Neurooncología.pósters

Efficacy and safety of erdafitinib in pediatric patients with advanced solid tumors and FGFR alterations in the phase 2 RAGNAR trial

Sat, 01 Jun 2024 00:00:00 GMT

Efficacy and safety of erdafitinib in pediatric patients with advanced solid tumors and FGFR alterations in the phase 2 RAGNAR trial Olaf Witt, Sameer Farouk Sait; Diez, Blanca; Cardoso, Agustín; Reardon, David A.; Welsh, Liam; Shih, Kent C.; Baldini, Capucine; Massard, Christophe; Loriot, Yohann; Pant, Shubham; Sweiti, Hussein; Thomas, Shibu; Hammond, Constance; Najmi, Saltanat; Triantos, Spyros; Crow, Lauren; Geoerger, Birgit Background: Erdafitinib is an oral selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor approved in the US for adult patients (pts) with locally advanced or metastatic urothelial carcinoma with susceptible FGFR3 genetic alterations, as determined by an FDA-approved companion diagnostic test, whose disease has progressed on or after ≥1 line of prior systemic therapy. Primary analysis of the RAGNAR study Broad Panel Cohort demonstrated tumor agnostic efficacy in pts with solid tumors harboring predefined FGFR mutations or fusions (Pant 2023). Here we report on Final Analysis of efficacy and safety results from the Pediatric Cohort of the RAGNAR study. Methods: Pediatric pts ≥6 years with advanced solid tumors and any FGFR mutation, fusion, or tandem duplication received oral erdafitinib. Starting doses were 8 mg, 5 mg, and 3 mg daily for ages > 15 years, 12 to < 15 years, and 6 to < 12 years, respectively, in 21-day cycles with possible individualized up-titration based on serum phosphate and adverse events (AEs). The primary endpoint was objective response rate (ORR) (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 or Response Assessment in Neuro-Oncology [RANO]) by independent review committee (IRC). Secondary endpoints included ORR by investigator, duration of response (DOR), disease control rate (DCR), clinical benefit rate (CBR), progression-free survival (PFS), and overall survival (OS). Results: 11 pts (median age 13 years; range, 6-16; 64% female) received erdafitinib. Median follow-up was 9.7 months at data cutoff. Histologies included low-grade glioma (LGG-6 pts); high-grade glioma (HGG-3 pts); soft tissue sarcoma (1 pt), and temporal neurocytoma (TNEURO-1 pt). 7, 1, and 3 pts had FGFR1, FGFR2,and FGFR3 alterations, respectively. 6, 4, and 1 pts had FGFR fusions, mutations, and tandem duplication, respectively. Pts had a median of 1 prior line of systemic treatment; 6 (55%) had prior radiotherapy. At data cutoff, 1 of 3 pts (33%) with HGG and an FGFR1-TACC1 fusion achieved a partial response based on investigator assessment with a response duration of 19.8 months. Investigator-assessed objective responses were not observed in the other tumor types. DCR and CBR were 100% in pts with LGG and 67% in pts with HGG. Most common treatment-emergent adverse events (TEAEs) included hyperphosphatemia (64%), diarrhea (64%), pain in extremity (45%), alanine transaminase increased (36%), nausea (36%), and onycholysis (27%). No central serous retinopathy events occurred; related serious adverse events (SAEs) occurred in 4 (36%) pts, including 1 SAE of epiphysiolysis; there were no related TEAEs leading to death. Conclusions: In this small pediatric population comprising primarily refractory HGG and LGG with any FGFR alteration, erdafitinib demonstrated limited objective responses but promising disease control with acceptable safety.

Clinical efficacy of a next-generation sequencing (NGS) and immunohistochemistry (IHC) panel in patients with advanced cancer in Argentina.

