Impact of a molecular tumor board on treatment decisions for advanced solid tumors: Experience from a Portuguese cancer center.

Abstract

e23343 Background: Molecular Tumor Boards (MTB) are pivotal in precision oncology. For patients with advanced solid tumors, after conventional therapeutic options have been exhausted, MTBs comprehensively include molecular profiles in treatment decisions. MTB recommendations may suggest eligibility for clinical trials or treatments that may extend beyond established ESCAT level I–II. This study aims to assess the clinical impact of MTB recommendations on treatment decisions and outcomes in patients with advanced solid tumors (excluding common primary tumors of the lung, thyroid and central nervous system) at our cancer center. Methods: Between February 2020 and June 2024, 197 patients were referred to the MTB. Molecular analysis was done using next-generation sequencing (NGS) with either a 52-gene in-house panel or FoundationOne commercial panel. Additional tests were performed when indicated. Molecular findings, patient characteristics, and treatment decisions were retrospectively analyzed. Statistical analysis was performed using Microsoft Excel and R-Project softwares. Results: Of the 197 referred patients, 146 met the inclusion criteria (excluding those with no actionable molecular alterations per literature, those with known molecular alterations, frail patients, and those with alternative therapeutic options). Molecular analysis was performed on 128 patients; 18 were excluded due to lack of histological material, discontinuation of treatment at our center, or deterioration of their general condition. Among the 128 patients (median age 57 y.o.; 55% female), 64 (50%) had tumors with molecular alterations. Most alterations were found in TP53 (28%), BRAF Non-V600 (17%), KRAS (16%), PIK3CA (14%), and NRAS (9%). Forty-one patients (32%) had actionable targets, and 21 (16%) received treatments based on these findings. ESCAT level III guided most therapeutic proposals. The median number of prior treatment lines was 2 (range 0–6). Clinical benefit was observed in 10 (6%) patients, with 1 complete response (CR) (porocarcinoma TMB-high under pembrolizumab), 3 partial responses (PR) (myofibroblastic tumor, m ROS1, under lorlatinib; neuroblastoma, m ALK , under lorlatinib; melanoma, m BRAF V600E not detected by PCR, under encorafenib/binimetibib), and 6 stable diseases (SD). With a median follow-up of 14 months (95% CI), progression-free survival (PFS) was 3.9 months (95% CI) and overall survival (OS) was 27 months (95% CI). Only 1 case of grade 3 toxicity was observed, requiring temporary treatment suspension. Conclusions: These findings indicate that MTB-guided therapy may enhance clinical outcomes with manageable toxicity in a subset of patients with advanced, refractory malignancies. The study highlights the necessity of further investigation into resistance mechanisms and the incorporation of molecularly guided decisions in earlier treatment lines.