KEY TAKEAWAYS
- The CAPRI 2-GOIM phase 2 trial aimed to assess the safety and efficacy of cetuximab-based treatment lines in pts with RAS/BRAF V600E WT mCRC.
- The plasma-based NGS profiling feasibly reclassified pts in CAPRI 2-GOIM trial for mCRC resistance mechanisms.
Liquid biopsy is a versatile molecular investive tool for metastatic colorectal cancer (mCRC), whihc assists in the optimal use of anti-epidermal growth factor receptor (EGFR) therapies.
Giulia Martini and the team investigated the safety and efficacy of biomarker-driven, cetuximab-based treatment lines in patients (pts) with RAS/BRAF V600E wild-type (WT) mCRC.
Researchers evaluated the efficacy and safety of cetuximab-based treatment regimens in pts with RAS/BRAF V600E WT mCRCAs confirmed by laboratory testing, a local laboratory testing. The baseline comprehensive next-generation sequencing (NGS) genomic profiling was performed using FoundationOneCDx on tumor tissue and FoundationOneLiquidCDx (324 genes) on plasma circulating tumor DNA (ctDNA).
The treatments included FOLFIRI cetuximab as the first-line (L1), FOLFOX cetuximab for the second-line (L2), and irinotecan cetuximab for the the third-line (L3) in pts with ctDNA RAS/BRAF V600E WT mCRC. For pts with ctDNA RAS/BRAF V600E mutant mCRC, the treatments were FOLFOX bevacizumab for the 2nd line, and regorafenib or trifluridine/tipiracil +/- bevacizumab for the 3rd line.
Results indicated that 240 pts were screened, and a total of 202 were enrolled in the study. The baseline plasma ctDNA results were obtained for all 202 pts, with two having no detectable ctDNA (2/202, 1%). Microsatellite instability-high (MSI-H) profile in 1 patient who received immunotherapy as the L1 treatment.
Of 199 remaining pts, 88% (n=175) had RAS/BRAF WT mCRC while 16 pts had gene alterations in RAS (KRAS/NRAS mutations (n=13) and KRAS amplifications (n=3)). Whereas 8 pts had BRAF alterations (BRAF V600E mutation (n=1) and non-V600E mutations or rearrangements (n=7)).
Mutations were detected in APC (161/199), TP53 (170/199), PI3KCA (31/199), SMAD4 (24/199), ATM (23/199), MAP2K1 (17/199), SOX9 (15/199), FBXW7 (15/199), NF1 (13/199), ERBB2 (13/199), PTEN (12/199), BRCA1 (11/199), ARID1A (11/199), EGFR (8/199), and RNF43 (3/199). Amplifications were observed in EGFR (3/199) and ERBB2 (6/199), while rearrangements occurred in ALK (2/199) and ROS (1/199).
Of 142 pts with having both ctDNA results and tumor tissue, RAS mutations indicated an overall concordance between tissue and ctDNA, with fluctuations observed in 5 cases where mutations were exclusive to tissue and 4 cases exclusive to ctDNA.
They observed amplifications in EGFR (3/199) and ERBB2 (6/199), while rearrangements were seen in ALK (2/199) and ROS (1/199). Among 142 pts with both tumor tissue and ctDNA results, that were consistent with tissue and ctDNA for RAS mutations, except in 5 cases where mutations were observed only in tissue and in 4 cases where mutations were only in ctDNA.
The study concluded that the baseline plasma-based NGS profiling was feasible and reclassified 24/199 (12%) pts in the CAPRI 2-GOIM trial, identifying molecular alterations potentially involved in resistance to anti-EGFR drugs in mCRC.
The trials were sponsored by GRUPPO ONCOLOGICO DELL’ITALIA MERIDIONALE and University of Campania “Luigi Vanvitelli”.
Source: https://cslide.ctimeetingtech.com/esmogi24hybrid/attendee/confcal/show/session/39
Clinical Trials: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-003008-15, https://www.clinicaltrials.gov/study/NCT05312398
Martini G, Troiani T, NapolitanoS, et al. (2024). “Evaluation of plasma assessed comprehensive genomic profiling before first-line treatment with FOLFIRI plus cetuximab in RAS/BRAFV600E wild type metastatic colorectal cancer patients in the CAPRI 2-GOIM trial.” Presented at ESMO-GI, (Abstract 6MO)