Wed, 29 May 2024 00:00:00 GMT

Clinical efficacy of a next-generation sequencing (NGS) and immunohistochemistry (IHC) panel in patients with advanced cancer in Argentina. Cantarella, Florencia; Mendoza Bertelli, Andrea; Girotti, Romina; Marino, Ana Clara; Brest, Esteban; Dibarbora, Delfina; Mahmoud, Yamil; Veigas, Florencia; Enrico, Diego Hernan; Tsou, Florencia; Lacava, Juan A.; Piazzoni, Luciano; Riso, Aldo Alejandro; Martinengo, Gastón L.; Rodriguez, Andrés; Beguelin, Zenon; Cerrato, Sebastián; Jerez, Ignacio; Salanova, Rubén Background: The analysis of somatic genomic alterations, evaluation of DNA mismatch repair (MMR) proteins, and examination of PD-L1 expression in tumor biopsies are crucial for prognosis and informed therapeutic decisions. However, their clinical implementation in Argentina faces challenges due to economic costs and lack of evidence. To address this, we conducted a retrospective study to assess the impact of this molecular panel testing on treatment decisions and clinical management of cancer patients in Argentina. Additionally, we evaluated its ability to detect clinically relevant alterations and analyzed the frequency and cooccurrence of mutations in our cohort. Methods: Tumor tissue samples from 266 patients with primary tumors, representing 26 different anatomical sites (53% lung cancer), underwent molecular testing using the Optimus panel developed by Biomakers. The assay integrates somatic sequencing of 52 genes through NGS with IHC assessment ofMMRand PD-L1 proteins. A retrospective evaluation of the clinical effectiveness of the test was conducted on 133 patients. Genomic and clinical data were analyzed usingRwith the pairwise Fisher’s exact test applied for statistical analysis. Results: This panel facilitates molecular characterization, identifying clinically relevant genetic alterations in 65% of patients and detecting deficiency in MMR proteins in 3%. Findings align with global clinical trial availability for identified alterations in 97% of cases. KRAS is the most frequently mutated gene (38%), followed by EGFR (19%), PIK3CA (12%), BRAF (9%), CDK4, and CTNNB1 (5% each), correlating with lung cancer overrepresentation. Simultaneous alterations in EGFR, PIK3CA, CTNNB1, and KIT genes were observed. Pan-tumoral interaction analysis revealed mutual exclusivity between KRAS mutations and those in EGFR, BRAF, CDK4, and CTNNB1. CTNNB1 mutations co-occurred with EGFR mutations, akin to KIT and PDGFRA (p,0.05). The retrospective analysis indicated that the Optimus panel contributed to clinical management of patients in 56% of cases, with 85% detecting clinically relevant variants, aiding treatment definition in 74% of these cases. Conclusions: The Biomakers-developed Optimus panel empowers the molecular characterization of genomic and proteomic biomarkers across tumor types. Its significance in clinical practice lies in contribution to vital decision-making processes, particularly in treatment selection.

6P Extraosseous central nervous system Ewing sarcoma: A single-center retrospective case series

Fri, 01 Mar 2024 00:00:00 GMT

6P Extraosseous central nervous system Ewing sarcoma: A single-center retrospective case series Yorio, Florencia; Arakaki, Naomi; Alessandro, Lucas; Palomar, Nicolás; Diez, Blanca; Muggeri, Alejandro Background Ewing Sarcoma (ES) tumors are malignant tumors mainly affecting pediatric patients. Extra-osseous primary sites are infrequent, being central nervous system (CNS)-ES extremely rare. Diverse differential histological diagnoses for these “small blue round cell” tumors matched to their rareness make diagnosis an arduous challenge. Methods Our single-center retrospective study included patients with cranial CNS-ES and defining molecular features between 10/2007-11/2023. We analyzed clinical presentation, radiologic and histologic features, and median survival. Results Medical records from twenty-four patients were analyzed. The median age was 22 years (range 2-65); 15 adults (>18). Most patients were male (2:1). Headache was the most frequent symptom (35%), followed by seizures, unilateral numbness/weakness, cerebellar syndrome and visual impairments. Findings in brain Magnetic Resonance Imaging; 11 supratentorial lesions, 7 infratentorial and 6 showed diffuse meningeal infiltration. Histopathology showed in most cases conventional diffuse pattern with small round blue cells (n=12). Confirmatory (11;22) translocation was achieved in all cases: 22 confirmed by Protein-Chain-Reaction analysis and 2 by Fluorescence in situ hybridization for EWSR1 gene rearrangement. One case was confirmed by deoxyribonucleic acid (DNA) methylation profiling. Median overall survival (OS) was 78 months (0-140). 21 patients had an OS exceeding 12 months, while 3 patients suffered rapid progression and died within the year of diagnosis. No significant relations were found between treatment and survival. Conclusions Primary CNS-ES is an orphan pathology and its clinical course and treatment options are barely known. In our experience, it is a heterogeneous group in clinical onset, imaging and histopatological findings, treatment response and outcome. Advances in diagnosis technologies such as DNA methylation profiling with subtypes clustering will probably favour further understanding and guide treatment tayloring.