational cohort, retrospective study, tumor trajectories, pediatric and adult cohort