Young-onset colorectal cancer (YOCRC) in the nationwide precision oncology trial IMPRESS-Norway.

Abstract

149 Background: YOCRC, defined as CRC diagnosis before age 50, is rising globally. Driving causes remain incompletely understood. We report interim results from IMPRESS-Norway, focusing on genomic profiles, drug matching rates, and outcomes in YOCRC vs average-onset CRC. Methods: IMPRESS-Norway (NCT04817956) is a prospective, non-randomized, nationwide precision oncology trial. Patients with advanced, inoperable cancers undergo gene panel sequencing (TruSight Oncology 500). Those with actionable alterations are offered matched therapies available within the trial. Primary endpoints include the proportion of screened patients receiving on-trial treatment and disease control rate at 16 weeks. This interim analysis includes all CRC patients enrolled from September 2021 to August 2025. Results: Among 465 CRC patients profiled, median age was 58 years (range, 27-82), 183 (39%) were females, and 218 (47%) had RAS/RAF alterations. Owing to trial priority for young patients, 118 (25%) were YOCRC, among whom 50 (42%) women. Median YOCRC age was 43 years. The age, tumor mutational burden (median 8), and RAS/RAF alteration rates (52%) were comparable between men and women. Of the 118 YOCRC cases, one was microsatellite instable and one had POLE V411L mutation. Ten cases (8%) had mutations that met the criteria for targeted therapies in the IMPRESS-Norway trial, significantly lower than the trial overall average of 16%. Six patients initiated targeted treatment, which included MEK inhibitor for NRAS Q61 alterations (3 patients), immunotherapy (2 patients), and PIK3CA inhibitor (1 patient). Of these, 3 patients achieved stable disease as the best overall response, while another 3 experienced immediate progression. Among the 347 average-onset CRC patients (50 years or older), 52 (15%) possessed actionable biomarkers eligible for the IMPRESS-Norway trial. Of these, 22 began treatment with responses categorized as partial response (3 patients), stable disease (8 patients), or progressive disease (8 patients). Two patients exited the study prior to the first response assessment, while one commenced treatment only recently. Conclusions: The IMPRESS-Norway trial has included a significant number of YOCRC patients, yet these individuals possess fewer actionable biomarkers for targeted therapies compared to the average-onset CRC population. Further research is essential to broaden the treatment options available for YOCRC patients. Clinical trial information: NCT04817956 .