Church, Alanna J

Abstract Next-generation sequencing has transformed cancer care by providing essential insights for diagnosis, prognosis, and treatment. However, variability in testing timing, reporting practices, and interpretation challenges limits its clinical impact. This article highlights key opportunities to optimize somatic reporting, emphasizing the importance of timely testing throughout the cancer care continuum to maximize the diagnostic and therapeutic relevance of findings. Technical factors such as test design, sequencing depth, and the use of liquid biopsy substantially influence result accuracy and interpretation, underscoring the need for careful integration with clinical history. Standardized reporting practices that clearly delineate diagnostic, prognostic, and therapeutic findings can enhance the clinical utility of next-generation sequencing results. Streamlined formats and curated clinical trial data further support actionable decision making. Additionally, direct patient engagement and education are essential for empowering patients to navigate genomic testing and make informed decisions about their care. By leveraging multidisciplinary tumor boards, decision-support tools, and emerging artificial intelligence technologies, clinicians can better navigate the complexities of somatic reports. Standardization and clarity in reporting are critical to advancing precision oncology, empowering providers and patients to make informed treatment decisions and improve outcomes.

PURPOSE The TRK inhibitor larotrectinib is US Food and Drug Administration approved for NTRK fusion–positive solid tumors that lack a satisfactory alternative or have progressed after treatment but has not been systematically studied as a frontline therapy with a defined duration of treatment. ADVL1823 evaluated larotrectinib in patients with newly diagnosed NTRK fusion–positive solid tumors with response-adapted duration of therapy and local control. METHODS Patients received larotrectinib twice daily in 28-day cycles for a predefined duration of treatment, ranging from 6 to 26 cycles depending on response to therapy and surgical resectability. The primary end point was the objective response rate (ORR) within six cycles in patients with infantile fibrosarcoma (IFS); patients with other histologic diagnoses were analyzed in a separate cohort. Secondary objectives included event-free survival (EFS) and overall survival (OS). RESULTS Thirty-three patients were enrolled: 18 with IFS and 15 with other solid tumors. The ORR within six cycles was 94% (17/18; 95% adjusted CI, 72.7 to 98.6) among children with IFS and 60% (9/15; 95% CI, 32.3 to 83.7) among children with other solid tumors. Six percent (2/33; 95% CI, 0.7 to 22.2) patients developed progressive disease while on therapy. Two-year EFS and OS among these groups were 82.2% (95% CI, 54.3 to 93.9) and 93.8% (95% CI, 63.2 to 99.1) for IFS and 80% (95% CI, 50.0 to 93.1) and 93.3% (95% CI, 61.3 to 99.0) for other solid tumors, respectively. Patients undergoing surgical resection of their tumor had prolonged EFS, with only 1 of 16 such patients experiencing disease progression. Four of 33 patients had dose-limiting toxicities. CONCLUSION Larotrectinib is highly active in patients with newly diagnosed NTRK fusion–positive solid tumors. Larotrectinib should be a frontline option for patients with IFS and other NTRK fusion–positive solid tumors. Local control with surgical resection remains important in the treatment of patients with IFS.