ALK fusion

Currently, selpercatinib, larotrectinib, and repotrectinib are approved by the FDA for the treatment of certain solid tumors harboring specific gene fusions. Recent studies on zenocutuzumab resulted in the FDA-accelerated approval for NGR1 fusion-positive NSCLC and PDAC. Germline mutations may specifically increase responsiveness to poly(ADP-ribose) polymerase (PARP) inhibitors or platinum-based treatments. Comprehensive genomic profiling, incorporating fusion detection and germline testing, is essential to identify patients who may benefit from precision-based approaches.

P1/2, N=161, Completed, Takeda | N=109 --> 161

While the presence of bone, liver, and adrenal metastasis were independent risk factors for OS. Alectinib is recommended over crizotinib in the treatment of patients with ALK-positive NSCLC.

We report a case of mandibular ssRMS with FUS-TFCP2 fusion treated with the third-generation ALK inhibitor Lorlatinib, resulting in a marked clinical response. We also review the potential utility of ALK-targeted therapies in managing FUS-TFCP2 fusion-positive ssRMS and support further exploration of ALK inhibition in this subset.

Our validation study shows that overly sensitive ALK IHC assays could result in false-positive tumours presenting with difficult-to-read focal or diffusely weak immunoreactivity, which could lead to potential overuse of confirmatory molecular tests. We therefore recommend carefully fine-tuning ALK IHC assays with the D5F3 clone by comparing diagnostic performance with molecular data.

The patient with EML4::ALK fusion was treated with alectinib with partial response...These finding further suggest that SMARCA4d-UT and carcinomas with SMARCA4 loss may be on the same spectrum of disease, and accurate histologic distinction between these lesions may be challenging. A unified terminology may be beneficial for appropriate diagnosis and treatment.

P1/2, N=65, Recruiting, Princess Maxima Center for Pediatric Oncology | Trial completion date: Dec 2030 --> Dec 2033 | Trial primary completion date: Dec 2029 --> Dec 2033

This case highlights the significant efficacy and safety of alectinib in the management of advanced, recurrent, and aggressive UIMT, while also emphasizing the essential role of multidisciplinary management. It provides valuable insights and serves as a reference for the management of similar rare cases.

This includes work that led to the FDA approvals of immune checkpoint inhibitors in multiple rare pediatric tumor types, the NTRK inhibitors larotrectinib, entrectinib, and repotrectinib for children and adults with solid tumors with NTRK fusions, the ALK inhibitor crizotinib in children and adults with ALK-positive inflammatory myofibroblastic tumors, and the radioligand LUATHERA for adolescents and adults with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. Despite these advances, the study of rare pediatric cancers faces multiple challenges including a limited number of patients for efficient and well-powered clinical trials and a dearth of financial incentives. Ongoing, coordinated efforts are needed to continue the advancement of novel treatments and improve survival and minimize late effects.

These alterations were mutually exclusive with common drivers such as EGFR or KRAS. Detection of rare fusions highlights the therapeutic potential of comprehensive NGS profiling in Romanian NSCLC patients.

Atypical-location AFH (e.g., adrenal) exhibits divergent pathologic phenotypes. Diagnosis requires integrated IHC/molecular analysis (e.g., EWSR1 status). Prognostic implications of genetic alterations (e.g., ALK expression) highlight the need for molecular profiling to guide therapy and prognosis.

Initial treatment with chemoimmunotherapy was complicated by hypersensitivity reactions to nivolumab and paclitaxel, leading to a brief hospitalization...This case demonstrates the efficacy of neoadjuvant alectinib in managing ALK-mutant stage III lung adenocarcinoma, highlighting the potential benefits of targeted therapy in the neoadjuvant setting. Further studies are needed to establish optimal treatment protocols for patients with ALK-positive lung cancer.