Vignettes explored access to evidence-informed but not universally funded therapies: blinatumomab for low-risk relapse of B-cell acute lymphoblastic leukemia (B-ALL), larotrectinib for TRK-fused soft tissue sarcoma, PBT for unresectable head-and-neck sarcoma, and tisagenlecleucel for first relapse of B-ALL in a patient with Down syndrome. Access to evidence-informed cancer therapies for Canadian children remains variable. Universal funding, simplified approval processes, and the establishment of Canadian PBT centres to reduce travel burden, would ensure timely, equitable access to high-cost therapies.

Knockdown of NTRK1, which encodes TrkA, reduced cell viability and sensitized ATC cells to paclitaxel. Entrectinib was well tolerated at the administered dose, with no significant changes in body weight and serum biochemical markers. Collectively, these findings identify TrkA as a potential therapeutic target in ATC and support further investigation of entrectinib-based combination strategies to improve ATC treatment outcomes.

These findings in rat models and in silico docking indicate that nicardipine increases entrectinib exposure. While these results underscore the risk of significant DDIs, further clinical studies in humans are required to confirm this interaction and determine if entrectinib dose adjustments are necessary to mitigate adverse events.

P2, N=534, Active, not recruiting, Hoffmann-La Roche | Trial completion date: May 2026 --> Jun 2027 | Trial primary completion date: May 2026 --> Jun 2027

No statistically significant difference was observed (P=0.65). This study did not find evidence that baseline PD-L1 expression significantly influences the efficacy of entrectinib in advanced ROS1-rearranged NSCLC patients.

We present the case of a 4-year-old girl with an LMNA-NTRK1 fusion-positive spindle cell neoplasm initially presenting as a subcutaneous nodule adjacent to purpuric patches on the abdomen. This case highlights an atypical cutaneous presentation of NTRK-RSCNs and demonstrates the successful use of larotrectinib, a TRK inhibitor, in achieving both clinical and histological remission.

This analysis illustrates the diversity of NTRK gene fusion partners across various tumor types and highlights the importance of selecting a pan-tumor fusion-partner agnostic test that can identify both known and novel fusion partners to identify patients who may benefit from treatment with TRK inhibitors.

P3, N=68, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Dec 2026 --> Jun 2030

Entrectinib was administered, and an excellent response was observed. This case emphasizes the relevance of performing NGS in cases with unusual clinicopathological findings to identify potential treatment options. Importantly, the morphology deviated from the classic fibrosarcoma-like appearance described in most adult NTRK3-fused neoplasms and broadens the morphological spectrum in which these neoplasms should be considered.

Targeted therapies with TRK inhibitors (TRKi), including larotrectinib and entrectinib, have shown promising efficacy with rapid and durable responses for patients with LGGs and HGGs. Overall, TRKi represent a significant advance for treating NTRK fusion-positive CNS tumors, especially in pediatric populations, offering new hope for patients with limited treatment options. Further studies are required to optimize their use and address unresolved challenges.

P1, N=13, Active, not recruiting, OHSU Knight Cancer Institute | Trial completion date: Jun 2026 --> Dec 2026